| 小原 知之（おはら ともゆき） | データ更新日：2024.04.10 |
講師 ／
九州大学病院
精神科神経科
医学系学府 病態医学専攻
| 1. | Emi Ueda, Naoki Hirabayashi, Tomoyuki Ohara, Jun Hata, Takanori Honda, Kohta Fujiwara, Yoshihiko Furuta, Mao Shibata, Sawako Hashimoto, Shun Nakamura, Taro Nakazawa, Tomohiro Nakao, Takanari Kitazono, Toshiharu Ninomiya, Koh-Hei Sonoda, Association of Inner Retinal Thickness with Prevalent Dementia and Brain Atrophy in a General Older Population: The Hisayama Study., Ophthalmology science, 10.1016/j.xops.2022.100157, 2, 2, 100157-100157, 2022.06, PURPOSE: To assess the association of inner retinal thickness with prevalent dementia and regional brain atrophy in a general older population of Japanese. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 1078 residents aged 65 years or older who participated in an eye examination, a comprehensive survey of dementia, and brain magnetic resonance imaging scanning in 2017. METHODS: The thicknesses of the inner retinal layers, namely, the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL)-were measured by swept-source OCT (SS-OCT). The association of these retinal thicknesses with the risk of the presence of dementia was estimated using restricted cubic splines and logistic regression models. Regional brain volumes were estimated separately by applying 2 different methods: voxel-based morphometry (VBM) and analysis by FreeSurfer software. The associations of GC-IPL and RNFL thickness with each brain regional volume were analyzed using multiple regression analysis. MAIN OUTCOME MEASURE: Prevalent dementia and regional brain atrophy. RESULTS: Among the study participants, 61 participants (5.7%) were diagnosed with dementia. The likelihood of the presence of dementia significantly increased with lower GC-IPL thickness after adjusting for potential confounders (odds ratio, 1.62 [95% confidence interval, 1.30-2.01] per 1 standard deviation decrement in the GC-IPL thickness), but no significant association was observed with RNFL thickness. In the VBM analyses with the multivariable adjustment, lower GC-IPL thickness was significantly associated with lower volume of known brain regions related to cognitive functions (i.e., the hippocampus, amygdala, entorhinal area, and parahippocampal gyrus) and visual functions (i.e., the cuneus, lingual gyrus, and thalamus). Meanwhile, the volume of the thalamus significantly decreased with lower RNFL thickness, but none of the brain regions related to cognitive function exhibited a volume change in association with RNFL thickness. The sensitivity analysis using FreeSurfer analysis also showed that lower GC-IPL thickness was significantly associated with lower regional brain volume/intracranial volume of the hippocampus, amygdala, cuneus, lingual gyrus, and thalamus. CONCLUSIONS: Our findings suggest that the measurement of GC-IPL thickness by SS-OCT, which is a noninvasive, convenient, and reproducible method, might be useful for identifying high-risk individuals with dementia.. |
| 2. | Taro Nakazawa, Tomoyuki Ohara, Naoki Hirabayashi, Yoshihiko Furuta, Jun Hata, Mao Shibata, Takanori Honda, Takanari Kitazono, Tomohiro Nakao, Toshiharu Ninomiya, Association of white matter lesions and brain atrophy with the development of dementia in a community: the Hisayama Study., Psychiatry and clinical neurosciences, 10.1111/pcn.13533, 77, 6, 330-337, 2023.06, AIM: To investigate the association of white matter lesions volume (WMLV) levels with dementia risk and the association between dementia risk and the combined measures of WMLV and either total brain atrophy or dementia-related gray matter atrophy in a general older population. METHODS: One thousand one hundred fifty-eight Japanese dementia-free community-residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years. WMLV were segmented using the Lesion Segmentation Toolbox. Total brain volume (TBV) and regional gray matter volume were estimated by voxel-based morphometry. The WMLV-to-intracranial brain volume ratio (WMLV/ICV) was calculated, and its association with dementia risk was estimated using Cox proportional hazard models. Total brain atrophy, defined as the TBV-to-ICV ratio (TBV/ICV), and dementia-related regional brain atrophy defined based on our previous report were calculated. The association between dementia risk and the combined measures of WMLV/ICV and either total brain atrophy or the number of atrophied regions was also tested. RESULTS: During the follow-up, 113 participants developed dementia. The risks of dementia increased significantly with higher WMLV/ICV levels. In addition, dementia risk increased additively both in participants with higher WMLV/ICV levels and lower TBV/ICV levels and in those with higher WMLV/ICV levels and a higher number of dementia-related brain regional atrophy. CONCLUSION: The risk of dementia increased significantly with higher WMLV/ICV levels. An additive increment in dementia risk was observed with higher WMLV/ICV levels and lower TBV/ICV levels or a higher number of dementia-related brain regional atrophy, suggesting the importance of prevention or control of cardiovascular risk factors.. |
| 3. | Naoki Hirabayashi, Takanori Honda, Jun Hata, Yoshihiko Furuta, Mao Shibata, Tomoyuki Ohara, Yasuko Tatewaki, Yasuyuki Taki, Shigeyuki Nakaji, Tetsuya Maeda, Kenjiro Ono, Masaru Mimura, Kenji Nakashima, Jun-Ichi Iga, Minoru Takebayashi, Toshiharu Ninomiya, Association Between Frequency of Social Contact and Brain Atrophy in Community-Dwelling Older People Without Dementia: The JPSC-AD Study., Neurology, 2023.07, BACKGROUND AND OBJECTIVES: Epidemiological evidence has shown that social isolation, a low frequency of social contact with others, is associated with the risk of dementia and late-life depressive symptoms. Therefore, we hypothesized that low frequency of social contact may be involved in brain atrophy, and depressive symptoms may play some role in this relationship. We aimed to evaluate the association between low frequency of social contact and the volumes of various brain regions and to assess the extent to which depressive symptoms mediate these relationships from a large population-based multisite cohort study. METHODS: Dementia-free community-dwelling Japanese aged ≥65 years underwent brain MRI scans and a comprehensive health examination. Frequency of contact with non-cohabiting relatives and friends was determined by asking a single question with four categories: everyday, several times a week, several times a month, and seldom. Total and regional brain volumes, intracranial volume (ICV) and white matter lesions volume were estimated using FreeSurfer software. The associations between frequency of social contact and brain volumes per ICV were examined using analyses of covariance. Mediation analyses were conducted to calculate the proportion of the associations explained by depressive symptoms. RESULTS: We included 8,896 participants. The multivariable-adjusted mean of the total brain volume in the group with the lowest frequency of social contact was significantly lower compared to that in the group with the highest frequency (67.3% vs 67.8%), with a significant increasing trend across the groups (p value for trend |
| 4. | Tomoyuki Ohara, Akira Monji, Toshiaki Onitsuka, Toshihiko Maekawa, Yoji Hirano, Shogo Hirano, Sadayuki Hashioka, Takahiro Kato, Ichiro Yoshida, Shigenobu Kanba, Interictal psychosis after stroke with forced normalization [6], Journal of Neuropsychiatry and Clinical Neurosciences, 10.1176/appi.neuropsych.18.4.557, 18, 4, 557-559, 2006.09, [URL]. |
| 5. | Tomoyuki Ohara, Toshiharu Ninomiya, Michiaki Kubo, Yoichiro Hirakawa, Yasufumi Doi, Jun Hata, Toru Iwaki, Shigenobu Kanba, Yutaka Kiyohara, Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese The hisayama study, Journal of the American Geriatrics Society, 10.1111/j.1532-5415.2011.03405.x, 59, 6, 1074-1079, 2011.06, [URL], OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-É4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-É4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-É4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR)=1.81, P=.004; AD: HR=3.42, P<.001 vad: hr="1.08," p=".86)." the area under receiver operating characteristic curve was significantly greater when apoe genotype incorporated into a model with potential risk factors for ad vs other measures of discrimination reclassification improvement: integrated also confirmed this improvement in assessment. conclusion: apoe- allele is factor japanese population. information on improves assessment substantially beyond based factors.. id="gencho_ronbuns10040703" class="qir_handle_link"> |
| 6. | Tomoyuki Ohara, Toshiharu Ninomiya, Michiaki Kubo, Yoichiro Hirakawa, Yasufumi Doi, Jun Hata, Toru Iwaki, Shigenobu Kanba, Yutaka Kiyohara, Apolipoprotein Genotype for Prediction of Alzheimer's Disease in Older Japanese: The Hisayama Study, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 10.1111/j.1532-5415.2011.03405.x, 59, 6, 1074-1079, 2011.06, OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-epsilon 4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-epsilon 4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-e4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR) = 1.81, P = .004; AD: HR = 3.42, P <. vad: hr="1.08," p=".86)." the area under receiver operating characteristic curve was significantly greater when apoe genotype incorporated into a model with potential risk factors for ad vs other measures of discrimination reclassification improvement: integrated also confirmed this improvement in assessment.>CONCLUSION: The APOE-epsilon 4 allele is a risk factor for AD in the Japanese population. Information on APOE genotype improves AD risk assessment substantially beyond a model based on potential risk factors. J Am Geriatr Soc 59:1074-1079, 2011.. |
| 7. | Toshiharu Ninomiya, Tomoyuki Ohara, Yoichiro Hirakawa, Daigo Yoshida, Yasufumi Doi, Jun Hata, Shigenobu Kanba, Toru Iwaki, Yutaka Kiyohara, Midlife and late-life blood pressure and dementia in japanese elderly The hisayama study, Hypertension, 10.1161/HYPERTENSIONAHA.110.163055, 58, 1, 22-28, 2011.07, [URL], The associations between blood pressure and dementia have been inconclusive. We followed up a total of 668 community-dwelling Japanese individuals without dementia, aged 65 to 79 years, for 17 years and examined the associations of late-life and midlife hypertension with the risk of vascular dementia and Alzheimer disease using the Cox proportional hazards model. During the follow-up, 76 subjects experienced vascular dementia and 123 developed Alzheimer disease. The age- and sex-adjusted incidence of vascular dementia significantly increased with elevated late-life blood pressure levels (normal: 2.3, prehypertension: 8.4, stage 1 hypertension: 12.6, and stage 2 hypertension: 18.9 per 1000 person-years; Ptrendtrend=0.88). After adjusting for potential confounding factors, subjects with prehypertension and stage 1 or stage 2 hypertension had 3.0-fold, 4.5-fold, and 5.6-fold greater risk of vascular dementia, respectively, compared with subjects with normal blood pressure. Likewise, there was a positive association of midlife blood pressure levels with the risk of vascular dementia but not with the risk of Alzheimer disease. Compared with those without hypertension in both midlife and late life, subjects with midlife hypertension had an ≈5-fold greater risk of vascular dementia, regardless of late-life blood pressure levels. Our findings suggest that midlife hypertension and late-life hypertension are significant risk factors for the late-life onset of vascular dementia but not for that of Alzheimer disease in a general Japanese population. Midlife hypertension is especially strongly associated with a greater risk of vascular dementia, regardless of late-life blood pressure levels.. |
| 8. | Toshiharu Ninomiya, Tomoyuki Ohara, Yoichiro Hirakawa, Daigo Yoshida, Yasufumi Doi, Jun Hata, Shigenobu Kanba, Toru Iwaki, Yutaka Kiyohara, Midlife and Late-Life Blood Pressure and Dementia in Japanese Elderly The Hisayama Study, HYPERTENSION, 10.1161/HYPERTENSIONAHA.110.163055, 58, 1, 22-U58, 2011.07, The associations between blood pressure and dementia have been inconclusive. We followed up a total of 668 community-dwelling Japanese individuals without dementia, aged 65 to 79 years, for 17 years and examined the associations of late-life and midlife hypertension with the risk of vascular dementia and Alzheimer disease using the Cox proportional hazards model. During the follow-up, 76 subjects experienced vascular dementia and 123 developed Alzheimer disease. The age-and sex-adjusted incidence of vascular dementia significantly increased with elevated late-life blood pressure levels (normal: 2.3, prehypertension: 8.4, stage 1 hypertension: 12.6, and stage 2 hypertension: 18.9 per 1000 person-years; P(trend) |
| 9. | Tomoyuki Ohara, Y. Doi, Toshiharu Ninomiya, Yoichiro Hirakawa, Jun Hata, Toru Iwaki, Shigenobu Kanba, Y. Kiyohara, Glucose tolerance status and risk of dementia in the community The Hisayama Study, Neurology, 10.1212/WNL.0b013e31822f0435, 77, 12, 1126-1134, 2011.09, [URL], Objective: We investigated the association between glucose tolerance status defined by a 75-g oral glucose tolerance test (OGTT) and the development of dementia. Methods: A total of 1,017 community-dwelling dementia-free subjects aged ≥60 years who underwent the OGTT were followed up for 15 years. Outcome measure was clinically diagnosed dementia. Results: The age- and sex-adjusted incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) were significantly higher in subjects with diabetes than in those with normal glucose tolerance. These associations remained robust even after adjustment for confounding factors for all-cause dementia and AD, but not for VaD (all-cause dementia: adjusted hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.19 to 2.53, p = 0.004; AD: adjusted HR = 2.05, 95% CI = 1.18 to 3.57, p = 0.01; VaD: adjusted HR = 1.82, 95% CI = 0.89 to 3.71, p = 0.09). Moreover, the risks of developing all-cause dementia, AD, and VaD significantly increased with elevated 2-hour postload glucose (PG) levels even after adjustment for covariates, but no such associations were observed for fasting plasma glucose (FPG) levels: compared with those with 2-hour PG levels of |
| 10. | T. Ohara, Y. Doi, T. Ninomiya, Y. Hirakawa, J. Hata, T. Iwaki, S. Kanba, Y. Kiyohara, Glucose tolerance status and risk of dementia in the community The Hisayama Study, NEUROLOGY, 77, 12, 1126-1134, 2011.09, Objective: We investigated the association between glucose tolerance status defined by a 75-g oral glucose tolerance test (OGTT) and the development of dementia. Methods: A total of 1,017 community-dwelling dementia-free subjects aged >= 60 years who underwent the OGTT were followed up for 15 years. Outcome measure was clinically diagnosed dementia. Results: The age- and sex-adjusted incidence of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) were significantly higher in subjects with diabetes than in those with normal glucose tolerance. These associations remained robust even after adjustment for confounding factors for all-cause dementia and AD, but not for VaD (all-cause dementia: adjusted hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.19 to 2.53, p = 0.004; AD: adjusted HR = 2.05, 95% CI = 1.18 to 3.57, p = 0.01; VaD: adjusted HR = 1.82, 95% CI = 0.89 to 3.71, p = 0.09). Moreover, the risks of developing all-cause dementia, AD, and VaD significantly increased with elevated 2-hour postload glucose (PG) levels even after adjustment for covariates, but no such associations were observed for fasting plasma glucose (FPG) levels: compared with those with 2-hour PG levels of = 11.1 mmol/L. Conclusions: Our findings suggest that diabetes is a significant risk factor for all-cause dementia, AD, and probably VaD. Moreover, 2-hour PG levels, but not FPG levels, are closely associated with increased risk of all-cause dementia, AD, and VaD. Neurology (R) 2011;77:1126-1134. |
| 11. | Mio Ozawa, Toshiharu Ninomiya, Tomoyuki Ohara, Yoichiro Hirakawa, Yasufumi Doi, Jun Hata, Kazuhiro Uchida, Tomoko Shirota, Takanari Kitazono, Yutaka Kiyohara, Self-reported dietary intake of potassium, calcium, and magnesium and risk of dementia in the Japanese The hisayama study, Journal of the American Geriatrics Society, 10.1111/j.1532-5415.2012.04061.x, 60, 8, 1515-1520, 2012.08, [URL], Objectives To investigate whether higher intake of potassium, calcium, and magnesium reduces the risk of incident dementia. Design Prospective cohort study. Setting The Hisayama Study, in Japan. Participants One thousand eighty-one community-dwelling Japanese individuals without dementia aged 60 and older. Measurements A 70-item semiquantitative food frequency questionnaire was used to assess potassium, calcium, and magnesium intakes. Hazard ratios (HRs) for the development of all-cause dementia and its subtypes were estimated using Cox proportional hazards model. Results During a 17-year follow-up, 303 participants experienced all-cause dementia; of these, 98 had vascular dementia (VaD), and 166 had Alzheimer's disease (AD). The multivariable-adjusted HRs for the development of all-cause dementia were 0.52 (95% confidence interval [CI] = 0.30-0.91), 0.64 (95% CI = 0.41-1.00), and 0.63 (95% CI = 0.40-1.01) for the highest quartiles of potassium, calcium, and magnesium intake, respectively, compared with the corresponding lowest quartiles. Similarly, the HRs for the development of VaD were 0.20 (95% CI = 0.07-0.56), 0.24 (95% CI = 0.11-0.53), and 0.26 (95% CI = 0.11-0.61) for the highest quartiles of potassium, calcium, and magnesium intake, respectively. There was no evidence of a linear association between these mineral intakes and the risk of AD. Conclusion Higher self-reported dietary intakes of potassium, calcium, and magnesium reduce the risk of all-cause dementia, especially VaD, in the general Japanese population.. |
| 12. | Mio Ozawa, Toshiharu Ninomiya, Tomoyuki Ohara, Yoichiro Hirakawa, Yasufumi Doi, Jun Hata, Kazuhiro Uchida, Tomoko Shirota, Takanari Kitazono, Yutaka Kiyohara, Self-Reported Dietary Intake of Potassium, Calcium, and Magnesium and Risk of Dementia in the Japanese: The Hisayama Study, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 10.1111/j.1532-5415.2012.04061.x, 60, 8, 1515-1520, 2012.08, Objectives To investigate whether higher intake of potassium, calcium, and magnesium reduces the risk of incident dementia. Design Prospective cohort study. Setting The Hisayama Study, in Japan. Participants One thousand eighty-one community-dwelling Japanese individuals without dementia aged 60 and older. Measurements A 70-item semiquantitative food frequency questionnaire was used to assess potassium, calcium, and magnesium intakes. Hazard ratios (HRs) for the development of all-cause dementia and its subtypes were estimated using Cox proportional hazards model. Results During a 17-year follow-up, 303 participants experienced all-cause dementia; of these, 98 had vascular dementia (VaD), and 166 had Alzheimer's disease (AD). The multivariable-adjusted HRs for the development of all-cause dementia were 0.52 (95% confidence interval [CI] = 0.300.91), 0.64 (95% CI = 0.411.00), and 0.63 (95% CI = 0.401.01) for the highest quartiles of potassium, calcium, and magnesium intake, respectively, compared with the corresponding lowest quartiles. Similarly, the HRs for the development of VaD were 0.20 (95% CI = 0.070.56), 0.24 (95% CI = 0.110.53), and 0.26 (95% CI = 0.110.61) for the highest quartiles of potassium, calcium, and magnesium intake, respectively. There was no evidence of a linear association between these mineral intakes and the risk of AD. Conclusion Higher self-reported dietary intakes of potassium, calcium, and magnesium reduce the risk of all-cause dementia, especially VaD, in the general Japanese population.. |
| 13. | 小原 知之, 清原 裕, 糖尿病と認知症の疫学 : 久山町研究 (特集 糖尿病患者における認知症 : 基礎と臨床の最新知見) -- (疫学), 糖尿病, 4, 9, 12-20, 2012.08. |
| 14. | Tomoyuki Ohara, Toshiharu Ninomiya, Yoichiro Hirakawa, Kyota Ashikawa, Akira Monji, Yutaka Kiyohara, Shigenobu Kanba, Michiaki Kubo, Association study of susceptibility genes for late-onset Alzheimer's disease in the Japanese population, Psychiatric Genetics, 10.1097/YPG.0b013e3283586215, 22, 6, 290-293, 2012.12, [URL], APOE is an established susceptibility gene for late-onset Alzheimer's disease (LOAD). Recent genome-wide association studies have identified many additional susceptibility genes for LOAD in populations of European descent. However, there is little information on whether or not genetic variants in these genes are associated with other ethnicities. To investigate the association of seven genes identified by genome-wide association studies, we carried out a case-control study using 825 LOAD cases and 2934 controls in the Japanese population. For the APOE gene, APOE-ε4 carriers had a 4.54-fold higher risk than APOE-ε4 noncarriers after adjusting for age and sex (P=4.6×10-27). For other genes, the single-nucleotide polymorphism in the PICALM gene was significantly associated with LOAD (P=0.02, odds ratio=1.23). There was no significant interaction between PICALM and APOE-ε4 carrier status (P for interaction=0.68). Our data indicate that PICALM is also a susceptibility gene for LOAD in the Japanese population.. |
