Visual assessment of MTA on brain MRI using a standardized rating scale is a powerful and independent predictor of conversion to dementia in relatively young MCI patients. As overlap existed in MTA scores between patients with and without dementia at follow-up, the results should be interpreted in the light of the odds for the individual patient.

Abstract-Hippocampal atrophy (HA) is usually attributed to the neurofibrillary tangles and neuritic plaques of Alzheimer disease. However, the hippocampus is vulnerable to global ischemia, which may lead to atrophy. We investigated the association of midlife blood pressure (BP) and late-life HA in a sample of Japanese-

OBJECTIVE -Type 2 diabetes leads to cognitive impairment and dementia, which may reflect microvascular and macrovascular complications as well as neurodegenerative processes. There are few studies on the anatomical basis for loss of cognitive function in type 2 diabetes. The objective of this study was to investigate the association between type 2 diabetes and markers of brain aging on magnetic resonance images, including infarcts, lacunes, and white matter hyperintensities as markers of vascular damage and general and hippocampal atrophy as markers of neurodegeneration in Japanese-American men born between 1900 and 1919 and followed since 1965 in the Honolulu-Asia Aging Study.RESEARCH DESIGN AND METHODS -Prevalent and incident dementia was assessed. Associations between magnetic resonance imaging markers and diabetic status were estimated with logistic regression, controlling for sociodemographic and other vascular factors.RESULTS -The prevalence of type 2 diabetes in the cohort is 38%. Subjects with type 2 diabetes had a moderately elevated risk for lacunes (odds ratio [OR] 1.6 [95% CI 1.0 -2.6]) and hippocampal atrophy (1.7 [0.9 -2.9]). The risk for both hippocampal atrophy and lacunes/ infarcts was twice as high in subjects with compared with those without type 2 diabetes. Among the group with type 2 diabetes, those with the longest duration of diabetes, those taking insulin, and those with complications had relatively more pathologic brain changes.CONCLUSIONS -There is evidence that older individuals with type 2 diabetes have an elevated risk for vascular brain damage and neurodegenerative changes. These pathological changes may be the anatomical basis for an increased risk of cognitive impairment or dementia in type 2 diabetes. Diabetes Care 29:2268 -2274, 2006S ubjects with type 2 diabetes are at increased risk for cerebral complications, including stroke (1,2), cognitive impairment (3,4), and dementia (5-7). This may partially reflect the systemic microvascular (retinopathy, nephropathy, and neuropathy) (8) and macrovascular (coronary heart disease and peripheral arterial disease) (9 -11) complications that characterize type 2 diabetes. Characteristics of subjects with type 2 diabetes, such as hyperglycemia, elevated blood pressure, hyperinsulinemia, and dyslipidemia may also directly affect neuronal viability. In type 2 diabetes, the phosphorylation of tau may be enhanced (12), the breakdown of amyloid might be diminished (13,14), and advanced glycated end products may contribute to the formation of neurofibrillary tangles (NFTs) and neuritic plaques (15), which are markers of Alzheimer's disease, a major neurodegenerative disease in the elderly. Autopsy data based on the Honolulu-Asia Aging Study (HAAS) cohort show a significant association of type 2 diabetes with infarcts as well as hippocampal NFTs and neuritic plaques (6).Taken together, the evidence suggests that type 2 diabetes may contribute to cognitive disorders not only via vascular lesions but also via neurodegeneration. To test this hypothes...