OBJECTIVE: To examine the relation of National Institute on Aging-Reagan (NIA-Reagan) neuropathologic criteria of Alzheimer disease (AD) to level of cognitive function in persons without dementia or mild cognitive impairment (MCI). METHODS: More than 2,000 persons without dementia participating in the Religious Orders Study or the Memory and Aging Project agreed to annual detailed clinical evaluation and brain donation. The studies had 19 neuropsychological performance tests in common that assessed five cognitive domains, including episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. A total of 134 persons without cognitive impairment died and underwent brain autopsy and postmortem assessment for AD pathology using NIA-Reagan neuropathologic criteria for AD, cerebral infarctions, and Lewy bodies. Linear regression was used to examine the relation of AD pathology to level of cognitive function proximate to death. RESULTS: Two (1.5%) persons met NIA-Reagan criteria for high likelihood AD, and 48 (35.8%) met criteria for intermediate likelihood; 29 (21.6%) had cerebral infarctions, and 18 (13.4%) had Lewy bodies. The mean Mini-Mental State Examination score proximate to death was 28.2 for those meeting high or intermediate likelihood AD by NIA-Reagan criteria and 28.4 for those not meeting criteria. In linear regression models adjusted for age, sex, and education, persons meeting criteria for intermediate or high likelihood AD scored about a quarter standard unit lower on tests of episodic memory (p = 0.01). There were no significant differences in any other cognitive domain. CONCLUSIONS: Alzheimer disease pathology can be found in the brains of older persons without dementia or mild cognitive impairment and is related to subtle changes in episodic memory.
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