| 15. | Tomoyuki Ohara, Toshiharu Ninomiya, Yoichiro Hirakawa, Kyota Ashikawa, Akira Monji, Yutaka Kiyohara, Shigenobu Kanba, Michiaki Kubo, Association study of susceptibility genes for late-onset Alzheimer's disease in the Japanese population, PSYCHIATRIC GENETICS, 10.1097/YPG.0b013e3283586215, 22, 6, 290-293, 2012.12, APOE is an established susceptibility gene for late-onset Alzheimer's disease (LOAD). Recent genome-wide association studies have identified many additional susceptibility genes for LOAD in populations of European descent. However, there is little information on whether or not genetic variants in these genes are associated with other ethnicities. To investigate the association of seven genes identified by genome-wide association studies, we carried out a case-control study using 825 LOAD cases and 2934 controls in the Japanese population. For the APOE gene, APOE-epsilon 4 carriers had a 4.54-fold higher risk than APOE-epsilon 4 noncarriers after adjusting for age and sex (P = 4.6 x 10(-27)). For other genes, the single-nucleotide polymorphism in the PICALM gene was significantly associated with LOAD (P = 0.02, odds ratio = 1.23). There was no significant interaction between PICALM and APOE-epsilon 4 carrier status (P for interaction = 0.68). Our data indicate that PICALM is also a susceptibility gene for LOAD in the Japanese population. Psychiatr Genet 22:290-293 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.. |
| 16. | Mio Ozawa, Toshiharu Ninomiya, Tomoyuki Ohara, Yasufumi Doi, Kazuhiro Uchida, Tomoko Shirota, Koji Yonemoto, Takanari Kitazono, Yutaka Kiyohara, Dietary patterns and risk of dementia in an elderly Japanese population The hisayama Study1-3, American Journal of Clinical Nutrition, 10.3945/ajcn.112.045575, 97, 5, 1076-1082, 2013.05, [URL], Background: To our knowledge, there are no previous reports that assessed the association between dietary patterns and risk of dementia in Asian populations. Objective: We investigated dietary patterns and their potential association with risk of incident dementia in a general Japanese population. Design: A total of 1006 community-dwelling Japanese subjects without dementia, aged 60-79 y, were followed up for a median of 15 y. The reduced rank regression procedure was used to efficiently determine their dietary patterns. Estimated risk conferred by a particular dietary pattern on the development of dementia was computed by using a Cox proportional hazards model. Results: Seven dietary patterns were extracted; of these, dietary pattern 1 was correlated with high intakes of soybeans and soybean products, vegetables, algae, and milk and dairy products and a low intake of rice. During the follow-up, 271 subjects developed allcause dementia. Of these individuals, 144 subjects had Alzheimer disease (AD), and 88 subjects had vascular dementia (VaD). After adjustment for potential confounders, risks of development of allcause dementia, AD, and VaD were reduced by 0.66 (95% CI: 0.46, 0.95), 0.65 (95% CI: 0.40, 1.06), and 0.45 (95% CI: 0.22, 0.91), respectively, in subjects in the highest quartile of score for dietary pattern 1 compared with subjects in the lowest quartile. Conclusion: Our findings suggest that a higher adherence to a dietary pattern characterized by a high intake of soybeans and soybean products, vegetables, algae, and milk and dairy products and a low intake of rice is associated with reduced risk of dementia in the general Japanese population.. |
| 17. | Mio Ozawa, Toshiharu Ninomiya, Tomoyuki Ohara, Yasufumi Doi, Kazuhiro Uchida, Tomoko Shirota, Koji Yonemoto, Takanari Kitazono, Yutaka Kiyohara, Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama Study, AMERICAN JOURNAL OF CLINICAL NUTRITION, 10.3945/ajcn.112.045575, 97, 5, 1076-1082, 2013.05, Background: To our knowledge, there are no previous reports that assessed the association between dietary patterns and risk of dementia in Asian populations. Objective: We investigated dietary patterns and their potential association with risk of incident dementia in a general Japanese population. Design: A total of 1006 community-dwelling Japanese subjects without dementia, aged 60-79 y, were followed up for a median of 15 y. The reduced rank regression procedure was used to efficiently determine their dietary patterns. Estimated risk conferred by a particular dietary pattern on the development of dementia was computed by using a Cox proportional hazards model. Results: Seven dietary patterns were extracted; of these, dietary pattern 1 was correlated with high intakes of soybeans and soybean products, vegetables, algae, and milk and dairy products and a low intake of rice. During the follow-up, 271 subjects developed all-cause dementia. Of these individuals, 144 subjects had Alzheimer disease (AD), and 88 subjects had vascular dementia (VaD). After adjustment for potential confounders, risks of development of all-cause dementia, AD, and VaD were reduced by 0.66 (95% Cl: 0.46, 0.95), 0.65 (95% Cl: 0.40, 1.06), and 0.45 (95% CI: 0.22, 0.91), respectively, in subjects in the highest quartile of score for dietary pattern 1 compared with subjects in the lowest quartile. Conclusion: Our findings suggest that a higher adherence to a dietary pattern characterized by a high intake of soybeans and soybean products, vegetables, algae, and milk and dairy products and a low intake of rice is associated with reduced risk of dementia in the general Japanese population. Am J Clin Nutr 2013;97:1076-82.. |
| 18. | Shuichi Isomura, Akira Monji, Kensuke Sasaki, Shingo Baba, Toshiaki Onitsuka, Tomoyuki Ohara, Yoshito Mizoguchi, Takahiro Kato, Hideki Horikawa, Yoshihiro Seki, Shigenobu Kanba, FTD with catatonia-like signs that temporarily resolved with zolpidem, Neurology: Clinical Practice, 10.1212/CPJ.0b013e3182a1ba12, 3, 4, 354-357, 2013.08, [URL]. |
| 19. | Atsuko Sekita, Hisatomi Arima, Toshiharu Ninomiya, Tomoyuki Ohara, Yasufumi Doi, Yoichiro Hirakawa, Masayo Fukuhara, Jun Hata, Koji Yonemoto, Yukiko Ga, Takanari Kitazono, Shigenobu Kanba, Yutaka Kiyohara, Elevated depressive symptoms in metabolic syndrome in a general population of Japanese men A cross-sectional study, BMC Public Health, 10.1186/1471-2458-13-862, 13, 1, 2013.09, [URL], Background: Uncertainty still surrounds the association between metabolic syndrome (MetS) and depression. We aimed to evaluate the association between MetS and elevated depressive symptoms in a general Japanese population. Methods. This is a cross-sectional survey of 3,113 community-dwelling individuals aged 40 years or over. MetS was defined according to the joint interim statement. MetS was diagnosed when a subject had three or more of the following components: 1) central obesity (waist circumference ≥90 cm for men, ≥80 cm in for women); 2) elevated blood pressure (≥130/85 mmHg or current use of antihypertensive medication); 3) hypertriglyceridemia (≥1.7 mmol/L); 4) low HDL cholesterol ( |
| 20. | Atsuko Sekita, Hisatomi Arima, Toshiharu Ninomiya, Tomoyuki Ohara, Yasufumi Doi, Yoichiro Hirakawa, Masayo Fukuhara, Jun Hata, Koji Yonemoto, Yukiko Ga, Takanari Kitazono, Shigenobu Kanba, Yutaka Kiyohara, Elevated depressive symptoms in metabolic syndrome in a general population of Japanese men: a cross-sectional study, BMC PUBLIC HEALTH, 10.1186/1471-2458-13-862, 13, 862, 2013.09, Background: Uncertainty still surrounds the association between metabolic syndrome (MetS) and depression. We aimed to evaluate the association between MetS and elevated depressive symptoms in a general Japanese population. Methods: This is a cross-sectional survey of 3,113 community-dwelling individuals aged 40 years or over. MetS was defined according to the joint interim statement. MetS was diagnosed when a subject had three or more of the following components: 1) central obesity (waist circumference >= 90 cm for men, >= 80 cm in for women); 2) elevated blood pressure (>= 130/85 mmHg or current use of antihypertensive medication); 3) hypertriglyceridemia (>= 1.7 mmol/L); 4) low HDL cholesterol (= 5.55 mmol/L or current use of antidiabetic medication). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). The age- and multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using a logistic regression model. Results: Elevated depressive symptoms were observed in 4.3% of male and 6.3% of female participants. In men, the age- adjusted prevalence of elevated depressive symptoms was significantly higher in subjects with MetS than in those without (7.1% versus 3.6%, p = 0.04). The prevalence of elevated depressive symptoms rose progressively as the number of MetS components increased (3.5%, 3.6%, 5.8%, and 9.2% in male subjects with 0-1, 2, 3, and >= 4 components, respectively; p = 0.02 for trend). This association remained significant even after adjustment for age, marital status, history of cardiovascular disease, smoking habit, alcohol intake, and regular exercise. In women, on the other hand, there was no clear association between MetS and depressive symptoms. Conclusions: MetS was associated with elevated depressive symptoms in a general population of Japanese men.. |
| 21. | Hidetaka Arimura, Chiaki Tokunaga, Takashi Yoshiura, Tomoyuki Ohara, Yasuo Yamashita, Fukai Toyofuku, Automated measurement of cerebral cortical thickness based on fuzzy membership map derived from MR images for evaluation of Alzheimer's disease, 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2013 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2013, 10.1109/EMBC.2013.6611198, 7116-7119, 2013.10, [URL], We have proposed an automated method for three-dimensional (3D) measurement of cerebral cortical thicknesses based on fuzzy membership maps derived from magnetic resonance (MR) images for evaluation of Alzheimer's disease (AD). The cerebral cortical thickness was three-dimensionally measured on each cortical surface voxel by using a localized gradient vector trajectory in a fuzzy membership map. The proposed method could be useful for the 3D measurement of the cerebral cortical thickness on individual cortical surface voxels as an atrophy feature in AD.. |
| 22. | Toshiharu Ninomiya, Masaharu Nagata, Jun Hata, Yoichiro Hirakawa, Mio Ozawa, Daigo Yoshida, Tomoyuki Ohara, Hiro Kishimoto, Naoko Mukai, Masayo Fukuhara, Takanari Kitazono, Yutaka Kiyohara, Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease The Hisayama Study, Atherosclerosis, 10.1016/j.atherosclerosis.2013.09.023, 231, 2, 261-267, 2013.12, [URL], Objective: We examined the association between the ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) or the docosahexaenoic acid (DHA)/AA and the development of cardiovascular disease in a general Japanese population. Methods: A total of 3103 community-dwelling Japanese individuals aged ≥40 years were followed up for an average of 5.1 years. Serum EPA/AA ratios were categorized into quartiles. The risk estimates were computed using a Cox proportional hazards model. Results: During the follow-up period, 127 subjects experienced cardiovascular events. Age- and sex-adjusted incidence rates of cardiovascular disease increased with lower serum EPA/AA ratios in individuals with high-sensitivity C-reactive protein (HS-CRP) of ≥1.0mg/L ( p for trend=0.006), whereas no clear association was observed in those with HS-CRP of |
| 23. | Toshiharu Ninomiya, Masaharu Nagata, Jun Hata, Yoichiro Hirakawa, Mio Ozawa, Daigo Yoshida, Tomoyuki Ohara, Hiro Kishimoto, Naoko Mukai, Masayo Fukuhara, Takanari Kitazono, Yutaka Kiyohara, Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: The Hisayama Study, Atherosclerosis, 10.1016/j.atherosclerosis.2013.09.023, 231, 2, 261-267, 2013.12, Objective: We examined the association between the ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) or the docosahexaenoic acid (DHA)/AA and the development of cardiovascular disease in a general Japanese population. Methods: A total of 3103 community-dwelling Japanese individuals aged ≥40 years were followed up for an average of 5.1 years. Serum EPA/AA ratios were categorized into quartiles. The risk estimates were computed using a Cox proportional hazards model. Results: During the follow-up period, 127 subjects experienced cardiovascular events. Age- and sex-adjusted incidence rates of cardiovascular disease increased with lower serum EPA/AA ratios in individuals with high-sensitivity C-reactive protein (HS-CRP) of ≥1.0mg/L ( p for trend=0.006), whereas no clear association was observed in those with HS-CRP of < 1.0mg/L (p for trend=0.27). The multivariable-adjusted risk of cardiovascular disease increased significantly, by 1.52 times (95% confidence interval 1.12-2.04) per 0.20 decrement in serum EPA/AA ratio in subjects with HS-CRP of ≥1.0mg/L. A lower serum EPA/AA ratio was significantly associated with an increased risk of coronary heart disease, but there was no evidence of an association with stroke. The magnitude of the influence of the serum EPA/AA ratio on the cardiovascular risk increased significantly with elevating HS-CRP levels taken as a continuous variable (p for heterogeneity=0.007). However, no such association was observed for DHA/AA ratio. Conclusion: Our findings suggest that a lower serum EPA/AA ratio is associated with a greater risk of cardiovascular disease, especially coronary heart disease, among subjects with higher HS-CRP levels in the general Japanese population. © 2013 Elsevier Ireland Ltd.. |
| 24. | Akira Monji, Keisuke Motomura, Yoshito Mizoguchi, Tomoyuki Ohara, Shingo Baba, Takashi Yoshiura, Shigenobu Kanba, A case of late-onset bipolar disorder with severely abnormal behavior and neuroimaging observations very similar to those of frontotemporal dementia, Journal of Neuropsychiatry and Clinical Neurosciences, 10.1176/appi.neuropsych.13020031, 26, 1, 2014, [URL]. |
| 25. | Masaaki Hokama, Sugako Oka, Julio Leon, Toshiharu Ninomiya, Hiroyuki Honda, Kensuke Sasaki, Toru Iwaki, Tomoyuki Ohara, Tomio Sasaki, Frank M. LaFerla, Yutaka Kiyohara, Yusaku Nakabeppu, Altered expression of diabetes-related genes in Alzheimer's disease brains The Hisayama study, Cerebral Cortex, 10.1093/cercor/bht101, 24, 9, 2476-2488, 2014.01, [URL], Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM.. |
| 26. | Toshiharu Ninomiya, Masaharu Nagata, Jun Hata, Yoichiro Hirakawa, Mio Ozawa, Daigo Yoshida, Tomoyuki Ohara, Hiro Kishimoto, Naoko Mukai, Masayo Fukuhara, Takanari Kitazono, Yutaka Kiyohara, Corrigendum to "Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease The Hisayama Study" [Atherosclerosis 231 (2) (2013) 261-267], Atherosclerosis, 10.1016/j.atherosclerosis.2014.03.033, 234, 2, 344-345, 2014.01, [URL]. |
| 27. | Mio Ozawa, Tomoyuki Ohara, Toshiharu Ninomiya, Jun Hata, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Kazuhiro Uchida, Tomoko Shirota, Takanari Kitazono, Yutaka Kiyohara, Milk and dairy consumption and risk of dementia in an elderly Japanese population The hisayama study, Journal of the American Geriatrics Society, 10.1111/jgs.12887, 62, 7, 1224-1230, 2014.01, [URL], Objectives To determine the effect of milk and dairy intake on the development of all-cause dementia and its subtypes in an elderly Japanese population. Design Prospective cohort study. Setting The Hisayama Study, Japan. Participants Individuals aged 60 and older without dementia (N = 1,081). Measurements Milk and dairy intake was estimated using a 70-item semiquantitative food frequency questionnaire grouped into quartiles. The risk estimates of milk and dairy intake on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were computed using a Cox proportional hazards model. Results Over 17 years of follow-up, 303 subjects developed all-cause dementia; 166 had AD, and 98 had VaD. The age- and sex-adjusted incidence of all-cause dementia, AD, and VaD significantly decreased as milk and dairy intake level increased (P for trend =.03 for all-cause dementia,.04 for AD,.01 for VaD). After adjusting for potential confounders, the linear relationship between milk and dairy intake and development of AD remained significant (P for trend =.03), whereas the relationships with all-cause dementia and VaD were not significant. The risk of AD was significantly lower in the second, third, and fourth quartiles of milk and dairy intake than in the first quartile. Conclusion Greater milk and dairy intake reduced the risk of dementia, especially AD, in the general Japanese population.. |
| 28. | Mio Ozawa, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Response Letter, Journal of the American Geriatrics Society, 10.1111/jgs.13163, 62, 12, 2467-2468, 2014.01, [URL]. |
| 29. | Mio Ozawa, Tomoyuki Ohara, Toshiharu Ninomiya, Jun Hata, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Kazuhiro Uchida, Tomoko Shirota, Takanari Kitazono, Yutaka Kiyohara, Milk and Dairy Consumption and Risk of Dementia in an Elderly Japanese Population: The Hisayama Study, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 10.1111/jgs.12887, 62, 7, 1224-1230, 2014.07, OBJECTIVES: To determine the effect of milk and dairy intake on the development of all-cause dementia and its subtypes in an elderly Japanese population. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, Japan. PARTICIPANTS: Individuals aged 60 and older without dementia (N = 1,081). MEASUREMENTS: Milk and dairy intake was estimated using a 70-item semiquantitative food frequency questionnaire grouped into quartiles. The risk estimates of milk and dairy intake on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were computed using a Cox proportional hazards model. RESULTS: Over 17 years of follow-up, 303 subjects developed all-cause dementia; 166 had AD, and 98 had VaD. The age-and sex-adjusted incidence of all-cause dementia, AD, and VaD significantly decreased as milk and dairy intake level increased (P for trend = .03 for all-cause dementia, .04 for AD, .01 for VaD). After adjusting for potential confounders, the linear relationship between milk and dairy intake and development of AD remained significant (P for trend = .03), whereas the relationships with all-cause dementia and VaD were not significant. The risk of AD was significantly lower in the second, third, and fourth quartiles of milk and dairy intake than in the first quartile. CONCLUSION: Greater milk and dairy intake reduced the risk of dementia, especially AD, in the general Japanese population.. |
| 30. | Masaaki Hokama, Sugako Oka, Julio Leon, Toshiharu Ninomiya, Hiroyuki Honda, Kensuke Sasaki, Toru Iwaki, Tomoyuki Ohara, Tomio Sasaki, Frank M. LaFerla, Yutaka Kiyohara, Yusaku Nakabeppu, Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study, CEREBRAL CORTEX, 10.1093/cercor/bht101, 24, 9, 2476-2488, 2014.09, Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM.. |
| 31. | Mio Ozawa, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, DIETARY FACTORS AND INCIDENCE OF DEMENTIA: COX REGRESSION ANALYSIS WITH SPECIAL EMPHASIS ON THE NUMBER OF EVENTS RESPONSE, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 10.1111/jgs.13163, 62, 12, 2467-2468, 2014.12. |
| 32. | Atsushi Hirano, Tomoyuki Ohara, Atsushi Takahashi, Masayuki Aoki, Yuta Fuyuno, Kyota Ashikawa, Takashi Morihara, Masatoshi Takeda, Kouzin Kamino, Etsuko Oshima, Yuko Okahisa, Nobuto Shibata, Heii Arai, Hiroyasu Akatsu, Masashi Ikeda, Nakao Iwata, Toshiharu Ninomiya, Akira Monji, Takanari Kitazono, Yutaka Kiyohara, Michiaki Kubo, Shigenobu Kanba, A genome-wide association study of late-onset Alzheimer's disease in a Japanese population, Psychiatric Genetics, 10.1097/YPG.0000000000000090, 25, 4, 139-146, 2015.08, [URL], Objective: Although a number of genome-wide association studies (GWASs) of late-onset Alzheimer's disease (LOAD) have been carried out, there have been little GWAS data on East Asian populations. Design: To discover the novel susceptibility loci of LOAD, we carried out a GWAS using 816 LOAD cases and 7992 controls with a replication analysis using an independent panel of 1011 LOAD cases and 7212 controls in a Japanese population. In addition, we carried out a stratified analysis by APOE-ε4 status to eliminate the established effect of APOE region. Results: Our data indicated that 18p11.32 (rs1992269, P =9.77× 10-7), CNTNAP2 (rs802571, P= 1.26×10-6), and 12q24.23 (rs11613092, P =6.85×10-6) were suggestive loci for susceptibility to LOAD. Conclusion: We identified three suggestive loci for susceptibility to LOAD in a Japanese population. Among these, rs802571, located at intron 1 of CNTNAP2, was considered to be a plausible candidate locus from a functional perspective.. |
| 33. | Atsushi Hirano, Tomoyuki Ohara, Atsushi Takahashi, Masayuki Aoki, Yuta Fuyuno, Kyota Ashikawa, Takashi Morihara, Masatoshi Takeda, Kouzin Kamino, Etsuko Oshima, Yuko Okahisa, Nobuto Shibata, Heii Arai, Hiroyasu Akatsu, Masashi Ikeda, Nakao Iwata, Toshiharu Ninomiya, Akira Monji, Takanari Kitazono, Yutaka Kiyohara, Michiaki Kubo, Shigenobu Kanba, A genome-wide association study of late-onset Alzheimer's disease in a Japanese population, PSYCHIATRIC GENETICS, 10.1097/YPG.0000000000000090, 25, 4, 139-146, 2015.08, ObjectiveAlthough a number of genome-wide association studies (GWASs) of late-onset Alzheimer's disease (LOAD) have been carried out, there have been little GWAS data on East Asian populations.DesignTo discover the novel susceptibility loci of LOAD, we carried out a GWAS using 816 LOAD cases and 7992 controls with a replication analysis using an independent panel of 1011 LOAD cases and 7212 controls in a Japanese population. In addition, we carried out a stratified analysis by APOE-epsilon 4 status to eliminate the established effect of APOE region.ResultsOur data indicated that 18p11.32 (rs1992269, P=9.77x10(-7)), CNTNAP2 (rs802571, P=1.26x10(-6)), and 12q24.23 (rs11613092, P=6.85x10(-6)) were suggestive loci for susceptibility to LOAD.ConclusionWe identified three suggestive loci for susceptibility to LOAD in a Japanese population. Among these, rs802571, located at intron 1 of CNTNAP2, was considered to be a plausible candidate locus from a functional perspective.. |
