Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study.

OBJECTIVE: We examined the association between diabetes-related factors and pathology of Alzheimer disease (AD) to evaluate how diabetes affects the pathogenic process of AD. METHODS: This study included specimens from a series of 135 autopsies of residents of the town of Hisayama in Fukuoka prefecture (74 men and 61 women) performed between 1998 and 2003, who underwent a 75-g oral glucose tolerance test in clinical examinations in 1988. We measured diabetes-related factors including fasting glucose, 2-hour post-load plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 1988. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines and neurofibrillary tangles (NFTs) were assessed according to Braak stage. The associations between each factor and AD pathology were examined by analysis of covariance and logistic regression analyses. RESULTS: Higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were associated with increased risk for NPs after adjustment for age, sex, systolic blood pressure, total cholesterol, body mass index, habitual smoking, regular exercise, and cerebrovascular disease. However, there were no relationships between diabetes-related factors and NFTs. Regarding the effects of APOE genotype on the risk of AD pathology, the coexistence of hyperglycemia and APOE epsilon4 increased the risk for NP formation. A similar enhancement was observed for hyperinsulinemia and high HOMA-IR. CONCLUSION: The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE epsilon4.

Trends in prevalence of Alzheimer's disease and vascular dementia in a Japanese community: the Hisayama Study.

OBJECTIVE: To examine secular trends in the prevalence of Alzheimer's disease (AD) and vascular dementia (VD) in a general Japanese population. METHOD: Four cross-sectional examinations were conducted among residents of a Japanese community aged >or=65 in 1985, 1992, 1998 and 2005. RESULTS: The age- and sex-adjusted prevalence of all-cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age- and sex-adjusted prevalence of VD and other/unclassified dementia showed J-shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005). CONCLUSION: Our findings suggest that the prevalence of all-cause dementia and AD significantly increased over the past two decades in the general Japanese population.