Brain infarction and the clinical expression of Alzheimer disease. The Nun Study

D. A. Snowdon, L. H. Greiner, J. A. Mortimer, K. P. Riley, P. A. Greiner and W. R. Markesbery
Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.

OBJECTIVE: To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD). DESIGN: Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD. SETTING: Convents in the Midwestern, Eastern, and Southern United States. PARTICIPANTS: A total of 102 college-educated women aged 76 to 100 years. MAIN OUTCOME MEASURES: Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria. RESULTS: Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts. CONCLUSION: These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.

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