| 34. | Tomoyuki Ohara, Toshiharu Ninomiya, Jun Hata, Mio Ozawa, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Toru Iwaki, Takanari Kitazono, Shigenobu Kanba, Yutaka Kiyohara, Midlife and late-life smoking and risk of dementia in the community The Hisayama study, Journal of the American Geriatrics Society, 10.1111/jgs.13794, 63, 11, 2332-2339, 2015.11, [URL], Objectives To clarify the association between midlife and late-life smoking and risk of dementia. Design Prospective cohort study. Setting The Hisayama Study, Japan. Participants Japanese community-dwellers without dementia aged 65 to 84 (mean age 72) followed for 17 years (1988-2005) (N = 754), 619 of whom had participated in a health examination conducted in 1973-74 (mean age, 57) and were included in the midlife analysis. Measurements The risk estimates of smoking status on the development of dementia were computed using a Cox proportional hazards model. Results During follow-up, 252 subjects developed all-cause dementia; 143 had Alzheimer's disease (AD), and 76 had vascular dementia (VaD). In late life, the multivariable-adjusted risk of all-cause dementia was significantly greater in current smokers than in never smokers; similar associations were seen for all-cause dementia, AD, and VaD in midlife current smokers. Meanwhile, no significant association was observed between past smoking and risk of any type of dementia in late or midlife. Multivariable analysis showed that smokers in midlife and late life had significantly greater risks than lifelong nonsmokers of all-cause dementia (adjusted hazard ratio (aHR) = 2.28, 95% confidence interval (CI) = 1.49-3.49), AD (aHR = 1.98, 95% CI = 1.09-3.61), and VaD (aHR = 2.88, 95% CI = 1.34-6.20). Such associations were not observed for midlife smokers who quit smoking in late life. Conclusion Persistent smoking from mid- to late life is a significant risk factor for dementia and its subtypes in the general Japanese population.. |
| 35. | Tomoyuki Ohara, Toshiharu Ninomiya, Jun Hata, Mio Ozawa, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Toru Iwaki, Takanari Kitazono, Shigenobu Kanba, Yutaka Kiyohara, Midlife and Late-Life Smoking and Risk of Dementia in the Community: The Hisayama Study, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 10.1111/jgs.13794, 63, 11, 2332-2339, 2015.11, ObjectivesTo clarify the association between midlife and late-life smoking and risk of dementia. DesignProspective cohort study. SettingThe Hisayama Study, Japan. ParticipantsJapanese community-dwellers without dementia aged 65 to 84 (mean age 72) followed for 17 years (1988-2005) (N = 754), 619 of whom had participated in a health examination conducted in 1973-74 (mean age, 57) and were included in the midlife analysis. MeasurementsThe risk estimates of smoking status on the development of dementia were computed using a Cox proportional hazards model. ResultsDuring follow-up, 252 subjects developed all-cause dementia; 143 had Alzheimer's disease (AD), and 76 had vascular dementia (VaD). In late life, the multivariable-adjusted risk of all-cause dementia was significantly greater in current smokers than in never smokers; similar associations were seen for all-cause dementia, AD, and VaD in midlife current smokers. Meanwhile, no significant association was observed between past smoking and risk of any type of dementia in late or midlife. Multivariable analysis showed that smokers in midlife and late life had significantly greater risks than lifelong nonsmokers of all-cause dementia (adjusted hazard ratio (aHR) = 2.28, 95% confidence interval (CI) = 1.49-3.49), AD (aHR = 1.98, 95% CI = 1.09-3.61), and VaD (aHR = 2.88, 95% CI = 1.34-6.20). Such associations were not observed for midlife smokers who quit smoking in late life. ConclusionPersistent smoking from mid- to late life is a significant risk factor for dementia and its subtypes in the general Japanese population.. |
| 36. | Fumie Ikeda, Kentaro Shikata, Jun Hata, Masayo Fukuhara, Yoichiro Hirakawa, Tomoyuki Ohara, Naoko Mukai, Masaharu Nagata, Daigo Yoshida, Koji Yonemoto, Motohiro Esaki, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Combination of helicobacter pylori antibody and serum pepsinogen as a good predictive tool of gastric cancer incidence 20-year prospective data from the hisayama study, Journal of Epidemiology, 10.2188/jea. JE20150258, 26, 12, 629-636, 2016.01, [URL], Background: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. Methods: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. Results: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P |
| 37. | Fumie Ikeda, Kentaro Shikata, Jun Hata, Masayo Fukuhara, Yoichiro Hirakawa, Tomoyuki Ohara, Naoko Mukai, Masaharu Nagata, Daigo Yoshida, Koji Yonemoto, Motohiro Esaki, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Combination of helicobacter pylori antibody and serum pepsinogen as a good predictive tool of gastric cancer incidence 20-year prospective data from the hisayama study, Journal of epidemiology, 10.2188/jea.JE20150258, 26, 12, 629-636, 2016.01, [URL], Background: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. Methods: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. Results: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P |
| 38. | Saion Chatterjee, Sanne A.E. Peters, Mark Woodward, Silvia Mejia Arango, G. David Batty, Nigel Beckett, Alexa Beiser, Amy R. Borenstein, Paul K. Crane, Mary Haan, Linda B. Hassing, Kathleen M. Hayden, Yutaka Kiyohara, Eric B. Larson, Chung Yi Li, Toshiharu Ninomiya, Tomoyuki Ohara, Ruth Peters, Tom C. Russ, Sudha Seshadri, Bjørn H. Strand, Rod Walker, Weili Xu, Rachel R. Huxley, Type 2diabetes as a risk factor for dementia in women compared with men A pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia, Diabetes Care, 10.2337/dc15-1588, 39, 2, 300-307, 2016.02, [URL], Objective Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a metaanalysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. Research Design and Methods A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. Results Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetesassociated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P |
| 39. | Saion Chatterjee, Sanne A. E. Peters, Mark Woodward, Silvia Mejia Arango, G. David Batty, Nigel Beckett, Alexa Beiser, Amy R. Borenstein, Paul K. Crane, Mary Haan, Linda B. Hassing, Kathleen M. Hayden, Yutaka Kiyohara, Eric B. Larson, Chung-Yi Li, Toshiharu Ninomiya, Tomoyuki Ohara, Ruth Peters, Tom C. Russ, Sudha Seshadri, Bjorn H. Strand, Rod Walker, Weili Xu, Rachel R. Huxley, Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia, DIABETES CARE, 10.2337/dc15-1588, 39, 2, 300-307, 2016.02, OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a metaanalysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P CONCLUSIONS Individuals with type 2 diabetes are at similar to 60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.. |
| 40. | Hiro Kishimoto, Tomoyuki Ohara, Jun Hata, Toshiharu Ninomiya, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Fumie Ikeda, Masayo Fukuhara, Shuzo Kumagai, Shigenobu Kanba, Takanari Kitazono, Yutaka Kiyohara, The long-term association between physical activity and risk of dementia in the community the Hisayama Study, European Journal of Epidemiology, 10.1007/s10654-016-0125-y, 31, 3, 267-274, 2016.03, [URL], We investigated the long-term influence of physical activity on the risk of dementia in an elderly Japanese population. A total of 803 community-dwelling elderly Japanese individuals without dementia aged ≥65 years were followed prospectively for 17 years. Physically active status was defined as engaging in exercise at least one or more times per week during leisure time, and participants were divided into an active group and an inactive group by the presence or absence of such physical activity. The risk estimates of physical activity on the development of all-cause dementia and its subtypes were computed using a Cox proportional hazards model. During the follow-up, 291 participants developed all-cause dementia. Of these, 165 had Alzheimer’s disease (AD), 93 had vascular dementia (VaD), and 47 had other dementia. Compared with the inactive group, the active group showed significantly lower crude incidence of AD (21.8 vs. 14.2 per 1000 person-years, p = 0.01), but no significant differences were observed for all-cause dementia (35.6 vs. 30.5, p = 0.17), VaD (11.3 vs. 9.8, p = 049), and other dementia (4.6 vs. 7.1, p = 0.15). After adjusting for potential confounders, the relationship between physical activity and risk of AD remained significant (adjusted hazard ratio 0.59, 95 % confidence interval 0.41–0.84, p = 0.003). Our findings suggest that physical activity reduces the long-term risk of dementia, especially AD, in the general Japanese population.. |
| 41. | Hiro Kishimoto, Tomoyuki Ohara, Jun Hata, Toshiharu Ninomiya, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Fumie Ikeda, Masayo Fukuhara, Shuzo Kumagai, Shigenobu Kanba, Takanari Kitazono, Yutaka Kiyohara, The long-term association between physical activity and risk of dementia in the community: the Hisayama Study, EUROPEAN JOURNAL OF EPIDEMIOLOGY, 10.1007/s10654-016-0125-y, 31, 3, 267-274, 2016.03, We investigated the long-term influence of physical activity on the risk of dementia in an elderly Japanese population. A total of 803 community-dwelling elderly Japanese individuals without dementia aged a parts per thousand yen65 years were followed prospectively for 17 years. Physically active status was defined as engaging in exercise at least one or more times per week during leisure time, and participants were divided into an active group and an inactive group by the presence or absence of such physical activity. The risk estimates of physical activity on the development of all-cause dementia and its subtypes were computed using a Cox proportional hazards model. During the follow-up, 291 participants developed all-cause dementia. Of these, 165 had Alzheimer's disease (AD), 93 had vascular dementia (VaD), and 47 had other dementia. Compared with the inactive group, the active group showed significantly lower crude incidence of AD (21.8 vs. 14.2 per 1000 person-years, p = 0.01), but no significant differences were observed for all-cause dementia (35.6 vs. 30.5, p = 0.17), VaD (11.3 vs. 9.8, p = 049), and other dementia (4.6 vs. 7.1, p = 0.15). After adjusting for potential confounders, the relationship between physical activity and risk of AD remained significant (adjusted hazard ratio 0.59, 95 % confidence interval 0.41-0.84, p = 0.003). Our findings suggest that physical activity reduces the long-term risk of dementia, especially AD, in the general Japanese population.. |
| 42. | 小原 知之, 神庭 重信, 認知症の危険因子と防御因子 (特集 認知症の診断と治療 : 最近の進歩), 臨床精神医学, 45, 4, 411-418, 2016.04. |
| 43. | Naoki Hirabayashi, Jun Hata, Tomoyuki Ohara, Naoko Mukai, Masaharu Nagata, Mao Shibata, Seiji Goto, Yoshihiko Furuta, Fumio Yamashita, Kazufumi Yoshihara, Takanari Kitazono, Nobuyuki Sudo, Yutaka Kiyohara, Toshiharu Ninomiya, Elevated 2-Hour Post-load Glucose Levels and Longer Duration of Diabetes Are Risk Factors for Hippocampal Atrophy in Elderly Japanese: The Hisayama Study, DIABETES, 10.2337/dc15-2800, 65, A361-A361, 2016.06. |
| 44. | Tomoyuki Ohara, Epidemiology of diabetes and risk of Dementia, Brain and Nerve, 10.11477/mf.1416200500, 68, 7, 719-727, 2016.07, The association between diabetes and the risk of developing dementia has received much attention in epidemiological studies. An accurate population-based prospective cohort study has been conducted in the elderly population of the town of Hisayama in Japan since 1985 aiming to elucidate the secular trends in the prevalence of dementia and examine risk and protective factors for dementia in the Japanese population. The prevalence of all-cause dementia significantly increased from 1985 to 2012. In regard to subtypes of dementia, a similar trend was observed for Alzheimer's disease (AD). In a prospective study of risk factors for dementia in Hisayama elder residents without dementia, diabetes was identified as a significant risk factor for developing all-cause dementia, especially AD. Moreover, 2-hour post-load glucose levels were closely associated with increased risk of all-cause dementia, AD, and vascular dementia. In a pathological study of Hisayama residents, higher levels of 2-hour post-load glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly associated with increased risk of neuritic plaques. The steep increase in the frequency of diabetes could lead to the increasing trend in the prevalence of dementia, especially AD, in the Japanese elderly.. |
| 45. | Jun Hata, Naoko Mukai, Masaharu Nagata, Tomoyuki Ohara, Daigo Yoshida, Hiro Kishimoto, Mao Shibata, Yoichiro Hirakawa, Motoyoshi Endo, Tetsuro Ago, Takanari Kitazono, Yuichi Oike, Yutaka Kiyohara, Toshiharu Ninomiya, Serum Angiopoietin-Like Protein 2 Is a Novel Risk Factor for Cardiovascular Disease in the Community, Arteriosclerosis, Thrombosis, and Vascular Biology, 10.1161/ATVBAHA.116.307291, 36, 8, 1686-1691, 2016.08, [URL], Objective - Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population. Approach and Results - A total of 3005 community-dwelling Japanese aged ≥40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80-2.04]; Q3, 1.48 [0.95-2.32]; and Q4, 1.85 [1.20-2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C-reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76-1.94]; Q3, 1.38 [0.87-2.17]; and Q4, 1.66 [1.05-2.60]; P=0.02 for trend). Conclusions - Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation.. |
| 46. | Hiroyuki Honda, Kensuke Sasaki, Hideomi Hamasaki, Masahiro Shijo, Sachiko Koyama, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Satoshi Suzuki, Toru Iwaki, Trends in autopsy-verified dementia prevalence over 29 years of the Hisayama study, Neuropathology, 10.1111/neup.12298, 36, 4, 383-387, 2016.08, [URL], We investigated the trends in dementia over the past 29 years in the town of Hisayama, Japan using 1266 autopsy specimens. The Hisayama study is a prospective cohort study of lifestyle-related diseases that was started in 1961. Clinical examination of dementia was started in 1985 with five detailed cross-sectional assessments conducted in 1985, 1992, 1998, 2005 and 2012. To examine the trends in dementia, we divided the 1266 autopsy samples into five groups according to the year of death: I (1986–1991, 257 cases), II (1992–1997, 268 cases), III (1998–2004, 318 cases), IV (2005–2011, 296 cases) and V (2012–2014, 127 cases). The prevalence of all-cause dementia significantly increased over time (28.4% in group I, 22.4% in group II, 32.1% in group III, 30.1% in group IV, 51.2% in group V; P for trend |
| 47. | Jun Hata, Naoko Mukai, Masaharu Nagata, Tomoyuki Ohara, Daigo Yoshida, Hiro Kishimoto, Mao Shibata, Yoichiro Hirakawa, Motoyoshi Endo, Tetsuro Ago, Takanari Kitazono, Yuichi Oike, Yutaka Kiyohara, Toshiharu Ninomiya, Serum Angiopoietin-Like Protein 2 Is a Novel Risk Factor for Cardiovascular Disease in the Community: The Hisayama Study, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 10.1161/ATVBAHA.116.307291, 36, 8, 1686-1691, 2016.08, Objective Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population. Approach and Results A total of 3005 community-dwelling Japanese aged 40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80-2.04]; Q3, 1.48 [0.95-2.32]; and Q4, 1.85 [1.20-2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C-reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76-1.94]; Q3, 1.38 [0.87-2.17]; and Q4, 1.66 [1.05-2.60]; P=0.02 for trend). Conclusions Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation.. |
| 48. | Honda H, Sasaki K, Hamasaki H, Shijo M, Koyama S, Ohara T, Ninomiya T, Kiyohara Y, Suzuki SO, Iwaki T, Trends in autopsy-verified dementia prevalence over 29 years of the Hisayama study., Neuropathology : official journal of the Japanese Society of Neuropathology, 10.1111/neup.12298, 36, 4, 383-387, 2016.08. |
| 49. | Hiroyuki Honda, Kensuke Sasaki, Hideomi Hamasaki, Masahiro Shijo, Sachiko Koyama, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Satoshi O. Suzuki, Toru Iwaki, Trends in autopsy-verified dementia prevalence over 29 years of the Hisayama study, Neuropathology, 10.1111/neup.12298, 36, 4, 383-387, 2016.08. |
| 50. | Naoki Hirabayashi, Jun Hata, Tomoyuki Ohara, Naoko Mukai, Masaharu Nagata, Mao Shibata, Seiji Gotoh, Yoshihiko Furuta, Fumio Yamashita, Kazufumi Yoshihara, Takanari Kitazono, Nobuyuki Sudo, Yutaka Kiyohara, Toshiharu Ninomiya, Association between diabetes and hippocampal atrophy in Elderly Japanese The Hisayama study, Diabetes Care, 10.2337/dc15-2800, 39, 9, 1543-1549, 2016.09, [URL], OBJECTIVE To investigate the association between diabetes and brain or hippocampal atrophy in an elderly population. RESEARCH DESIGN AND METHODS A total of 1,238 community-dwelling Japanese subjects aged ≥65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders. RESULTS Themultivariable-adjustedmean values of the TBV-to-ICV,HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6%vs. 78.2%for the TBV-to-ICV ratio, 0.513%vs. 0.529%for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P |
| 51. | Naoki Hirabayashi, Jun Hata, Tomoyuki Ohara, Naoko Mukai, Masaharu Nagata, Mao Shibata, Seiji Gotoh, Yoshihiko Furuta, Fumio Yamashita, Kazufumi Yoshihara, Takanari Kitazono, Nobuyuki Sudo, Yutaka Kiyohara, Toshiharu Ninomiya, Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study, DIABETES CARE, 10.2337/dc15-2800, 39, 9, 1543-1549, 2016.09, OBJECTIVE To investigate the association between diabetes and brain or hippocampal atrophy in an elderly population. RESEARCH DESIGN AND METHODS A total of 1,238 community-dwelling Japanese subjects aged >= 65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders. RESULTS The multivariable-adjusted mean values of the TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6% vs. 78.2% for the TBV-to-ICV ratio, 0.513% vs. 0.529% for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P CONCLUSIONS Our data suggest that a longer duration of diabetes and elevated 2-h PG levels, a marker of postprandial hyperglycemia, are risk factors for brain atrophy, particularly hippocampal atrophy.. |
| 52. | Fumie Ikeda, Kentaro Shikata, Jun Hata, Masayo Fukuhara, Yoichiro Hirakawa, Tomoyuki Ohara, Naoko Mukai, Masaharu Nagata, Daigo Yoshida, Koji Yonemoto, Motohiro Esaki, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study, JOURNAL OF EPIDEMIOLOGY, 10.2188/jea.JE20150258, 26, 12, 629-636, 2016.12, Background: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. Methods: A total of 2446 Japanese community-dwelling individuals aged >= 40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. Results: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P Conclusions: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.. |
| 53. | Kaoru Umehara, Naoko Mukai, Jun Hata, Yoichiro Hirakawa, Tomoyuki Ohara, Daigo Yoshida, Hiro Kishimoto, Takanari Kitazono, Sumio Hoka, Yutaka Kiyohara, Toshiharu Ninomiya, Association between serum vitamin D and All-Cause and Cause-Specific death in a general Japanese population ― the hisayama study ―, Circulation Journal, 10.1253/circj.CJ-16-0954, 81, 9, 1315-1321, 2017.01, [URL], Background: Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations. Methods and Results: We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)2D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend 2D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) 2 than in those with eGFR ≥60 mL/min/1.73 m2; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04). Conclusions: The findings suggested that a lower serum 1,25(OH)2D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.. |
| 54. | Tomoyuki Ohara, Emi Oishi, Toshiharu Ninomiya, Day-to-day blood pressure variability and dementia, Oncotarget, 10.18632/oncotarget.22993, 8, 70, 114416-114417, 2017.01, [URL]. |
