To determine whether the diffusion abnormalities in brains with Alzheimer's disease (AD) correlate with disease severity, we studied 34 AD patients using diffusion tensor MRI. Mean diffusivity and fractional anisotropy (FA) as well as three eigenvalues (lambda1, lambda2, and lambda3) of the diffusion tensor of the posterior cingulate white matter correlated with the Mini-Mental State Examination (MMSE) score. The mean diffusivity and the three eigenvalues showed significant correlation with the MMSE score. On the other hand, no significant correlation was seen between the FA and MMSE score. Our results suggested that mean diffusivity and the eigen-values, but not FA, reflect progression of AD-related histopathlogical changes in the posterior cingulate white matter and may be useful biological indices to monitor AD.

Objectives: To study the factors which influence cognitive impairment among elderly subjects living in a local community, based on both MRI and clinical findings, to further elucidate the causes of dementia, and also to help develop strategies for its prevention. Methods: Cranial MRI and other medical examinations were performed on non-demented elderly subjects who resided in one rural community. A total of 254 subjects aged from 60 to 91 years of age, with a mean age of 73.9 (SD 6.8) were examined. The mini mental state examination (MMSE) was used to identify cognitive impairment. White matter lesions and cerebral atrophy on MR images were measured quantitatively. A multivariate analysis was also performed with the existence of cognitive impairment as the dependent variable, and the MRI findings and clinical observations were used as the independent variables. Results: Cognitive impairment was present in 46 subjects (18.1%). They were older, had a lower educational level, and more frequent hypertension compared with those without cognitive impairment. The packed cell volume was lower in the impaired group. In addition, their MRI findings showed significantly larger quantities of white matter lesions and cerebral atrophy, as well as more infarcts. A logistic regression analysis demonstrated a significant relation among such factors as white matter lesions (odds ratio (OR) 1.575, 95% confidence interval (95% CI) 1.123-2.208), cerebral atrophy (OR 0.761, 95%CI 0.587-0.987), and lower education (OR 0.682, 95%CI 0.544-0.855) for subjects with a cognitive impairment. Conclusions: White matter lesions and cerebral atrophy are factors which induce a cognitive impairment in community dwelling elderly subjects without dementia. It is important to carefully watch for any abnormalities in these factors, and to perform cohort studies to check for the above risk factors, to both prevent and make an early diagnosis of dementia. E lucidating the causes of dementia as well as making an early diagnosis, and developing strategies to prevent dementia are matters of extreme urgency in our aging society. So far several reports have been published on large scale examinations of the general population to investigate the course of dementia before and after its onset. [1][2][3][4][5][6] There are also many reports about the influence of certain specific risk factors, such as white matter lesions, silent cerebral infarction, and other risk factors related to cognitive function. However, there have been few comprehensive studies which focus on cognitive impairment and the factors which influence them, based on both clinical observation and image examinations. In the present study, we performed cranial MRI and other procedures in elderly subjects who lead a normal life at home and investigated the factors influencing cognitive function based on a multivariate analysis. In particular, abnormal findings on MRI such as white matter lesions and cerebral atrophy were measured quantitatively. We herein report our findings which led to the conclu...

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To clarify the association of microglia with senile plaques, the brains from 13 patients with Alzheimer's disease (AD) and 23 nondemented aged controls were investigated immunohistochemically by a double-labeling method using anti-beta-protein antiserum and anti-ferritin antibody, which is a recently reported microglia marker. In addition, a quantitative analysis was performed. The senile plaques which appeared initially in the nondemented aged controls consisted of a diffuse type without any amyloid cores and these were found in the group aged 50-59 years. The great majority of them were found to contain no ferritin-positive microglia. The number and proportion (percentage) of microglia-containing diffuse plaques increased with age. Classical and compact plaques began to appear in the brains of the group aged 70 years and over, and practically all of them contained microglia. These results suggest that microglia are not associated with initial plaque formation, but correlate with amyloid core formation. In AD, the most prominent feature was that the diffuse plaques, which contained either no or only a few ferritin-positive microglia, increased markedly.