| 55. | Hideomi Hamasaki, Hiroyuki Honda, Tsuyoshi Okamoto, Sachiko Koyama, Satoshi Suzuki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Toru Iwaki, Recent Increases in Hippocampal Tau Pathology in the Aging Japanese Population The Hisayama Study, Journal of Alzheimer's Disease, 10.3233/JAD-160521, 55, 2, 613-624, 2017.01, [URL], Background: The Hisayama study is a prospective cohort study of lifestyle-related diseases that commenced in 1961. Through it, a significant increasing trend in the prevalence of Alzheimer's disease has been observed over the past 18 years. Objectives: We sought to investigate the increases in brain pathology related to Alzheimer's disease using automated MATLAB morphometric analyses for quantifying tau pathology. Methods: We examined a series of autopsied cases from Hisayama residents obtained between 1998 and 2003 (group A: 203 cases), and between 2009 and 2014 (group B: 232 cases). We developed custom software in MATLAB to analyze abnormal tau deposits quantitatively. Specimens were immunostained with both anti-amyloid-β-protein and anti-phosphorylated tau antibodies. Results: Both the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for senile plaques and Braak stage for NFT were higher in group B. Morphometric analyses of the hippocampi also revealed a trend toward increased tau pathology in both men and women over 80 years of age in group B. The increases were also significant when the subjects were examined independently according to high or low CERAD scores and in all levels of AD neuropathologic change according to the National Institute on Aging-Alzheimer's Association guidelines (2012). Conclusion: We revealed a recent trend of increased tauopathy in the older people, which is partly independent of amyloid-β pathology.. |
| 56. | Masaharu Nagata, Jun Hata, Yoichiro Hirakawa, Naoko Mukai, Daigo Yoshida, Tomoyuki Ohara, Hiro Kishimoto, Hiroyuki Kawano, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community The Hisayama Study, Journal of Epidemiology, 10.1016/j.je.2017.01.004, 27, 12, 578-583, 2017.01, [URL], Background: Whether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations. Methods: A total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002-2012). The levels of the serum EPA:AA ratio were categorized into quartiles ( 0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations. Results: During the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend 0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers. Conclusions: These findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population.. |
| 57. | Kenji Takeuchi, Tomoyuki Ohara, Michiko Furuta, Toru Takeshita, Yukie Shibata, Jun Hata, Daigo Yoshida, Yoshihisa Yamashita, Toshiharu Ninomiya, Tooth Loss and Risk of Dementia in the Community the Hisayama Study, Journal of the American Geriatrics Society, 10.1111/jgs.14791, 65, 5, e95-e100, 2017.05, [URL], Objectives: To clarify the effect of tooth loss on development of all-cause dementia and its subtypes in an elderly Japanese population. Design: Prospective cohort study. Setting: The Hisayama Study, Japan. Participants: Community-dwelling Japanese adults without dementia aged 60 and older (N = 1,566) were followed for 5 years (2007–2012). Measurements: Participants were classified into four categories according to baseline number of remaining teeth (≥20, 10–19, 1–9, 0). The risk estimates of the effect of tooth loss on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were computed using a Cox proportional hazards model. Results: During follow-up, 180 (11.5%) subjects developed all-cause dementia; 127 (8.1%) had AD, and 42 (2.7%) had VaD. After adjusting for potential confounders, there was a tendency for the multivariable-adjusted hazard ratio of all-cause dementia to increase with decrease in number of remaining teeth (P for trend =.04). The risk of all-cause dementia was 1.62 times as great in subjects with 10 to 19 teeth, 1.81 times as great in those with one to nine teeth, and 1.63 times as great in those with no teeth as in those with 20 teeth or more. An inverse association was observed between number of remaining teeth and risk of AD (P for trend =.08), but no such association was observed with risk of VaD (P for trend =.20). Conclusion: Tooth loss is associated with an increased risk of all-cause dementia and AD in the Japanese population.. |
| 58. | Tomoyuki Ohara, Jun Hata, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Toru Iwaki, Takanari Kitazono, Shigenobu Kanba, Yutaka Kiyohara, Toshiharu Ninomiya, Trends in dementia prevalence, incidence, and survival rate in a Japanese community, Neurology, 10.1212/WNL.0000000000003932, 88, 20, 1925-1932, 2017.05, [URL], Objective: To investigate secular trends in the prevalence, incidence, and survival rate of dementia in a Japanese elderly population in a comprehensive manner. Methods: Five cross-sectional surveys of dementia were conducted among residents of a Japanese community, aged ≥65 years, in 1985, 1992, 1998, 2005, and 2012. We also established 2 cohorts consisting of the residents of this age group without dementia in 1988 (n = 803) and 2002 (n = 1,231), and each was followed for 10 years. Results: The age-standardized prevalence of all-cause dementia and Alzheimer disease (AD) increased with time (for all-cause dementia: 6.8% in 1985, 4.6% in 1992, 5.3% in 1998, 8.4% in 2005, and 11.3% in 2012, p for trend |
| 59. | Kenji Takeuchi, Tomoyuki Ohara, Michiko Furuta, Toru Takeshita, Yukie Shibata, Jun Hata, Daigo Yoshida, Yoshihisa Yamashita, Toshiharu Ninomiya, Tooth Loss and Risk of Dementia in the Community: the Hisayama Study, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 10.1111/jgs.14791, 65, 5, E95-E100, 2017.05, ObjectivesTo clarify the effect of tooth loss on development of all-cause dementia and its subtypes in an elderly Japanese population. DesignProspective cohort study. SettingThe Hisayama Study, Japan. ParticipantsCommunity-dwelling Japanese adults without dementia aged 60 and older (N=1,566) were followed for 5years (2007-2012). MeasurementsParticipants were classified into four categories according to baseline number of remaining teeth (20, 10-19, 1-9, 0). The risk estimates of the effect of tooth loss on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were computed using a Cox proportional hazards model. ResultsDuring follow-up, 180 (11.5%) subjects developed all-cause dementia; 127 (8.1%) had AD, and 42 (2.7%) had VaD. After adjusting for potential confounders, there was a tendency for the multivariable-adjusted hazard ratio of all-cause dementia to increase with decrease in number of remaining teeth (P for trend=.04). The risk of all-cause dementia was 1.62 times as great in subjects with 10 to 19 teeth, 1.81 times as great in those with one to nine teeth, and 1.63 times as great in those with no teeth as in those with 20 teeth or more. An inverse association was observed between number of remaining teeth and risk of AD (P for trend=.08), but no such association was observed with risk of VaD (P for trend=.20). ConclusionTooth loss is associated with an increased risk of all-cause dementia and AD in the Japanese population.. |
| 60. | Tomoyuki Ohara, Jun Hata, Daigo Yoshida, Naoko Mukai, Masaharu Nagata, Toru Iwaki, Takanari Kitazono, Shigenobu Kanba, Yutaka Kiyohara, Toshiharu Ninomiya, Trends in dementia prevalence, incidence, and survival rate in a Japanese community, NEUROLOGY, 10.1212/WNL.0000000000003932, 88, 20, 1925-1932, 2017.05, Objective: To investigate secular trends in the prevalence, incidence, and survival rate of dementia in a Japanese elderly population in a comprehensive manner. Methods: Five cross-sectional surveys of dementia were conducted among residents of a Japanese community, aged >= 65 years, in 1985, 1992, 1998, 2005, and 2012. We also established 2 cohorts consisting of the residents of this age group without dementia in 1988 (n = 803) and 2002 (n = 1,231), and each was followed for 10 years. Results: The age-standardized prevalence of all-cause dementia and Alzheimer disease (AD) increased with time (for all-cause dementia: 6.8% in 1985, 4.6% in 1992, 5.3% in 1998, 8.4% in 2005, and 11.3% in 2012, p for trend Conclusions: The increased incidence and improved survival rate of AD could have resulted in the steep increase in AD prevalence in the Japanese elderly.. |
| 61. | Mio Ozawa, Daigo Yoshida, Jun Hata, Tomoyuki Ohara, Naoko Mukai, Mao Shibata, Kazuhiro Uchida, Masashi Nagata, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Dietary Protein Intake and Stroke Risk in a General Japanese Population The Hisayama Study, Stroke, 10.1161/STROKEAHA.116.016059, 48, 6, 1478-1486, 2017.06, [URL], Background and Purpose-The influence of dietary protein intake on stroke risk is an area of interest. We investigated the association between dietary protein intake and stroke risk in Japanese, considering sources of protein. Methods-A total of 2400 subjects aged 40 to 79 years were followed up for 19 years. Dietary protein intake was estimated using a 70-item semiquantitative food frequency questionnaire. The risk estimates for incident stroke and its subtypes were calculated using a Cox proportional hazards model. Results-During the follow-up, 254 participants experienced stroke events; of these, 172 had ischemic stroke, and 58 had intracerebral hemorrhage. Higher total protein intake was significantly associated with lower risks of stroke and intracerebral hemorrhage (both P for trend |
| 62. | Yu Tzu Wu, Alexa S. Beiser, Monique M.B. Breteler, Laura Fratiglioni, Catherine Helmer, Hugh C. Hendrie, Hiroyuki Honda, M. Arfan Ikram, Kenneth M. Langa, Antonio Lobo, Fiona E. Matthews, Tomoyuki Ohara, Karine Pérès, Chengxuan Qiu, Sudha Seshadri, Britt Marie Sjölund, Ingmar Skoog, Carol Brayne, The changing prevalence and incidence of dementia over time-current evidence, Nature Reviews Neurology, 10.1038/nrneurol.2017.63, 13, 6, 327-339, 2017.06, [URL], Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.. |
| 63. | Mio Ozawa, Daigo Yoshida, Jun Hata, Tomoyuki Ohara, Naoko Mukai, Mao Shibata, Kazuhiro Uchida, Masashi Nagata, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Dietary Protein Intake and Stroke Risk in a General Japanese Population The Hisayama Study, STROKE, 10.1161/STROKEAHA.116.016059, 48, 6, 1478-+, 2017.06, Background and Purpose-The influence of dietary protein intake on stroke risk is an area of interest. We investigated the association between dietary protein intake and stroke risk in Japanese, considering sources of protein. Methods-A total of 2400 subjects aged 40 to 79 years were followed up for 19 years. Dietary protein intake was estimated using a 70-item semiquantitative food frequency questionnaire. The risk estimates for incident stroke and its subtypes were calculated using a Cox proportional hazards model. Results-During the follow-up, 254 participants experienced stroke events; of these, 172 had ischemic stroke, and 58 had intracerebral hemorrhage. Higher total protein intake was significantly associated with lower risks of stroke and intracerebral hemorrhage (both P for trend Conclusions-Our findings suggest that higher dietary protein intake is associated with a reduced risk of stroke in the general Japanese population.. |
| 64. | Yu-Tzu Wu, Alexa S. Beiser, Monique M. B. Breteler, Laura Fratiglioni, Catherine Helmer, Hugh C. Hendrie, Hiroyuki Honda, M. Arfan Ikram, Kenneth M. Langa, Antonio Lobo, Fiona E. Matthews, Tomoyuki Ohara, Karine Peres, Chengxuan Qiu, Sudha Seshadri, Britt-Marie Sjolund, Ingmar Skoog, Carol Brayne, The changing prevalence and incidence of dementia over time - current evidence (vol 13, pg 327, 2017), NATURE REVIEWS NEUROLOGY, 10.1038/nrneurol.2017.63, 13, 6, 339-339, 2017.06. |
| 65. | Naoko Mukai, Tomoyuki Ohara, Jun Hata, Yoichiro Hirakawa, Daigo Yoshida, Hiro Kishimoto, Masafumi Koga, Udai Nakamura, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Alternative measures of hyperglycemia and risk of Alzheimer's disease in the community The hisayama study, Journal of Clinical Endocrinology and Metabolism, 10.1210/jc.2017-00439, 102, 8, 3002-3010, 2017.08, [URL], Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD). Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years. Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.. |
| 66. | Emi Oishi, Tomoyuki Ohara, Satoko Sakata, Masayo Fukuhara, Jun Hata, Daigo Yoshida, Mao Shibata, Toshio Ohtsubo, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population The Hisayama Study, Circulation, 10.1161/CIRCULATIONAHA.116.025667, 136, 6, 516-525, 2017.08, [URL], Background: Several observational studies have reported that higher visit-to-visit blood pressure variability is a risk factor for cognitive impairment and dementia. However, no studies have investigated the association of day-to-day blood pressure variability assessed by home blood pressure measurement with the development of dementia. Methods: A total of 1674 community-dwelling Japanese elderly without dementia, ≥60 years of age, were followed up for 5 years (2007-2012). Home blood pressure was measured 3 times every morning for a median of 28 days. Day-to-day systolic (SBP) and diastolic blood pressure variabilities, calculated as coefficients of variation (CoV) of home SBP and diastolic blood pressure, were categorized into quartiles. The hazard ratios and their 95% confidence intervals of the CoV levels of home blood pressure on the development of all-cause dementia, vascular dementia (VaD), and Alzheimer disease (AD) were computed with a Cox proportional hazards model. Results: During the follow-up, 194 subjects developed all-cause dementia; of these, 47 had VaD and 134 had AD. The age- A nd sex-adjusted incidences of all-cause dementia, VaD, and AD increased significantly with increasing CoV levels of home SBP (all P for trend |
| 67. | Naoko Mukai, Tomoyuki Ohara, Jun Hata, Yoichiro Hirakawa, Daigo Yoshida, Hiro Kishimoto, Masafumi Koga, Udai Nakamura, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Alternative Measures of Hyperglycemia and Risk of Alzheimer's Disease in the Community: The Hisayama Study, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 10.1210/jc.2017-00439, 102, 8, 3002-3010, 2017.08, Context and Objective: We investigated the associations of hemoglobin A1c (HbA(1c)), glycated albumin (GA), GA/HbA(1c) ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD). Design and Participants: A total of 1187 community-dwelling Japanese subjects aged >= 65 years without dementia were followed up for an average of 4.8 years. Results: The age-and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA(1c) ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA(1c) and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA(1c) ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA(1c) ratio had a higher risk of AD than those with low GA/HbA(1c) ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA(1c), GA, and 1,5-AG, regardless of glucose tolerance status. Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA(1c), GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA(1c) ratio may be a useful biomarker for predicting incident AD.. |
| 68. | Emi Oishi, Tomoyuki Ohara, Satoko Sakata, Masayo Fukuhara, Jun Hata, Daigo Yoshida, Mao Shibata, Toshio Ohtsubo, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population The Hisayama Study, CIRCULATION, 10.1161/CIRCULATIONAHA.116.025667, 136, 6, 516-+, 2017.08, BACKGROUND: Several observational studies have reported that higher visit-to-visit blood pressure variability is a risk factor for cognitive impairment and dementia. However, no studies have investigated the association of day-to-day blood pressure variability assessed by home blood pressure measurement with the development of dementia. METHODS: A total of 1674 community-dwelling Japanese elderly without dementia, >= 60 years of age, were followed up for 5 years (2007-2012). Home blood pressure was measured 3 times every morning for a median of 28 days. Day-to-day systolic (SBP) and diastolic blood pressure variabilities, calculated as coefficients of variation (CoV) of home SBP and diastolic blood pressure, were categorized into quartiles. The hazard ratios and their 95% confidence intervals of the CoV levels of home blood pressure on the development of all-cause dementia, vascular dementia (VaD), and Alzheimer disease (AD) were computed with a Cox proportional hazards model. RESULTS: During the follow-up, 194 subjects developed all-cause dementia; of these, 47 had VaD and 134 had AD. The age-and sexadjusted incidences of all-cause dementia, VaD, and AD increased significantly with increasing CoV levels of home SBP (all P for trend CONCLUSIONS: Our findings suggest that increased day-to-day blood pressure variability is, independently of average home blood pressure, a significant risk factor for the development of all-cause dementia, VaD, and AD in the general elderly Japanese population.. |
| 69. | Kaoru Umehara, Naoko Mukai, Jun Hata, Yoichiro Hirakawa, Tomoyuki Ohara, Daigo Yoshida, Hiro Kishimoto, Takanari Kitazono, Sumio Hoka, Yutaka Kiyohara, Toshiharu Ninomiya, Association Between Serum Vitamin D and All-Cause and Cause-Specific Death in a General Japanese Population - The Hisayama Study -, CIRCULATION JOURNAL, 10.1253/circj.CJ-16-0954, 81, 9, 1315-+, 2017.09, Background: Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations. Methods and Results: We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH) 2D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged >= 40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)(2)D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend Conclusions: The findings suggested that a lower serum 1,25(OH)(2)D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH) 2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.. |
| 70. | Tomoyuki Ohara, Toshiharu Ninomiya, Author response Trends in dementia prevalence, incidence, and survival rate in a Japanese community, Neurology, 10.1212/WNL.0000000000004590, 89, 18, 1930-1931, 2017.10, [URL]. |
| 71. | Tomoyuki Ohara, Toshiharu Ninomiya, AUTHOR RESPONSE: TRENDS IN DEMENTIA PREVALENCE, INCIDENCE, AND SURVIVAL RATE IN A JAPANESE COMMUNITY, NEUROLOGY, 10.1212/WNL.0000000000004590, 89, 18, 1930-1931, 2017.10. |
| 72. | Erika Castillo, Julio Leon, Guianfranco Mazzei, Nona Abolhassani, Naoki Haruyama, Takashi Saito, Takaomi Saido, Masaaki Hokama, Toru Iwaki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Sakumi Kunihiko, Frank M. Laferla, Yusaku Nakabeppu, Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation, Scientific Reports, 10.1038/s41598-017-17999-3, 7, 1, 2017.12, [URL], Alzheimer's disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the Aβ pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App NL-G-F/NL-G-F and 3xTg-AD-H mouse models. Genes commonly altered in App NL-G-F/NL-G-F and human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App NL-G-F/NL-G-F cortex as Aβ amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. The App NL-G-F/NL-G-F cortex also had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2, Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aβ amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD.. |
| 73. | Erika Castillo, Julio Leon, Guianfranco Mazzei, Nona Abolhassani, Naoki Haruyama, Takashi Saito, Takaomi Saido, Masaaki Hokama, Toru Iwaki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Kunihiko Sakumi, Frank M. LaFerla, Yusaku Nakabeppu, Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation, SCIENTIFIC REPORTS, 10.1038/s41598-017-17999-3, 7, 1, 17762, 2017.12, Alzheimer's disease (AD) is the most common form of dementia, characterized by accumulation of amyloid beta (A beta) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the A beta pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App(NL-GF/NL-G-F) and 3xTg-AD-H mouse models. Genes commonly altered in App(NL-GF/NL-G-F) and human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App(NL-GF/NL-G-F) cortex as A beta amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. The App(NL-G-F/NL-G-F) cortex also had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2 , Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical A beta amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD.. |
| 74. | Nagata M, Hata J, Hirakawa Y, Mukai N, Yoshida D, Ohara T, Kishimoto H, Kawano H, Kitazono T, Kiyohara Y, Ninomiya T, The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community: The Hisayama Study., Journal of epidemiology, 10.1016/j.je.2017.01.004, 27, 12, 578-583, 2017.12. |
| 75. | Keita Takae, Jun Hata, Tomoyuki Ohara, Daigo Yoshida, Mao Shibata, Naoko Mukai, Yoichiro Hirakawa, Hiro Kishimoto, Kazuhiko Tsuruya, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Albuminuria increases the risks for both Alzheimer disease and vascular dementia in community-dwelling Japanese elderly The hisayama study, Journal of the American Heart Association, 10.1161/JAHA.117.006693, 7, 2, 2018.01, [URL], Background--Epidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD). Methods and Results--A total of 1562 community-dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all-cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin-creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow-up, 358 subjects developed all-cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable-adjusted risks of all-cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78-1.60], 1.65 [1.18-2.30], and 1.56 [1.11-2.19] for UACR of ≤6.9, 7.0-12.7, 12.8-29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77-1.86], 1.75 [1.16-2.64], and 1.58 [1.03-2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46-2.29], 1.94 [0.96-3.95], and 2.19 [1.09-4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of 2 had 3.3-fold greater risk of VaD than those with UACR 2. Conclusions--Albuminuria is a significant risk factor for the development of both AD and VaD in community-dwelling Japanese elderly. Moreover, albuminuria and low eGFR are mutually associated with a greater risk of VaD.. |
| 76. | Keita Takae, Jun Hata, Tomoyuki Ohara, Daigo Yoshida, Mao Shibata, Naoko Mukai, Yoichiro Hirakawa, Hiro Kishimoto, Kazuhiko Tsuruya, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Albuminuria increases the risks for both Alzheimer disease and vascular dementia in community-dwelling Japanese elderly: The hisayama study, Journal of the American Heart Association, 10.1161/JAHA.117.006693, 7, 2, 2018.01, Background--Epidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD). Methods and Results--A total of 1562 community-dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all-cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin-creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow-up, 358 subjects developed all-cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable-adjusted risks of all-cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78-1.60], 1.65 [1.18-2.30], and 1.56 [1.11-2.19] for UACR of ≤6.9, 7.0-12.7, 12.8-29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77-1.86], 1.75 [1.16-2.64], and 1.58 [1.03-2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46-2.29], 1.94 [0.96-3.95], and 2.19 [1.09-4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of < 60 mL/min per 1.73 m2 had 3.3-fold greater risk of VaD than those with UACR < 12.8 mg/g and eGFR of ≥60 mL/min per 1.73 m2. Conclusions--Albuminuria is a significant risk factor for the development of both AD and VaD in community-dwelling Japanese elderly. Moreover, albuminuria and low eGFR are mutually associated with a greater risk of VaD.. |
| 77. | Kiyoshi Sanada, Randi Chen, Bradley Willcox, Tomoyuki Ohara, Aida Wen, Cody Takenaka, Kamal Masaki, Association of sarcopenic obesity predicted by anthropometric measurements and 24-y all-cause mortality in elderly men The Kuakini Honolulu Heart Program, Nutrition, 10.1016/j.nut.2017.09.003, 46, 97-102, 2018.02, [URL], Objective The aim of this study was to investigate the association between anthropometric measurements of sarcopenic obesity and all-cause mortality. Methods The study included 2309 Japanese-American men ages 71 to 93 y. Mortality data were available for up to 24 y of follow-up. Sarcopenic obesity defined by three patterns of obesity indexes (body mass index [BMI], percent body fat [%BF] and waist circumference [WC]) and skeletal muscle index estimated by anthropometric measurements. Results Of the 2309 participants, 2210 deaths were reported during the mean follow-up period of 11.7 y. Risk for death was significantly increased with sarcopenia after adjusting for baseline age, lifestyle variables, hypertension, diabetes, and cognitive scores (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15–1.38). Risk for death was significantly decreased with obesity using WC and %BF to define obesity, but not BMI. Risk for death also was significantly increased in the sarcopenia group compared with the optimal group, regardless of which pattern of obesity indexes (BMI, %BF, and WC) was used. Risk for death was significantly increased in sarcopenic obesity defined by WC (HR, 1.19; 95% CI, 1.02–1.38), borderline in the BMI-defined group, and not significant in the %BF-defined group. Conclusion All-cause mortality was increased in men with sarcopenic obesity defined by WC, but not BMI and %BF. Sarcopenia was a stronger predictor of all-cause mortality in this cohort >70 y of age. These results suggest that anthropometric definitions for sarcopenia and sarcopenic obesity are clinically useful as a predictor of all-cause mortality.. |
| 78. | Kiyoshi Sanada, Randi Chen, Bradley Willcox, Tomoyuki Ohara, Aida Wen, Cody Takenaka, Kamal Masaki, Association of sarcopenic obesity predicted by anthropometric measurements and 24-y all-cause mortality in elderly men: The Kuakini Honolulu Heart Program, Nutrition, 10.1016/j.nut.2017.09.003, 46, 97-102, 2018.02, Objective The aim of this study was to investigate the association between anthropometric measurements of sarcopenic obesity and all-cause mortality. Methods The study included 2309 Japanese-American men ages 71 to 93 y. Mortality data were available for up to 24 y of follow-up. Sarcopenic obesity defined by three patterns of obesity indexes (body mass index [BMI], percent body fat [%BF] and waist circumference [WC]) and skeletal muscle index estimated by anthropometric measurements. Results Of the 2309 participants, 2210 deaths were reported during the mean follow-up period of 11.7 y. Risk for death was significantly increased with sarcopenia after adjusting for baseline age, lifestyle variables, hypertension, diabetes, and cognitive scores (hazard ratio [HR], 1.26 95% confidence interval [CI], 1.15–1.38). Risk for death was significantly decreased with obesity using WC and %BF to define obesity, but not BMI. Risk for death also was significantly increased in the sarcopenia group compared with the optimal group, regardless of which pattern of obesity indexes (BMI, %BF, and WC) was used. Risk for death was significantly increased in sarcopenic obesity defined by WC (HR, 1.19 95% CI, 1.02–1.38), borderline in the BMI-defined group, and not significant in the %BF-defined group. Conclusion All-cause mortality was increased in men with sarcopenic obesity defined by WC, but not BMI and %BF. Sarcopenia was a stronger predictor of all-cause mortality in this cohort > 70 y of age. These results suggest that anthropometric definitions for sarcopenia and sarcopenic obesity are clinically useful as a predictor of all-cause mortality.. |
| 79. | 向井 直子, 秦 淳, 平川 洋一郎, 小原 知之, 吉田 大悟, 中村 宇大, 北園 孝成, 二宮 利治, 地域住民における糖尿病有病率の時代的変化、1988-2012年 久山町研究, 糖尿病, 61, Suppl.1, S-376, 2018.04. |
| 80. | Masahiro Iida, Fumie Ikeda, Jun Hata, Yoichiro Hirakawa, Tomoyuki Ohara, Naoko Mukai, Daigo Yoshida, Koji Yonemoto, Motohiro Esaki, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Development and validation of a risk assessment tool for gastric cancer in a general Japanese population, Gastric Cancer, 10.1007/s10120-017-0768-8, 21, 3, 383-390, 2018.05, [URL], Background: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. Methods: A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer–Lemeshow test in the validation cohort. Results: During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend |
| 81. | Masahiro Iida, Fumie Ikeda, Jun Hata, Yoichiro Hirakawa, Tomoyuki Ohara, Naoko Mukai, Daigo Yoshida, Koji Yonemoto, Motohiro Esaki, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Development and validation of a risk assessment tool for gastric cancer in a general Japanese population, Gastric Cancer, 10.1007/s10120-017-0768-8, 21, 3, 383-390, 2018.05, Background: There have been very few reports of risk score models for the development of gastric cancer. The aim of this study was to develop and validate a risk assessment tool for discerning future gastric cancer risk in Japanese. Methods: A total of 2444 subjects aged 40 years or over were followed up for 14 years from 1988 (derivation cohort), and 3204 subjects of the same age group were followed up for 5 years from 2002 (validation cohort). The weighting (risk score) of each risk factor for predicting future gastric cancer in the risk assessment tool was determined based on the coefficients of a Cox proportional hazards model in the derivation cohort. The goodness of fit of the established risk assessment tool was assessed using the c-statistic and the Hosmer–Lemeshow test in the validation cohort. Results: During the follow-up, gastric cancer developed in 90 subjects in the derivation cohort and 35 subjects in the validation cohort. In the derivation cohort, the risk prediction model for gastric cancer was established using significant risk factors: age, sex, the combination of Helicobacter pylori antibody and pepsinogen status, hemoglobin A1c level, and smoking status. The incidence of gastric cancer increased significantly as the sum of risk scores increased (P trend < 0.001). The risk assessment tool was validated internally and showed good discrimination (c-statistic = 0.76) and calibration (Hosmer–Lemeshow test P = 0.43) in the validation cohort. Conclusions: We developed a risk assessment tool for gastric cancer that provides a useful guide for stratifying an individual’s risk of future gastric cancer.. |
| 82. | Tomohiro Yubi, Jun Hata, Tomoyuki Ohara, Naoko Mukai, Yoichiro Hirakawa, Daigo Yoshida, Seiji Gotoh, Naoki Hirabayashi, Yoshihiko Furuta, Tetsuro Ago, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Prevalence of and risk factors for cerebral microbleeds in a general Japanese elderly community, Neurology: Clinical Practice, 10.1212/CPJ.0000000000000464, 8, 3, 223-231, 2018.06, [URL], Background We investigated the prevalence of and risk factors for cerebral microbleeds (CMBs) in a cross-sectional study of a general population of Japanese elderly. Methods In 2012, brain MRI scanning at 1.5T and comprehensive health examination were conducted for 1281 residents aged 65 years or older. CMBs were defined as ovoid hypointensity lesions less than 10 mm in diameter on T2-weighted images and classified into deep/infratentorial or lobar CMBs. Age- and sex-specific and overall prevalence of CMBs were estimated, and the associations of traditional cardiovascular risk factors and APOE polymorphism with the presence of CMBs were examined using a logistic regression analysis. Results The crude prevalences of total, deep/infratentorial, and lobar CMBs were 18.7% (n = 240), 13.5% (n = 173), and 9.6% (n = 123), respectively. The prevalence of total CMBs was 23.0% in men and 15.5% in women and increased with aging in both sexes (both p for trend |
| 83. | Yubi T, Hata J, Ohara T, Mukai N, Hirakawa Y, Yoshida D, Gotoh S, Hirabayashi N, Furuta Y, Ago T, Kitazono T, Kiyohara Y, Ninomiya T, Prevalence of and risk factors for cerebral microbleeds in a general Japanese elderly community., Neurology. Clinical practice, 10.1212/CPJ.0000000000000464, 8, 3, 223-231, 2018.06. |
| 84. | Yumi Yamaguchi-Kabata, Takashi Morihara, Tomoyuki Ohara, Toshiharu Ninomiya, Atsushi Takahashi, Hiroyasu Akatsu, Yoshio Hashizume, Noriyuki Hayashi, Daichi Shigemizu, Keith A. Boroevich, Manabu Ikeda, Michiaki Kubo, Masatoshi Takeda, Tatsuhiko Tsunoda, Integrated analysis of human genetic association study and mouse transcriptome suggests LBH and SHF genes as novel susceptible genes for amyloid-β accumulation in Alzheimer’s disease, Human Genetics, 10.1007/s00439-018-1906-z, 137, 6-7, 521-533, 2018.07, [URL], Alzheimer’s disease (AD) is a common neurological disease that causes dementia in humans. Although the reports of associated pathological genes have been increasing, the molecular mechanism leading to the accumulation of amyloid-β (Aβ) in human brain is still not well understood. To identify novel genes that cause accumulation of Aβ in AD patients, we conducted an integrative analysis by combining a human genetic association study and transcriptome analysis in mouse brain. First, we examined genome-wide gene expression levels in the hippocampus, comparing them to amyloid Aβ level in mice with mixed genetic backgrounds. Next, based on a GWAS statistics obtained by a previous study with human AD subjects, we obtained gene-based statistics from the SNP-based statistics. We combined p values from the two types of analysis across orthologous gene pairs in human and mouse into one p value for each gene to evaluate AD susceptibility. As a result, we found five genes with significant p values in this integrated analysis among the 373 genes analyzed. We also examined the gene expression level of these five genes in the hippocampus of independent human AD cases and control subjects. Two genes, LBH and SHF, showed lower expression levels in AD cases than control subjects. This is consistent with the gene expression levels of both the genes in mouse which were negatively correlated with Aβ accumulation. These results, obtained from the integrative approach, suggest that LBH and SHF are associated with the AD pathogenesis.. |
| 85. | Yamaguchi-Kabata Y, Morihara T, Ohara T, Ninomiya T, Takahashi A, Akatsu H, Hashizume Y, Hayashi N, Shigemizu D, Boroevich KA, Ikeda M, Kubo M, Takeda M, Tsunoda T, Integrated analysis of human genetic association study and mouse transcriptome suggests LBH and SHF genes as novel susceptible genes for amyloid-β accumulation in Alzheimer's disease., Human genetics, 10.1007/s00439-018-1906-z, 2018.07. |
| 86. | Mao Shibata, Tomoyuki Ohara, Daigo Yoshida, Jun Hata, Naoko Mukai, Hiroyuki Kawano, Shigenobu Kanba, Takanari Kitazono, Toshiharu Ninomiya, Association between the ratio of serum arachidonic acid to eicosapentaenoic acid and the presence of depressive symptoms in a general Japanese population the Hisayama Study, Journal of Affective Disorders, 10.1016/j.jad.2018.05.004, 237, 73-79, 2018.09, [URL], Background: Epidemiological evidence suggests that fish consumption and intake of n-3 polyunsaturated fatty acids (PUFA)—namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—confer protection against depression. However, few studies have addressed the influence of the balance between n-3 PUFA and n-6 PUFA in the human body on depression. Methods: A total of 2,529 community-dwelling Japanese residents aged ≥ 40 years were assessed for depressive symptoms (defined as a score of 16 points or more on the Center for Epidemiologic Studies Depression Scale [CES-D]) in 2007. The serum arachidonic acid (AA) /EPA ratio and AA/DHA ratio were measured in frozen samples collected in 2002 and categorized into quartiles. The odds ratios (ORs) for the presence of depressive symptoms were calculated using a logistic regression model. Results: The prevalence of depressive symptoms was 4.3%. There was no significant association between either the serum AA/EPA ratio or AA/DHA ratio and the presence of depressive symptoms. However, subjects with the highest serum AA/EPA ratios (range: 3.28–13.3) had a 4.10 times (95%CI: 1.13–19.80) greater OR for the presence of depressive symptoms than those with the lowest ratios (0.30–1.65) after adjusting for confounding factors in the subgroup with high-sensitivity C-reactive protein (hs-CRP) ≥ 1.0 mg/L, while no clear association was observed in the subgroup with hs-CRP |
| 87. | Mao Shibata, Tomoyuki Ohara, Daigo Yoshida, Jun Hata, Naoko Mukai, Hiroyuki Kawano, Shigenobu Kanba, Takanari Kitazono, Toshiharu Ninomiya, Association between the ratio of serum arachidonic acid to eicosapentaenoic acid and the presence of depressive symptoms in a general Japanese population: the Hisayama Study, Journal of Affective Disorders, 10.1016/j.jad.2018.05.004, 237, 73-79, 2018.09, Background: Epidemiological evidence suggests that fish consumption and intake of n-3 polyunsaturated fatty acids (PUFA)—namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—confer protection against depression. However, few studies have addressed the influence of the balance between n-3 PUFA and n-6 PUFA in the human body on depression. Methods: A total of 2,529 community-dwelling Japanese residents aged ≥ 40 years were assessed for depressive symptoms (defined as a score of 16 points or more on the Center for Epidemiologic Studies Depression Scale [CES-D]) in 2007. The serum arachidonic acid (AA) /EPA ratio and AA/DHA ratio were measured in frozen samples collected in 2002 and categorized into quartiles. The odds ratios (ORs) for the presence of depressive symptoms were calculated using a logistic regression model. Results: The prevalence of depressive symptoms was 4.3%. There was no significant association between either the serum AA/EPA ratio or AA/DHA ratio and the presence of depressive symptoms. However, subjects with the highest serum AA/EPA ratios (range: 3.28–13.3) had a 4.10 times (95%CI: 1.13–19.80) greater OR for the presence of depressive symptoms than those with the lowest ratios (0.30–1.65) after adjusting for confounding factors in the subgroup with high-sensitivity C-reactive protein (hs-CRP) ≥ 1.0 mg/L, while no clear association was observed in the subgroup with hs-CRP < 1.0 mg/L. Limitations: Reverse causality is possible due to the cross-sectional study design. Conclusions: Our findings suggest that a higher serum AA/EPA ratio is associated with a greater likelihood of depressive symptoms in subjects with systemic inflammation in the general Japanese population.. |
| 88. | Tomoyuki Ohara, Takanori Honda, Jun Hata, Daigo Yoshida, Naoko Mukai, Yoichiro Hirakawa, Mao Shibata, Hiro Kishimoto, Takanari Kitazono, Shigenobu Kanba, Toshiharu Ninomiya, Association Between Daily Sleep Duration and Risk of Dementia and Mortality in a Japanese Community, Journal of the American Geriatrics Society, 10.1111/jgs.15446, 66, 10, 1911-1918, 2018.10, [URL], Objectives: To investigate the association between daily sleep duration and risk of dementia and death in a Japanese elderly population. Design: Prospective cohort study. Setting: The Hisayama Study, Japan. Participants: Community-dwelling Japanese individuals aged 60 and older without dementia. Measurements: Self-reported daily sleep duration was grouped into 5 categories ( |
| 89. | Phillip J. Tully, Deborah A. Turnbull, Kaarin J. Anstey, Nigel Beckett, Alexa S. Beiser, Jonathan Birns, Adam M. Brickman, Nicholas R. Burns, Suzanne Cosh, Peter W. De Leeuw, Diana Dorstyn, Merrill F. Elias, J. Wouter Jukema, Kazuomi Kario, Masahiro Kikuya, Abraham A. Kroon, Lenore J. Launer, Rajiv Mahajan, Emer R. McGrath, Simon P. Mooijaart, Eric P. Moll Van Charante, Michiaki Nagai, Toshiharu Ninomiya, Tomoyuki Ohara, Takayoshi Ohkubo, Emi Oishi, Ruth Peters, Edo Richard, Michihiro Satoh, Sudha Seshadri, David J. Stott, Willem A. Van Gool, Tessa Van Middelaar, Stella Trompet, Kristy Giles, Phoebe Drioli-Phillips, Umama Aaimir, Frank Connolly, Christophe Tzourio, The association between blood pressure variability (BPV) with dementia and cognitive function A systematic review and meta-analysis protocol 11 Medical and Health Sciences 1117 Public Health and Health Services, Systematic Reviews, 10.1186/s13643-018-0811-9, 7, 1, 2018.10, [URL], Background: A body of empirical work demonstrates that wide fluctuations in a person's blood pressure across consecutive measures, known as blood pressure variability (BPV), hold prognostic value to predict stroke and transient ischemic attack. However, the magnitude of association between BPV and other neurological outcomes remains less clear. This systematic review aims to pool together data regarding BPV with respect to incident dementia, cognitive impairment, and cognitive function. Methods: Electronic databases (MEDLINE, EMBASE, and SCOPUS) will be searched for the key words blood pressure variability and outcomes of dementia, cognitive impairment, and cognitive function. Authors and reference lists of included studies will also be contacted to identify additional published and unpublished studies. Eligibility criteria are as follows: population - adult humans (over 18 years but with no upper age limit) without dementia at baseline, with or without elevated blood pressure, or from hypertensive populations (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or use of antihypertensive drug for hypertension) and from primary care, community cohort, electronic database registry, or randomized controlled trial (RCT); exposure - any metric of BPV (systolic, diastolic or both) over any duration; comparison - persons without dementia who do not have elevated BPV; and outcome - dementia, cognitive impairment, cognitive function at follow-up from standardized neurological assessment, or cognitive testing. Article screening will be undertaken by two independent reviewers with disagreements resolved through discussion. Data extraction will include original data specified as hazard ratios, odds ratios, correlations, regression coefficients, and original cell data if available. Risk of bias assessment will be undertaken by two independent reviewers. Meta-analytic methods will be used to synthesize the data collected relating to the neurological outcomes with Comprehensive Meta-Analysis Version 2.0 (Biostat Inc., Engelwood, NJ). Discussion: This systematic review aims to clarify whether BPV is associated with elevated risk for dementia, cognitive impairment, and cognitive function. An evaluation of the etiological links between BPV with incident dementia might inform evidence-based clinical practice and policy concerning blood pressure measurement and hypertension management. The review will identify sources of heterogeneity and may inform decisions on whether it is feasible and desirable to proceed with an individual participant data meta-analysis.. |
| 90. | Ohara T, Honda T, Hata J, Yoshida D, Mukai N, Hirakawa Y, Shibata M, Kishimoto H, Kitazono T, Kanba S, Ninomiya T, Association Between Daily Sleep Duration and Risk of Dementia and Mortality in a Japanese Community., Journal of the American Geriatrics Society, 10.1111/jgs.15446, 66, 10, 1911-1918, 2018.10. |
| 91. | Tomoyuki Ohara, Toshiharu Ninomiya, Reply to “Long sleep duration An epiphenomenon or a risk for dementia?”, Journal of the American Geriatrics Society, 10.1111/jgs.15558, 66, 11, 2225-2226, 2018.11, [URL]. |
| 92. | Ohara T, Ninomiya T, Reply to "Long sleep duration: An epiphenomenon or a risk for dementia?", Journal of the American Geriatrics Society, 10.1111/jgs.15558, 66, 11, 2225-2226, 2018.11. |
| 93. | Hatabe Y, Shibata M, Ohara T, Oishi E, Yoshida D, Honda T, Hata J, Kanba S, Kitazono T, Ninomiya T, Decline in handgrip strength from midlife to late-life is associated with dementia in a Japanese community: the Hisayama Study., Journal of epidemiology, 10.2188/jea.JE20180137, 30, 1, 15-23, 2018.12. |
| 94. | Tomoyuki Ohara, Jun Hata, Masashi Tanaka, Takanori Honda, Hajime Yamakage, Daigo Yoshida, Takayuki Inoue, Yoichiro Hirakawa, Toru Kusakabe, Mao Shibata, Tadashi Teraoka, Takanari Kitazono, Shigenobu Kanba, Noriko Satoh-Asahara, Toshiharu Ninomiya, Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia The Hisayama Study, Annals of Neurology, 10.1002/ana.25385, 85, 1, 47-58, 2019.01, [URL], Objective: To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia. Methods: A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002–2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia. Results: During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend 0.11). Interpretation: The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47–58.. |
| 95. | Ohara T, Hata J, Tanaka M, Honda T, Yamakage H, Yoshida D, Inoue T, Hirakawa Y, Kusakabe T, Shibata M, Teraoka T, Kitazono T, Kanba S, Satoh-Asahara N, Ninomiya T, Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study., Annals of neurology, 10.1002/ana.25385, 85, 1, 47-58, 2019.01. |
| 96. | Akihiro Tanaka, Jun Hata, Naoki Akamatsu, Naoko Mukai, Yoichiro Hirakawa, Daigo Yoshida, Hiro Kishimoto, Tomoyuki Ohara, Toshiki Mizuno, Sadatoshi Tsuji, Takanari Kitazono, Toshiharu Ninomiya, Prevalence of adult epilepsy in a general Japanese population The Hisayama study, Epilepsia Open, 10.1002/epi4.12295, 4, 1, 182-186, 2019.03, [URL], The aim of the present study was to examine the prevalence and causes of adult epilepsy in a general Japanese population. We examined a total of 3333 Japanese residents in the town of Hisayama aged ≥40 years in 2012-2013. The examination was performed mainly at the municipal center for health promotion, but some subjects were examined in their homes, hospitals, or nursing homes. Twenty-three subjects had a diagnosis of epilepsy. The prevalence (95% confidence interval [CI]) of epilepsy per 1000 was 6.9 (4.1-9.7) in total, 4.9 (1.3-8.5) in men, and 8.4 (4.3-12.5) in women (P = 0.23 between sexes). The prevalence of epilepsy was significantly higher in the elderly (aged ≥65 years; 10.3 per 1000 [95% CI 5.4-15.1]) than in the middle-aged (aged 40-64 years; 3.6 per 1000 [95% CI 0.7-6.4]; P = 0.02). The major cause of epilepsy was cerebrovascular diseases (n = 11; 48% of the epilepsy patients). More than half of the epilepsy patients experienced the first episode of seizure in older age (≥65 years; n = 13; 57%). The findings of this study suggest the clinical importance of the prevention of cerebrovascular diseases to reduce the burden of epilepsy in the future.. |
| 97. | Tanaka A, Hata J, Akamatsu N, Mukai N, Hirakawa Y, Yoshida D, Kishimoto H, Ohara T, Mizuno T, Tsuji S, Kitazono T, Ninomiya T, Prevalence of adult epilepsy in a general Japanese population: The Hisayama study., Epilepsia open, 10.1002/epi4.12295, 4, 1, 182-186, 2019.03. |
| 98. | 本田 貴紀, 吉田 大悟, 岸本 裕歩, 小原 知之, 平林 直樹, 古田 芳彦, 二宮 利治, 地域住民における中年期から高齢期にかけての長期の運動歴と認知機能低下に関する研究 : 前向きコホート研究, 34, 40-45, 2019.04. |
| 99. | Takanori Honda, Hiro Kishimoto, Naoko Mukai, Jun Hata, Daigo Yoshida, Yoichiro Hirakawa, Mao Shibata, Tomoyuki Ohara, Shuzo Kumagai, Toshiharu Ninomiya, Objectively measured sedentary time and diabetes mellitus in a general Japanese population The Hisayama Study, Journal of Diabetes Investigation, 10.1111/jdi.12968, 10, 3, 809-816, 2019.05, [URL], Aims/Introduction: The present study aimed to examine cross-sectional associations between objectively measured sedentary time and the prevalence of diabetes mellitus in a general Japanese population, and to elucidate possible mediating roles of diet, obesity and insulin resistance in this relationship. Materials and Methods: A total of 1,758 community-dwelling individuals aged 40–79 years wore an accelerometer for ≥7 days and underwent a comprehensive health examination in 2012. Diabetes mellitus was diagnosed by a 75-g oral glucose tolerance test. The associations of sedentary time with the presence of diabetes mellitus and the levels of the homeostasis model assessment of insulin resistance were estimated by logistic and linear regression models. Results: After adjustment for demographic and lifestyle factors including moderate-to-vigorous physical activity, participants who spent ≥10 h in sedentary time had a significantly higher odds ratio of the presence of diabetes than those who spent |
| 100. | Hata J, Ohara T, Katakura Y, Shimizu K, Yamashita S, Yoshida D, Honda T, Hirakawa Y, Shibata M, Sakata S, Kitazono T, Kuhara S, Ninomiya T, Association Between Serum β-alanine and Risk of Dementia: the Hisayama Study., American journal of epidemiology, 10.1093/aje/kwz116, 2019.05. |
| 101. | Honda T, Kishimoto H, Mukai N, Hata J, Yoshida D, Hirakawa Y, Shibata M, Ohara T, Kumagai S, Ninomiya T, Objectively measured sedentary time and diabetes mellitus in a general Japanese population: The Hisayama Study., Journal of diabetes investigation, 10.1111/jdi.12968, 10, 3, 809-816, 2019.05. |
| 102. | Daigo Yoshida, Tomoyuki Ohara, Jun Hata, Mao Shibata, Yoichiro Hirakawa, Takanori Honda, Kazuhiro Uchida, Satoshi Takasugi, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya, Dairy consumption and risk of functional disability in an elderly Japanese population The Hisayama Study, American Journal of Clinical Nutrition, 10.1093/ajcn/nqz040, 109, 6, 1664-1671, 2019.06, [URL], Background: Little is known about the association between dairy intake and risk of functional disability in the elderly. Objectives: We examined the influence of dairy intake on the development of declining functional capacity and activities of daily living (ADL) in a prospective cohort study of an elderly population. Methods: A total of 859 community-dwelling Japanese residents, aged ?65 y without functional disability, were followed up for 7 y. Functional capacity impairment was defined as a TokyoMetropolitan Institute of Gerontology Index of Competence score of ≥12, and ADL disability was defined as a Barthel Index score of ≥95. Dairy intake was evaluated using a 150-item semiquantitative food frequency questionnaire, grouped into quartiles. The RR of dairy intake on incident functional disabilitywas computed using a Poisson regression model. Results: The multivariable-Adjusted RR of impaired functional capacity decreased significantly with increasing dairy intake levels (RR [95% CI]: quartile 1, 1.00 [reference]; quartile 2, 0.85 [0.71, 1.02]; quartile 3, 0.81 [0.68, 0.98]; and quartile 4, 0.74 [0.61, 0.90]; P-Trend = 0.001). Regarding the three subscales of functional capacity, the inverse association between dairy intake and risk for impairment of intellectual activity and social role remained significant (P-Trend = 0.0009 and 0.02, respectively), but such an association was not observed for instrumental ADL. The multivariable-Adjusted risk of ADL disability also decreased weakly but significantly with elevating dairy intake (P-Trend=0.04). A similar association was seen for severity of functional disability (P-Trend = 0.002). However, the magnitude of these associations was attenuated after further adjustment for protein intake. Conclusion: Our findings suggest that higher dairy intake is associated with a lower risk of functional disability and its progression in the elderly, probably via an increase in protein intake.. |
| 103. | Yoshida D, Ohara T, Hata J, Shibata M, Hirakawa Y, Honda T, Uchida K, Takasugi S, Kitazono T, Kiyohara Y, Ninomiya T, Dairy consumption and risk of functional disability in an elderly Japanese population: the Hisayama Study., The American journal of clinical nutrition, 10.1093/ajcn/nqz040, 109, 6, 1664-1671, 2019.06. |
| 104. | Naoko Mukai, Jun Hata, Yoichiro Hirakawa, Tomoyuki Ohara, Daigo Yoshida, Udai Nakamura, Takanari Kitazono, Toshiharu Ninomiya, Trends in the prevalence of type 2 diabetes and prediabetes in a Japanese community, 1988–2012 the Hisayama Study, Diabetology International, 10.1007/s13340-018-0380-0, 10, 3, 198-205, 2019.07, [URL], Objective: We estimated secular trends in the prevalence of type 2 diabetes (T2DM) and prediabetes, and examined potential explanatory factors for these trends in a Japanese community. Methods: 4 cross-sectional examinations were conducted among subjects aged 40–79 years in 1988 (n = 2,490), 2002 (n = 2,856), 2007 (n = 2,761), and 2012 (n = 2,644). Glucose tolerance status was defined by a 75g oral glucose tolerance test. Results: The age-standardized prevalence of T2DM increased significantly in both sexes from 1988 to 2002, and thereafter it remained stable in men, and decreased nonsignificantly in women from 2002 to 2012. The age-standardized prevalence of prediabetes in men increased significantly between 1988 and 2002, but then decreased significantly. A similar trend was observed in women. The age-specific prevalence of T2DM increased greatly in men aged 60–79 years and women aged 70–79 years from 1988 to 2002, and then plateaued at a high level, while a significant decreasing trend was observed in women aged 40–49 years. The mean values of body mass index (BMI) increased steeply in these elderly subjects from 1988 to 2002, and remained at a high level, whereas those in middle-aged women decreased appreciably over the study period. Conclusions: Our findings suggest that in Japanese, there was no further increase in the prevalence of T2DM or prediabetes in either men or women in the 2000s. Secular change in the BMI level was likely to contribute to trends in the prevalence of T2DM, and thus the management of obesity may be important to reduce the prevalence of T2DM.. |
| 105. | Mukai N, Hata J, Hirakawa Y, Ohara T, Yoshida D, Nakamura U, Kitazono T, Ninomiya T, Trends in the prevalence of type 2 diabetes and prediabetes in a Japanese community, 1988-2012: the Hisayama Study., Diabetology international, 10.1007/s13340-018-0380-0, 10, 3, 198-205, 2019.07. |
| 106. | Jun Hata, Tomoyuki Ohara, Yoshinori Katakura, Kuniyoshi Shimizu, Shuntaro Yamashita, Daigo Yoshida, Takanori Honda, Yoichiro Hirakawa, Mao Shibata, Satoko Sakata, Takanari Kitazono, Satoru Kuhara, Toshiharu Ninomiya, Association between Serum β-Alanine and Risk of Dementia, American journal of epidemiology, 10.1093/aje/kwz116, 188, 9, 1637-1645, 2019.09, [URL], We examined the association between serum concentrations of β-alanine, a metabolite of carnosine and anserine, and the risk of dementia in a general population of elderly Japanese persons. In 2007, 1,475 residents of Hisayama, Japan, aged 60-79 years and without dementia were divided into 4 groups according to quartiles of serum β-alanine concentrations (quartile 1, lowest; quartile 4, highest) and followed for a median of 5.3 years. During follow-up, 117 subjects developed all-cause dementia (Alzheimer in 77 cases and vascular dementia in 31). The risk of all-cause dementia decreased with increasing serum β-alanine levels after adjustment for potential confounding factors (quartile 2, hazard ratio (HR) = 0.73 (95% confidence interval (CI): 0.45, 1.18); quartile 3, HR = 0.50 (95% CI: 0.28, 0.89); quartile 4, HR = 0.50 (95% CI: 0.27, 0.92); P = 0.01 for trend). A similar inverse association was observed for Alzheimer disease (quartile 2, HR = 0.78 (95% CI: 0.44, 1.38); quartile 3, HR = 0.53 (95% CI: 0.26, 1.06); quartile 4, HR = 0.53 (95% CI: 0.25, 1.10); P = 0.04 for trend) but not for vascular dementia. We found that higher serum β-alanine levels were significantly associated with lower risks of all-cause dementia and Alzheimer disease. Because serum β-alanine levels reflect intakes of carnosine/anserine, higher intakes of carnosine/anserine might be beneficial for the prevention of dementia.. |
| 107. | Takuya Nagata, Tomoyuki Ohara, Jun Hata, Satoko Sakata, Yoshihiko Furuta, Daigo Yoshida, Takanori Honda, Yoichiro Hirakawa, Tomomi Ide, Shigenobu Kanba, Takanari Kitazono, Hiroyuki Tsutsui, Toshiharu Ninomiya, NT-proBNP and Risk of Dementia in a General Japanese Elderly Population The Hisayama Study, Journal of the American Heart Association, 10.1161/JAHA.118.011652, 8, 17, e011652, 2019.09, [URL], Background Epidemiological evidence implies a link between heart disease and dementia. However, few prospective studies have assessed the association between serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels and dementia. Methods and Results A total of 1635 community-dwelling Japanese elderly aged ≥60 years without dementia (57% women, mean age±SD 70.8±7.7 years) were followed up for 10 years. Serum NT-proBNP levels were divided into 4 categories (≤54, 55-124, 125-299, and ≥300 pg/mL). The hazard ratios were estimated using a Cox proportional hazards model. During the follow-up period, 377 subjects developed all-cause dementia, 247 Alzheimer disease, and 102 vascular dementia. The age- and sex-adjusted incidence of all-cause dementia was 31.5 per 1000 person-years and increased significantly with higher serum NT-proBNP levels, being 16.4, 32.0, 35.7, and 45.5, respectively (P for trend |
| 108. | Nagata T, Ohara T, Hata J, Sakata S, Furuta Y, Yoshida D, Honda T, Hirakawa Y, Ide T, Kanba S, Kitazono T, Tsutsui H, Ninomiya T, NT-proBNP and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study., Journal of the American Heart Association, 10.1161/JAHA.118.011652, 8, 17, e011652, 2019.09. |
| 109. | Honda T, Ohara T, Shinohara M, Hata J, Toh R, Yoshida D, Shibata M, Ishida T, Hirakawa Y, Irino Y, Sakata S, Uchida K, Kitazono T, Kanba S, Hirata KI, Ninomiya T, Serum elaidic acid concentration and risk of dementia: The Hisayama study., Neurology, 10.1212/WNL.0000000000008464, 93, 22, e2053-e2064, 2019.10. |
| 110. | Takanori Honda, Tomoyuki Ohara, Masakazu Shinohara, Jun Hata, Ryuji Toh, Daigo Yoshida, Mao Shibata, Tatsuro Ishida, Yoichiro Hirakawa, Yasuhiro Irino, Satoko Sakata, Kazuhiro Uchida, Takanari Kitazono, Shigenobu Kanba, Ken Ichi Hirata, Toshiharu Ninomiya, Serum elaidic acid concentration and risk of dementia The Hisayama Study, Neurology, 10.1212/WNL.0000000000008464, 93, 22, E2053-E2064, 2019.11, [URL], ObjectiveThe associations between trans fatty acids and dementia have been unclear. We investigated the prospective association between serum elaidic acid (trans 18:1 n-9) levels, as an objective biomarker for industrial trans fat, and incident dementia and its subtypes.MethodsIn total, 1,628 Japanese community residents aged 60 and older without dementia were followed prospectively from when they underwent a screening examination in 2002-2003 to November 2012 (median 10.3 years, interquartile range 7.2-10.4 years). Serum elaidic acid levels were measured using gas chromatography/mass spectrometry and divided into quartiles. The Cox proportional hazards model was used to estimate the hazard ratios for all-cause dementia, Alzheimer disease (AD), and vascular dementia by serum elaidic acid levels.ResultsDuring the follow-up, 377 participants developed some type of dementia (247 AD, 102 vascular dementia). Higher serum elaidic acid levels were significantly associated with greater risk of developing all-cause dementia (p for trend = 0.003) and AD (p for trend = 0.02) after adjustment for traditional risk factors. These associations remained significant after adjustment for dietary factors, including total energy intake and intakes of saturated and polyunsaturated fatty acids (both p for trend |
| 111. | Hideomi Hamasaki, Hiroyuki Honda, Satoshi O. Suzuki, Masahiro Shijo, Tomoyuki Ohara, Yozo Hatabe, Tsuyoshi Okamoto, Toshiharu Ninomiya, Toru Iwaki, Tauopathy in basal ganglia involvement is exacerbated in a subset of patients with Alzheimer's disease The Hisayama study, Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 10.1016/j.dadm.2019.04.008, 11, 415-423, 2019.12, [URL], Introduction: We have conducted the pathological cohort study of autopsied cases of Hisayama residents to reveal a recent trend of dementia-related pathology. We noticed a trend of putaminal involvement of Alzheimer's disease (AD) with parkinsonism. Then, we investigated the accurate prevalence of neurological diseases with putaminal AD pathology in the general population. Methods: We examined a series of 291 autopsies in the Hisayama study and performed image analysis of immunohistochemistry for microtubule-associated protein tau (MAPT) and amyloid β. Results: Approximately 65.6% and 36.1% of cases showed putaminal MAPT and amyloid deposits, respectively. Diffuse deposits of them were mainly found in the AD cases. Putaminal MAPT was highly associated with AD-related pathological criteria. Four of 22 cases with severe putaminal MAPT deposition were documented as having developed parkinsonism. Discussion: Severe MAPT accumulation in the basal ganglia was closely related to the development of AD pathology and could occur most frequently in AD cases without comorbidities.. |
| 112. | Hamasaki H, Honda H, Suzuki SO, Shijo M, Ohara T, Hatabe Y, Okamoto T, Ninomiya T, Iwaki T, Tauopathy in basal ganglia involvement is exacerbated in a subset of patients with Alzheimer's disease: The Hisayama study., Alzheimer's & dementia (Amsterdam, Netherlands), 10.1016/j.dadm.2019.04.008, 11, 415-423, 2019.12. |
| 113. | , Phillip J. Tully, Yuichiro Yano, Lenore J. Launer, Kazuomi Kario, Michiaki Nagai, Simon P. Mooijaart, Jurgen A.H.R. Claassen, Simona Lattanzi, Andrew D. Vincent, Christophe Tzourio, Kaarin J. Anstey, Nigel Beckett, Alexa S. Beiser, Jonathan Birns, Adam M. Brickman, Nicholas R. Burns, Mahir Cengiz, Suzanne Cosh, Rianne A.A. de Heus, Peter W. de Leeuw, Diana Dorstyn, Merrill F. Elias, J. Wouter Jukema, Masahiro Kikuya, Abraham A. Kroon, Rajiv Mahajan, Emer R. McGrath, Eric P. Moll van Charante, Toshiharu Ninomiya, Tomoyuki Ohara, Takayoshi Ohkubo, Emi Oishi, Ruth Peters, Edo Richard, Michihiro Satoh, Joseph Selvayanagam, Sudha Seshadri, David J. Stott, Stella Trompet, Willem A. van Gool, Tessa van Middelaar, Deborah A. Turnbull, Association Between Blood Pressure Variability and Cerebral Small-Vessel Disease A Systematic Review and Meta-Analysis, Journal of the American Heart Association, 10.1161/JAHA.119.013841, 9, 1, 2020.01, [URL], Background: Research links blood pressure variability (BPV) with stroke; however, the association with cerebral small-vessel disease (CSVD) remains unclear. As BPV and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding cerebrovascular morphological characteristics. Methods and Results: A systematic review was performed from inception until March 3, 2019. Eligibility criteria included population, adults without stroke (2=85%) independent of mean systolic pressure. Likewise, higher diastolic BPV was associated with higher odds for CSVD (OR, 1.30; 95% CI, 1.14–1.48; I2=53%) independent of mean diastolic pressure. There was no evidence of a pairwise interaction between systolic/diastolic and BPV/mean ORs (P=0.47), nor a difference between BPV versus mean pressure ORs (P=0.58). Fifty-four standardized mean differences were pooled and provided similar results for pairwise interaction (P=0.38) and difference between standardized mean differences (P=0.70). Conclusions: On the basis of the available studies, BPV was associated with CSVD independent of mean blood pressure. However, more high-quality longitudinal data are required to elucidate whether BPV contributes unique variance to CSVD morphological characteristics.. |
| 114. | Yozo Hatabe, Mao Shibata, Tomoyuki Ohara, Emi Oishi, Daigo Yoshida, Takanori Honda, Jun Hata, Shigenobu Kanba, Takanari Kitazono, Toshiharu Ninomiya, Decline in handgrip strength from midlife to late-life is associated with dementia in a Japanese community The Hisayama study, Journal of epidemiology, 10.2188/jea.JE20180137, 30, 1, 15-23, 2020.01, [URL], Background: The association between decline in handgrip strength from midlife to late life and dementia is unclear. Methods: Japanese community-dwellers without dementia aged 60 to 79 years (ie, individuals in late life; mean age, 68 years) were followed for 24 years (1988–2012) (n = 1,055); 835 of them had participated in a health examination in 1973–1974 (mean age, 53 years), and these earlier data were used for the midlife analysis. Using a Cox proportional hazards model, we estimated the risk conferred by a decline in handgrip strength over a 15-year period (1973–74 to 1988) from midlife to late life on the development of total dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) over the late-life follow-up period from 1988 to 2012. Results: During the follow-up, 368 subjects experienced total dementia. The age-and sex-adjusted incidence of total dementia increased significantly with greater decline in handgrip strength (increased or unchanged handgrip strength [≥+0%] 25.1, mildly decreased [−14 to −1%] 28.4, and severely decreased [≤−15%] 38.9 per 1,000 person-years). A greater decline in handgrip strength was significantly associated with higher risk of total dementia after adjusting for potential confounding factors; subjects with severely decreased handgrip strength had 1.51-fold (95% confidence interval, 1.14–1.99, P |
| 115. | Tomoyuki Ohara, Yoshihiko Furuta, Naoki Hirabayashi, Jun Hata, Yoichiro Hirakawa, Takanori Honda, Daigo Yoshida, Mao Shibata, Takanari Kitazono, Toshiharu Ninomiya, Elevated serum glycated albumin and glycated albumin : hemoglobin A1c ratio were associated with hippocampal atrophy in a general elderly population of Japanese: the Hisayama Study, Journal of Diabetes Investigation, 10.1111/jdi.13220, 2020.01, [URL], Aims/Introduction: To investigate the association of alternative glycemic measures – namely, serum glycated albumin (GA), hemoglobin A1c and the GA : HbA1cratio – with global brain and hippocampal atrophy in a general elderly Japanese population. Materials and Methods: A total of 1,278 Japanese individuals aged ≥65 years in a community participated in brain magnetic resonance imaging scanning and screening examination of health status in 2012. We measured total brain volume (TBV), hippocampal volume (HV) and intracranial volume (ICV) using the data from the magnetic resonance imaging examination. The association of each glycemic measure with the ratios of TBV : ICV (an indicator of global brain atrophy) and HV : ICV (an indicator of hippocampal atrophy) was examined by analysis of covariance. Results: The mean values of the TBV : ICV and HV : ICV ratios decreased significantly with elevating serum GA levels and GA : HbA1c ratio levels (all P for trend 1c levels, after adjusting for age, sex, low education, systolic blood pressure, antihypertensive medication, diabetes mellitus, serum total cholesterol, electrocardiogram abnormalities, body mass index, smoking habits, alcohol drinking habits and regular exercise. These significant associations were still observed in the sensitivity analysis after excluding individuals with mild cognitive impairment and dementia. In addition, increased serum GA levels and the GA : HbA1c ratio levels, but not HbA1c, were closely associated with lower mean values of the TBV : ICV and HV : ICV ratios, irrespective of the presence or absence of diabetes mellitus. Conclusions: The present study suggests that higher serum GA and higher GA : HbA1c ratio are significantly associated with global brain and hippocampal atrophy.. |
| 116. | Tomoyuki Ohara, Yoshihiko Furuta, Naoki Hirabayashi, Jun Hata, Yoichiro Hirakawa, Takanori Honda, Daigo Yoshida, Mao Shibata, Takanari Kitazono, Toshiharu Ninomiya, Elevated serum glycated albumin and glycated albumin : hemoglobin A1c ratio were associated with hippocampal atrophy in a general elderly population of Japanese: The Hisayama Study., Journal of diabetes investigation, 10.1111/jdi.13220, 11, 4, 971-979, 2020.01, AIMS/INTRODUCTION: To investigate the association of alternative glycemic measures - namely, serum glycated albumin (GA), hemoglobin A1c (HbA1c ) and the GA : HbA1c ratio - with global brain and hippocampal atrophy in a general elderly Japanese population. MATERIALS AND METHODS: A total of 1,278 Japanese individuals aged ≥65 years in a community participated in brain magnetic resonance imaging scanning and screening examination of health status in 2012. We measured total brain volume (TBV), hippocampal volume (HV) and intracranial volume (ICV) using the data from the magnetic resonance imaging examination. The association of each glycemic measure with the ratios of TBV : ICV (an indicator of global brain atrophy) and HV : ICV (an indicator of hippocampal atrophy) was examined by analysis of covariance. RESULTS: The mean values of the TBV : ICV and HV : ICV ratios decreased significantly with elevating serum GA levels and GA : HbA1c ratio levels (all P for trend |
| 117. | Sanmei Chen, Takanori Honda, Tomoyuki Ohara, Jun Hata, Yoichiro Hirakawa, Daigo Yoshida, Mao Shibata, Satoko Sakata, Emi Oishi, Yoshihiko Furuta, Takanari Kitazono, Toshiharu Ninomiya, Serum homocysteine and risk of dementia in Japan., Journal of neurology, neurosurgery, and psychiatry, 10.1136/jnnp-2019-322366, 2020.03, OBJECTIVE: To examine the association between serum total homocysteine levels (tHcy) and dementia risk. METHODS: A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia. RESULTS: During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07). CONCLUSION: High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.. |
| 118. | Crystal Man Ying Lee, Mark Woodward, G. David Batty, Alexa S. Beiser, Steven Bell, Claudine Berr, Espen Bjertness, John Chalmers, Robert Clarke, Jean Francois Dartigues, Kendra Davis-Plourde, Stéphanie Debette, Emanuele Di Angelantonio, Catherine Feart, Ruth Frikke-Schmidt, John Gregson, Mary N. Haan, Linda B. Hassing, Kathleen M. Hayden, Marieke P. Hoevenaar-Blom, Jaakko Kaprio, Mika Kivimaki, Georgios Lappas, Eric B. Larson, Erin S. LeBlanc, Anne Lee, Li Yung Lui, Eric P. Moll van Charante, Toshiharu Ninomiya, Liv Tybjærg Nordestgaard, Tomoyuki Ohara, Toshiaki Ohkuma, Teemu Palviainen, Karine Peres, Ruth Peters, Nawab Qizilbash, Edo Richard, Annika Rosengren, Sudha Seshadri, Martin Shipley, Archana Singh-Manoux, Bjorn Heine Strand, Willem A. van Gool, Eero Vuoksimaa, Kristine Yaffe, Rachel R. Huxley, Association of anthropometry and weight change with risk of dementia and its major subtypes A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia, Obesity Reviews, 10.1111/obr.12989, 21, 4, 2020.04, [URL], Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index–defined lower-normal weight (18.5-22.4 kg/m2), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.. |
| 119. | Crystal ManYing Lee, Mark Woodward, G David Batty, Alexa S Beiser, Steven Bell, Claudine Berr, Espen Bjertness, John Chalmers, Robert Clarke, Jean-Francois Dartigues, Kendra Davis-Plourde, Stéphanie Debette, Emanuele Di Angelantonio, Catherine Feart, Ruth Frikke-Schmidt, John Gregson, Mary N Haan, Linda B Hassing, Kathleen M Hayden, Marieke P Hoevenaar-Blom, Jaakko Kaprio, Mika Kivimaki, Georgios Lappas, Eric B Larson, Erin S LeBlanc, Anne Lee, Li-Yung Lui, Eric P Moll van Charante, Toshiharu Ninomiya, Liv Tybjaerg Nordestgaard, Tomoyuki Ohara, Toshiaki Ohkuma, Teemu Palviainen, Karine Peres, Ruth Peters, Nawab Qizilbash, Edo Richard, Annika Rosengren, Sudha Seshadri, Martin Shipley, Archana Singh-Manoux, Bjorn Heine Strand, Willem A van Gool, Eero Vuoksimaa, Kristine Yaffe, Rachel R Huxley, Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia., Obesity reviews : an official journal of the International Association for the Study of Obesity, 10.1111/obr.12989, 21, 4, e12989, 2020.04, Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.. |
| 120. | Sanmei Chen, Takanori Honda, Tomoyuki Ohara, Jun Hata, Yoichiro Hirakawa, Daigo Yoshida, Mao Shibata, Satoko Sakata, Emi Oishi, Yoshihiko Furuta, Takanari Kitazono, Toshiharu Ninomiya, Serum homocysteine and risk of dementia in Japan, Journal of Neurology, Neurosurgery and Psychiatry, 10.1136/jnnp-2019-322366, 91, 5, 540-546, 2020.05, [URL], Objective To examine the association between serum total homocysteine levels (tHcy) and dementia risk. Methods A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia. Results During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 μmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 μmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 μmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07). Conclusion High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.. |
| 121. | Keisuke Yamasaki, Jun Hata, Yoshihiko Furuta, Naoki Hirabayashi, Tomoyuki Ohara, Daigo Yoshida, Yoichiro Hirakawa, Toshiaki Nakano, Takanari Kitazono, Toshiharu Ninomiya, Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese - The Hisayama Study., Circulation journal : official journal of the Japanese Circulation Society, 10.1253/circj.CJ-19-1069, 84, 6, 935-942, 2020.05, BACKGROUND: Both chronic kidney disease and brain white matter hyperintensities (WMH) are known to be risk factors of dementia and mortality.Methods and Results:In 2012, 1,214 community-dwelling Japanese subjects aged ≥65 years underwent brain magnetic resonance imaging (MRI) scans and a comprehensive health examination. This study investigated associations of the urinary albumin : creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with the WMH volume to intracranial volume (WMHV : ICV) ratio, and the association of the combination of UACR and the WMHV : ICV ratio with cognitive decline and mortality risk. The geometric mean of the WMHV : ICV ratio was 0.223% in the entire study population, and increased significantly with higher UACR levels after adjusting for potential confounding factors (0.213% for normoalbuminuria, 0.248% for microalbuminuria, and 0.332% for macroalbuminuria; Ptrend=0.01). In contrast, there was no clear association between eGFR and the WMHV : ICV ratio. Compared with subjects with normoalbuminuria and a smaller WMHV : ICV ratio ( |
| 122. | Daigo Yoshida, Tomoyuki Ohara, Jun Hata, Mao Shibata, Yoichiro Hirakawa, Takanori Honda, Yoshihiko Furuta, Emi Oishi, Satoko Sakata, Shigenobu Kanba, Takanari Kitazono, Toshiharu Ninomiya, Lifetime cumulative incidence of dementia in a community-dwelling elderly population in Japan., Neurology, 10.1212/WNL.0000000000009917, 95, 5, e508-e518, 2020.08, OBJECTIVE: To estimate the lifetime cumulative incidence of dementia and its subtypes from a community-dwelling elderly population in Japan. METHODS: A total of 1,193 community-dwelling Japanese individuals without dementia, aged 60 years or older, were followed up prospectively for 17 years. The cumulative incidence of dementia was estimated based on a death- and dementia-free survival function and the hazard functions of dementia at each year, which were computed by using a Weibull proportional hazards model. The lifetime risk of dementia was defined as the cumulative incidence of dementia at the point in time when the survival probability of the population was estimated to be less than 0.5%. RESULTS: During the follow-up, 350 participants experienced some type of dementia; among them, 191 participants developed Alzheimer disease (AD) and 117 developed vascular dementia (VaD). The lifetime risk of dementia was 55% (95% confidence interval, 49%-60%). Women had an approximately 1.5 times greater lifetime risk of dementia than men (65% [57%-72%] vs 41% [33%-49%]). The lifetime risks of developing AD and VaD were 42% (35%-50%) and 16% (12%-21%) in women vs 20% (7%-34%) and 18% (13%-23%) in men, respectively. CONCLUSION: Lifetime risk of all dementia for Japanese elderly was substantial at approximately 50% or higher. This study suggests that the lifetime burden attributable to dementia in contemporary Japanese communities is immense.. |
| 123. | Akane Mihara, Tomoyuki Ohara, Jun Hata, Takanori Honda, Sanmei Chen, Satoko Sakata, Emi Oishi, Yoichiro Hirakawa, Tomohiro Nakao, Takanari Kitazono, Toshiharu Ninomiya, Association between serum glycated albumin and risk of cardiovascular disease in a Japanese community: The Hisayama Study., Atherosclerosis, 10.1016/j.atherosclerosis.2020.08.016, 311, 52-59, 2020.10, BACKGROUND AND AIMS: We aimed to investigate the association of serum glycated albumin (GA) levels with the risk of cardiovascular disease (CVD) and its subtypes, including coronary heart disease (CHD) and stroke, in a general Japanese population. METHODS: A total of 2965 Japanese community-dwellers aged ≥40 years were followed prospectively for a median of 10.2 years (2002-2012). Serum GA was measured by the enzymatic method and divided into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum GA levels on CVD risk. RESULTS: During the follow-up, 213 subjects developed CVD; 95 had CHD, and 133 had stroke. The cumulative incidence of CVD, CHD, and stroke increased significantly with increasing serum GA levels (all p for trend |
| 124. | Emer R McGrath, Jayandra J Himali, Daniel Levy, Sarah C Conner, Charles DeCarli, Matthew P Pase, Toshiharu Ninomiya, Tomoyuki Ohara, Paul Courchesne, Claudia L Satizabal, Ramachandran S Vasan, Alexa S Beiser, Sudha Seshadri, Growth Differentiation Factor 15 and NT-proBNP as Blood-Based Markers of Vascular Brain Injury and Dementia., Journal of the American Heart Association, 10.1161/JAHA.119.014659, 9, 19, e014659, 2020.10, Background GDF15 (growth differentiation factor 15) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may offer promise as biomarkers for cognitive outcomes, including dementia. We determined the association of these biomarkers with cognitive outcomes in a community-based cohort. Methods and Results Plasma GDF15 (n=1603) and NT-proBNP levels (n=1590) (53% women; mean age, 68.7 years) were measured in dementia-free Framingham Offspring cohort participants at examination 7 (1998-2001). Participants were followed up for incident dementia. Secondary outcomes included Alzheimer disease dementia, magnetic resonance imaging structural brain measures, and neurocognitive performance. During a median 11.8-year follow-up, 131 participants developed dementia. On multivariable Cox proportional-hazards analysis, higher circulating GDF15 was associated with an increased risk of incident all-cause and Alzheimer disease dementia (hazard ratio [HR] per SD increment in natural log-transformed biomarker value, 1.54 [95% CI, 1.22-1.95] and 1.37 [95% CI, 1.03-1.81], respectively), whereas higher plasma NT-proBNP was also associated with an increased risk of all-cause dementia (HR, 1.32; 95% CI, 1.05-1.65). Elevated GDF15 was associated with lower total brain and hippocampal volumes, greater white matter hyperintensity volume, and poorer cognitive performance. Elevated NT-proBNP was associated with greater white matter hyperintensity volume and poorer cognitive performance. Addition of both biomarkers to a conventional risk factor model improved dementia risk classification (net reclassification improvement index, 0.25; 95% CI, 0.05-0.45). Conclusions Elevated plasma GDF15 and NT-proBNP were associated with vascular brain injury on magnetic resonance imaging, poorer neurocognitive performance, and increased risk of incident dementia in individuals aged >60 years. Both biomarkers improved dementia risk classification beyond that of traditional clinical risk factors, indicating their potential value in predicting incident dementia.. |
| 125. | Toshiharu Ninomiya, Shigeyuki Nakaji, Tetsuya Maeda, Masahito Yamada, Masaru Mimura, Kenji Nakashima, Takaaki Mori, Minoru Takebayashi, Tomoyuki Ohara, Jun Hata, Yoshihiro Kokubo, Kazuhiro Uchida, Yasuyuki Taki, Shuzo Kumagai, Koji Yonemoto, Hisako Yoshida, Kaori Muto, Yukihide Momozawa, Masato Akiyama, Michiaki Kubo, Manabu Ikeda, Shigenobu Kanba, Yutaka Kiyohara, Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD)., Environmental health and preventive medicine, 10.1186/s12199-020-00903-3, 25, 1, 64-64, 2020.10, BACKGROUND: The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. METHODS: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. RESULTS: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer's disease. CONCLUSIONS: The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.. |
| 126. | Mao Shibata, Tomoyuki Ohara, Masako Hosoi, Hata Jun, Daigo Yoshida, Naoki Hirabayashi, Yukiko Morisaki, Taro Nakazawa, Akane Mihara, Takuya Nagata, Emi Oishi, Kozo Anno, Nobuyuki Sudo, Toshiharu Ninomiya, Emotional loneliness is associated with a risk of dementia in a general Japanese older population: the Hisayama Study., The journals of gerontology. Series B, Psychological sciences and social sciences, 10.1093/geronb/gbaa196, 76, 9, 1756-1766, 2020.11, OBJECTIVES: To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population. METHOD: A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales-namely, social and emotional loneliness-by using the 6-Item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression. RESULTS: During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95% confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08-2.40) and 1.65 (1.07-2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives. DISCUSSION: The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan.. |
| 127. | Takuya Nagata, Jun Hata, Satoko Sakata, Emi Oishi, Takanori Honda, Yoshihiko Furuta, Tomoyuki Ohara, Daigo Yoshida, Yoichiro Hirakawa, Mao Shibata, Tomomi Ide, Takanari Kitazono, Hiroyuki Tsutsui, Toshiharu Ninomiya, Serum N-terminal pro-B-type natriuretic peptide as a predictor for future development of atrial fibrillation in a general population: the Hisayama Study., International journal of cardiology, 10.1016/j.ijcard.2020.06.018, 320, 90-96, 2020.12, BACKGROUND: Biomarkers for predicting future development of atrial fibrillation (AF) have not been fully established in general populations. The aim of this study was to assess the predictive ability of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) for the development of AF. METHODS AND RESULTS: A total of 3126 community-dwelling Japanese subjects aged ≥ 40 years without a history of AF in 2002 were followed up for a median of 10.2 years. Serum NT-proBNP levels at baseline were divided into four categories (≤ 54, 55-124, 125-299, and ≥ 300 pg/mL) according to the current guidelines and prior reports. The hazard ratios for the development of AF were estimated using a Cox proportional hazards model. During the follow-up period, 153 subjects developed new-onset AF. The age- and sex-adjusted cumulative incidence of AF increased significantly with higher serum NT-proBNP levels (p |
| 128. | Sanmei Chen, Takanori Honda, Jun Hata, Satoko Sakata, Yoshihiko Furuta, Daigo Yoshida, Mao Shibata, Tomoyuki Ohara, Yoichiro Hirakawa, Emi Oishi, Takanari Kitazono, Toshiharu Ninomiya, High Serum Folate Concentrations Are Associated with Decreased Risk of Mortality among Japanese Adults., The Journal of nutrition, 10.1093/jn/nxaa382, 151, 3, 657-665, 2021.03, BACKGROUND: Folate and vitamin B-12 are essential nutrients for normal cell growth and replication, but the association of serum folate and vitamin B-12 concentrations with mortality risk remains uncertain. OBJECTIVE: This study was performed to investigate the associations of serum folate and vitamin B-12 concentrations with mortality risk and test whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism modifies these associations. METHODS: A total of 3050 Japanese community residents aged ≥40 y were prospectively followed-up for mortality between 2002 and 2012. Cox proportional hazards models and restricted cubic splines were used to estimate HRs and 95% CIs of mortality. RESULTS: During a median follow-up period of 10.2 y, 336 participants died. Higher serum folate concentrations were associated with lower risks of all-cause mortality [multivariable-adjusted HR: 0.73; 95% CI: 0.56, 0.96 for the second tertile (8.8-12.2 nmol/L; median 10.4 nmol/L) and HR: 0.61; 95% CI: 0.46, 0.80 for the third tertile (≥12.5 nmol/L; median 15.6 nmol/L) serum folate concentrations compared with the first tertile (≤8.6 nmol/L; median 7.0 nmol/L)]. This association remained significant in all sensitivity analyses. Spline analyses showed a steady decline in all-cause mortality risk with increasing serum folate concentrations up to 20-25 nmol/L. This association persisted regardless of the MTHFR C677T genotypes. For serum vitamin B-12, the multivariable-adjusted HR of 1.32 (95% CI: 0.97, 1.79) of all-cause mortality was marginally significantly greater in the first tertile compared with the second tertile. This association was attenuated and nonsignificant after the exclusion of participants with a history of cardiovascular disease or cancer, or participants aged ≥85 y at baseline, or deaths in the first 3 y of follow-up. CONCLUSIONS: Serum folate concentrations were inversely associated with the risk of all-cause mortality in Japanese adults. Serum vitamin B-12 concentrations were not consistently associated with all-cause mortality risk after accounting for reverse-causation bias.. |
| 129. | Kimitaka Nakamura, Daigo Yoshida, Takanori Honda, Jun Hata, Mao Shibata, Yoichiro Hirakawa, Yoshihiko Furuta, Hiro Kishimoto, Tomoyuki Ohara, Sanmei Chen, Takanari Kitazono, Yasuharu Nakashima, Toshiharu Ninomiya, Midlife and late-life diabetes and sarcopenia in a general older Japanese population: The Hisayama Study., Journal of diabetes investigation, 10.1111/jdi.13550, 12, 10, 1899-1907, 2021.03, AIMS/INTRODUCTION: To investigate the association between midlife or late-life diabetes and the development of sarcopenia in an older Japanese population. MATERIALS AND METHODS: A total of 824 Japanese residents aged 65 to 84 years without sarcopenia were followed up from 2012 to 2017. Sarcopenia was determined following the Asian Working Group for Sarcopenia definition. The time of diabetes diagnosis was classified as midlife or late-life diabetes by the age at first diagnosis of diabetes ( 15 years. The odds ratios of incident sarcopenia according to the diabetic status were estimated using a logistic regression analysis. RESULTS: During follow-up, 47 subjects developed sarcopenia. The multivariable-adjusted odds ratio for incident sarcopenia was significantly greater in subjects with diabetes at baseline than in those without it (odds ratio 2.51, 95% confidence interval 1.26-5.00). Subjects with midlife diabetes had a significantly greater risk of incident sarcopenia, whereas no significant association between late-life diabetes and incident sarcopenia was observed. With a longer duration of diabetes, the risk of incident sarcopenia increased significantly (P for trend = 0.002). CONCLUSIONS: The present study suggests that midlife diabetes and a longer duration of diabetes are significant risk factors for incident sarcopenia in the older population. Preventing diabetes in midlife may reduce the risk of the development of sarcopenia in later life.. |
| 130. | Tomoyuki Ohara, Daigo Yoshida, Jun Hata, Mao Shibata, Takanori Honda, Yoshihiko Furuta, Naoki Hirabayashi, Takanari Kitazono, Tomohiro Nakao, Toshiharu Ninomiya, Current status of the certification of long-term care insurance among individuals with dementia in a Japanese community: The Hisayama Study., Psychiatry and clinical neurosciences, 10.1111/pcn.13204, 75, 5, 182-184, 2021.05. |
| 131. | Kimitaka Nakamura, Daigo Yoshida, Takanori Honda, Jun Hata, Mao Shibata, Yoichiro Hirakawa, Yoshihiko Furuta, Hiro Kishimoto, Tomoyuki Ohara, Takanari Kitazono, Yasuharu Nakashima, Toshiharu Ninomiya, Prevalence and Mortality of Sarcopenia in a Community-dwelling Older Japanese Population: The Hisayama Study., Journal of epidemiology, 10.2188/jea.JE20190289, 31, 5, 320-327, 2021.05, BACKGROUND: The prevalence of sarcopenia defined using the Asian Working Group for Sarcopenia (AWGS) criteria in Asian communities has not been fully addressed. Moreover, few studies have addressed the influence of sarcopenia on mortality. METHODS: A total of 1,371 and 1,597 residents aged 65 years or older participated in health surveys in 2012 and 2017. Sarcopenia was determined using the AWGS definition. Factors associated with the presence of sarcopenia were assessed using a logistic regression model in participants in the 2012 survey. Subjects in the 2012 survey were followed-up prospectively for a median of 4.3 years. Mortality risk for subjects with sarcopenia was examined using the Cox proportional hazards model. RESULTS: The crude prevalence of sarcopenia was 7.4% and 6.6% in participants at the 2012 and 2017 surveys, respectively; there was no significant difference between surveys (P = 0.44). The prevalence of sarcopenia increased significantly with age in both sexes (both P for trend |
| 132. | Nakamura K, Yoshida D, Honda T, Hata J, Shibata M, Hirakawa Y, Furuta Y, Kishimoto H, Ohara T, Chen S, Kitazono T, Nakashima Y, Ninomiya T, Midlife and late-life diabetes and sarcopenia in a general older Japanese population: the Hisayama Study., J Diabetes Investig, 12, 10, 1899-1907, 2021.05. |
| 133. | Oishi E, Hata J, Honda T, Sakata S, Chen S, Hirakawa Y, Yoshida D, Shibata M, Ohara T, Furuta Y, Kitazono T, Ninomiya T, Development of a risk prediction model for incident hypertension in Japanese individuals: the Hisayama Study., Hypertens Res, 14, 9, 1221-1229, 2021.05. |
| 134. | 多治見 昂洋, 古田 芳彦, 平林 直樹, 本田 貴紀, 秦 淳, 小原 知之, 柴田 舞欧, 中尾 智博, 北園 孝成, 中島 康晴, 二宮 利治, 地域高齢住民における歩行速度と認知症発症および脳容積との関連 久山町研究, 日本整形外科学会雑誌, 95, 8, S1723-S1723, 2021.08. |
| 135. | 多治見 昂洋, 古田 芳彦, 平林 直樹, 本田 貴紀, 秦 淳, 小原 知之, 柴田 舞欧, 中尾 智博, 北園 孝成, 中島 康晴, 二宮 利治, 地域高齢住民における歩行速度と認知症発症および脳容積との関連 久山町研究, 日本整形外科学会雑誌, 95, 8, S1723-S1723, 2021.08. |
| 136. | Emi Oishi, Jun Hata, Takanori Honda, Satoko Sakata, Sanmei Chen, Yoichiro Hirakawa, Daigo Yoshida, Mao Shibata, Tomoyuki Ohara, Yoshihiko Furuta, Takanari Kitazono, Toshiharu Ninomiya, Development of a risk prediction model for incident hypertension in Japanese individuals: the Hisayama Study., Hypertension research : official journal of the Japanese Society of Hypertension, 10.1038/s41440-021-00673-7, 44, 9, 1221-1229, 2021.09, The identification of individuals at high risk of developing hypertension can be of great value to improve the efficiency of primary prevention strategies for hypertension. The objective of this study was to develop a risk prediction model for incident hypertension based on prospective longitudinal data from a general Japanese population. A total of 982 subjects aged 40-59 years without hypertension at baseline were followed up for 10 years (2002-12) for the incidence of hypertension. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or the use of antihypertensive agents. The risk prediction model was developed using a Cox proportional hazards model. A simple risk scoring system was also established based on the developed model. During the follow-up period (median 10 years, interquartile range 5-10 years), 302 subjects (120 men and 182 women) developed new-onset hypertension. The risk prediction model for hypertension consisted of age, sex, SBP, DBP, use of glucose-lowering agents, body mass index (BMI), parental history of hypertension, moderate-to-high alcohol intake, and the interaction between age and BMI. The developed model demonstrated good discrimination (Harrell's C statistic=0.812 [95% confidence interval, 0.791-0.834]; optimism-corrected C statistic based on 200 bootstrap samples=0.804) and calibration (Greenwood-Nam-D'Agostino χ2 statistic=12.2). This risk prediction model is a useful guide for estimating an individual's absolute risk for hypertension and could facilitate the management of Japanese individuals at high risk of developing hypertension in the future.. |
| 137. | Erika Castillo, Julio Leon, Guianfranco Mazzei, Nona Abolhassani, Naoki Haruyama, Takashi Saito, Takaomi Saido, Masaaki Hokama, Toru Iwaki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Kunihiko Sakumi, Frank M LaFerla, Yusaku Nakabeppu, Author Correction: Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation., Scientific reports, 10.1038/s41598-021-97918-9, 11, 1, 18377-18377, 2021.09. |
| 138. | Taro Nakazawa, Tomoyuki Ohara, Naoki Hirabayashi, Yoshihiko Furuta, Jun Hata, Mao Shibata, Takanori Honda, Takanari Kitazono, Tomohiro Nakao, Toshiharu Ninomiya, Multiple-region grey matter atrophy as a predictor for the development of dementia in a community: the Hisayama Study, Journal of Neurology, Neurosurgery & Psychiatry, 10.1136/jnnp-2021-326611, jnnp-2021, 2021.10, |
| 139. | Hamasaki H, Shijo M, Nakamura A, Honda H, Yamada Y, Oda Y, Ohara T, Ninomiya T, Iwaki T, Concurrent cardiac transthyretin and brain β amyloid accumulation among the older adults: the Hisayama study, Brain Pathol, 32, 1, e13014, 2022.01. |
| 140. | Noguchi-Shinohara M, Yuki-Nozaki S, Abe C, Mori A, Horimoto M, Yokogawa M, Ishida N, Suga Y, Ishizaki J, Ishimiya M, Nakamura H, Komai K, Nakamura H, Shibata M, Ohara T, Hata J, Ninomiya T, Yamada M, Diabetes mellitus, elevated hemoglobin A1c, and glycated albumin are associated with the presence of all-cause dementia and Alzheimer's disease: the JPSC-AD Study., J Alzheimers Dis, 85, 1, 235-247, 2022.01. |
| 141. | Yagita K, Honda H, Ohara T, Hamasaki H, Koyama S, Noguchi H, Mihara A, Nakazawa T, Hata J, Ninomiya T, Iwaki T, A comparative study of site-specific distribution of aging-related tau astrogliopathy and its risk factors between Alzheimer disease and cognitive healthy brains: the Hisayama Study., J Neuropathol Exp Neurol , 81, 2, 106-116, 2022.01. |
| 142. | Kaoru Yagita, Hiroyuki Honda, Tomoyuki Ohara, Hideomi Hamasaki, Sachiko Koyama, Hideko Noguchi, Akane Mihara, Taro Nakazawa, Jun Hata, Toshiharu Ninomiya, Toru Iwaki, A Comparative Study of Site-Specific Distribution of Aging-Related Tau Astrogliopathy and Its Risk Factors Between Alzheimer Disease and Cognitive Healthy Brains: The Hisayama Study., Journal of neuropathology and experimental neurology, 10.1093/jnen/nlab126, 81, 2, 106-116, 2022.01, Knowledge of aging-related tau astrogliopathy (ARTAG) in healthy elderly individuals remains incomplete and studies to date have not focused on the olfactory nerve, which is a vulnerable site of various neurodegenerative disease pathologies. We performed a semiquantitative evaluation of ARTAG in 110 autopsies in the Japanese general population (Hisayama study). Our analysis focused on Alzheimer disease (AD) and cognitive healthy cases (HC), including primary age-related tauopathy. Among the various diseased and nondiseased brains, ARTAG was frequently observed in the amygdala. The ARTAG of HC was exclusively limited to the amygdala whereas gray matter ARTAG in AD cases was prominent in the putamen and middle frontal gyrus following the amygdala. ARTAG of the olfactory nerve mainly consists of subpial pathology that was milder in the amygdala. A logistic regression analysis revealed that age at death and neurofibrillary tangle Braak stage significantly affected the ARTAG of HC. In AD, age at death and male gender had significant effects on ARTAG. In addition, the Thal phase significantly affected the presence of white matter ARTAG. In conclusion, our research revealed differences in the distribution of ARTAG and affected variables across AD and HC individuals.. |
| 143. | Hideomi Hamasaki, Masahiro Shijo, Ayaka Nakamura, Hiroyuki Honda, Yuichi Yamada, Yoshinao Oda, Tomoyuki Ohara, Toshiharu Ninomiya, Toru Iwaki, Concurrent cardiac transthyretin and brain β amyloid accumulation among the older adults: The Hisayama study., Brain pathology (Zurich, Switzerland), 10.1111/bpa.13014, 32, 1, e13014, 2022.01, Previous studies have revealed risk for cognitive impairment in cardiovascular diseases. We investigated the relationship between degenerative changes of the brain and heart, with reference to Alzheimer's disease (AD) pathologies, cardiac transthyretin amyloid (ATTR) deposition, and cardiac fibrosis. A total of 240 consecutive autopsy cases of a Japanese population-based study were examined. β amyloid (Aβ) of senile plaques, phosphorylated tau protein of neurofibrillary tangles, and ATTR in the hearts were immunohistochemically detected and graded according to the NIH-AA guideline for AD pathology and as Tanskanen reported, respectively. Cerebral amyloid angiopathy (CAA) was graded according to the Vonsattel scale. Cardiac fibrosis was detected by picrosirius red staining, followed by image analysis. Cardiac ATTR deposition occurred after age 75 years and increased in an age-dependent manner. ATTR deposition was more common, and of higher grades, in the dementia cases. We subdivided the cases into two age groups: ≤90 years old (n = 173) and >90 years old (n = 67), which was the mean and median age at death of the AD cases. When adjusted for age and sex, TTR deposition grades correlated with Aβ phase score (A2-3), the Consortium to Establish a Registry for AD score (sparse to frequent), and high Braak stage (V-VI) only in those aged ≤90 years at death. No significant correlation was observed between the cardiac ATTR deposition and CAA stages, or between cardiac fibrosis and AD pathologies. Collectively, AD brain pathology correlated with cardiac TTR deposition among the older adults ≤90 years.. |
| 144. | Nakazawa T, Ohara T, Hirabayashi N, Furuta Y, Hata J, Shibata M, Honda T, Kitazono T, Nakao T, Ninomiya T, Multiple-region grey matter atrophy as a predictor for the development of dementia in a community: the Hisayama Study., J Neurol Neurosurg Psychiatry, 93, 3, 263-271, 2022.03. |
| 145. | Masako Asada, Mao Shibata, Naoki Hirabayashi, Tomoyuki Ohara, Yoshihiko Furuta, Taro Nakazawa, Takanori Honda, Jun Hata, Masako Hosoi, Nobuyuki Sudo, Ken Yamaura, Toshiharu Ninomiya, Association between chronic low back pain and regional brain atrophy in a Japanese older population: the Hisayama Study., Pain, 10.1097/j.pain.0000000000002612, 163, 11, 2185-2193, 2022.03, ABSTRACT: Chronic low back pain (CLBP) is the leading cause of years lived with disability. Recently, it has been reported that CLBP is associated with alterations in the central nervous system. The present study aimed to investigate the association between CLBP and regional brain atrophy in an older Japanese population. A total of 1106 community-dwelling participants aged ≥65 years underwent brain magnetic resonance imaging scans and a health examination in 2017 to 2018. We used the FreeSurfer software for the analysis of brain magnetic resonance imaging. Chronic pain was defined as subjective pain for ≥3 months. Participants were divided into 3 groups according to the presence or absence of chronic pain and the body part that mainly suffered from pain: a "no chronic pain (NCP)" group (n = 541), "CLBP" group (n = 189), and "chronic pain in body parts other than the lower back (OCP)" group (n = 376). The brain volumes of the ventrolateral and dorsolateral prefrontal cortex, the posterior cingulate gyrus, and the amygdala were significantly lower in the CLBP group than in the NCP group after adjustment for sociodemographic, physical, and lifestyle factors and depressive symptoms. In addition, the left superior frontal gyrus was identified as a significant cluster by the Query, Design, Estimate, Contrast interface. There were no significant differences in the brain volumes of pain-related regions between the NCP and the OCP groups. The present study suggests that CLBP is associated with lower brain volumes of pain-related regions in a general older population of Japanese.. |
| 146. | Tomoyuki Ohara, Jun Hata, Masashi Tanaka, Takanori Honda, Hajime Yamakage, Takayuki Inoue, Yoichiro Hirakawa, Toru Kusakabe, Mao Shibata, Takanari Kitazono, Tomohiro Nakao, Noriko Satoh-Asahara, Toshiharu Ninomiya, Association of daily sleep duration with the incident dementia by serum soluble TREM2 in a community., Journal of the American Geriatrics Society, 10.1111/jgs.17634, 70, 4, 1147-1156, 2022.04, BACKGROUND: Little is known about the influence of serum level of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which is a soluble type of an innate immune receptor expressed on the microglia, on the association of the daily sleep duration with the risk of dementia. METHODS: A total of 1230 Japanese community-residents aged 60 and older without dementia were followed prospectively for 10 years (2002-2012). Serum sTREM2 levels were divided into two groups using the median value (334.8 pg/ml). Self-reported daily sleep duration was grouped into three categories of |
| 147. | Naoki Hirabayashi, Jun Hata, Yoshihiko Furuta, Tomoyuki Ohara, Mao Shibata, Yoichiro Hirakawa, Fumio Yamashita, Kazufumi Yoshihara, Takanari Kitazono, Nobuyuki Sudo, Toshiharu Ninomiya, Association Between Diabetes and Gray Matter Atrophy Patterns in a General Older Japanese Population: The Hisayama Study., Diabetes care, 10.2337/dc21-1911, 45, 6, 1364-1371, 2022.05, OBJECTIVE: To examine the association between diabetes and gray matter atrophy patterns in a general older Japanese population. RESEARCH DESIGN AND METHODS: In 2012, a total of 1,189 community-dwelling Japanese aged ≥65 years underwent brain MRI scans. Regional gray matter volumes (GMV) and intracranial volume (ICV) were measured by applying voxel-based morphometry (VBM) methods. The associations of diabetes and related parameters with the regional GMV/ICV were examined using an ANCOVA. The regional gray matter atrophy patterns in the subjects with diabetes or elevated fasting plasma glucose (FPG) or 2 h postload glucose (2hPG) levels were investigated using VBM. RESULTS: Subjects with diabetes had significantly lower mean values of GMV/ICV in the frontal lobe, temporal lobe, insula, deep gray matter structures, and cerebellum than subjects without diabetes after adjusting for potential confounders. A longer duration of diabetes was also significantly associated with lower mean values of GMV/ICV in these brain regions. The multivariable-adjusted mean values of the temporal, insular, and deep GMV/ICV decreased significantly with elevating 2hPG levels, whereas higher FPG levels were not significantly associated with GMV/ICV of any brain regions. In the VBM analysis, diabetes was associated with gray matter atrophy in the bilateral superior temporal gyri, right middle temporal gyrus, left inferior temporal gyrus, right middle frontal gyrus, bilateral thalami, right caudate, and right cerebellum. CONCLUSIONS: The current study suggests that a longer duration of diabetes and elevated 2hPG levels are significant risk factors for gray matter atrophy in various brain regions.. |
| 148. | Akane Mihara, Tomoyuki Ohara, Jun Hata, Sanmei Chen, Takanori Honda, Sonam Tamrakar, Akiko Isa, Dongmei Wang, Kuniyoshi Shimizu, Yoshinori Katakura, Koji Yonemoto, Tomohiro Nakao, Takanari Kitazono, Toshiharu Ninomiya, Association of serum s-adenosylmethionine, s-adenosylhomocysteine, and their ratio with the risk of dementia and death in a community., Scientific reports, 10.1038/s41598-022-16242-y, 12, 1, 12427-12427, 2022.07, We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007-2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death.. |
| 149. | Takahiro Tajimi, Yoshihiko Furuta, Naoki Hirabayashi, Takanori Honda, Jun Hata, Tomoyuki Ohara, Mao Shibata, Tomohiro Nakao, Takanari Kitazono, Yasuharu Nakashima, Toshiharu Ninomiya, Association of gait speed with regional brain volumes and risk of dementia in older Japanese: The Hisayama study., Archives of gerontology and geriatrics, 10.1016/j.archger.2022.104883, 106, 104883-104883, 2022.12, BACKGROUND: To investigate the association of gait speed with regional brain volumes and the risk of incident dementia. METHODS: A total of 1112 dementia-free Japanese residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years (median). The participants were classified into the age- and sex-specific quartile levels of maximum gait speed. Regional gray matter volumes (GMV) and white matter hyperintensities volumes (WMHV) were measured by applying voxel-based morphometry methods. The cross-sectional association of maximum gait speed with regional GMV was examined using an analysis of covariance. We also estimated the association between maximum gait speed level and the risk of developing dementia using a Cox proportional hazards model. Mediation analyses were conducted to determine the contribution of regional brain volumes to the association between maximum gait speed and dementia. RESULTS: Lower maximum gait speed was significantly associated with lower GMV of the total brain, frontal lobe, temporal lobe, cingulate gyrus, insula, hippocampus, amygdala, basal ganglia, thalamus, and cerebellum, and increased WMHV at baseline. During the follow-up, 108 participants developed dementia. The incidence rate of all dementias increased significantly with decreasing maximum gait speed after adjusting for potential confounders (P for trend = 0.03). The mediating effects of the GMV of the hippocampus, GMV of the insula, and WMHV were significant. CONCLUSIONS: Lower maximum gait speed was significantly associated with an increased risk of dementia. Reduced GMV of the hippocampus or insula, and an increase in WMHV was likely to be involved in this association.. |
| 150. | Yasumi Kimura, Daigo Yoshida, Tomoyuki Ohara, Jun Hata, Takanori Honda, Yoichiro Hirakawa, Mao Shibata, Emi Oishi, Satoko Sakata, Yoshihiko Furuta, Sanmei Chen, Kazuhiro Uchida, Tomohiro Nakao, Takanari Kitazono, Toshiharu Ninomiya, Long-term association of vegetable and fruit intake with risk of dementia in Japanese older adults: the Hisayama study, BMC Geriatrics, 10.1186/s12877-022-02939-2, 22, 1, 2022.12, Abstract Background Several prospective Western studies have reported an inverse association of vegetable and fruit intake with dementia risk. However, there is limited epidemiologic evidence in Asians. This study investigated the association of intakes of vegetables, fruits, and their nutrients on the risk of incident dementia and its subtypes in a Japanese community. Methods A total of 1071 participants (452 men and 619 women) aged ≥60 years without dementia at baseline were prospectively followed up for 24 years. Intakes of vegetables, fruits, and nutrients were evaluated using a 70-item semiquantitative food frequency questionnaire at baseline and were categorized into quartiles separately by gender. The outcome measure was the development of dementia and its subtypes—namely, Alzheimer’s disease (AD) and vascular dementia (VaD). The risk estimates of incident dementia were computed using a Cox proportional hazards model. Results During the long-term follow-up period, 464 subjects developed dementia, of whom 286 had AD and 144 had VaD. Higher vegetable intake was associated gradually with lower risk of developing dementia and AD (both P-trend Conclusion Higher intakes of vegetables and their constituent nutrients were associated with a lower risk of dementia in Japanese older adults. A diet rich in vegetables may be beneficial in reducing the dementia risk in Asians.. |
| 151. | Kenji Maki, Tomoyuki Ohara, Jun Hata, Mao Shibata, Naoki Hirabayashi, Takanori Honda, Satoko Sakata, Yoshihiko Furuta, Masato Akiyama, Keisuke Yamasaki, Yasuko Tatewaki, Yasuyuki Taki, Takanari Kitazono, Tatsuya Mikami, Tetsuya Maeda, Kenjiro Ono, Masaru Mimura, Kenji Nakashima, Jun-Ichi Iga, Minoru Takebayashi, Toshiharu Ninomiya, CKD, Brain Atrophy, and White Matter Lesion Volume: The Japan Prospective Studies Collaboration for Aging and Dementia., Kidney medicine, 10.1016/j.xkme.2022.100593, 5, 3, 100593-100593, 2023.03, RATIONALE & OBJECTIVE: Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. STUDY DESIGN: Population-based cross-sectional study. SETTING & PARTICIPANTS: A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. EXPOSURES: UACR and eGFR levels. OUTCOMES: The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). ANALYTICAL APPROACH: The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. RESULTS: Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend = 0.009 and |
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