Neuropathological and neuropsychological changes in "normal" aging: Evidence for preclinical Alzheimer disease in cognitively normal individuals

The presence of diffuse or primitive senile plaques in the neocortex of cog nitively normal elderly at autopsy has been presumed to represent normal ag ing. Alternatively, these patients may have developed dementia and clinical Alzheimer disease (AD) if they had survived. In this setting, these patien ts could be subjects for cognitive or pharmacologic intervention to delay d isease onset. We have thus followed a cohort of cognitively normal elderly subjects with a Clinical Dementia Rating (CDR) of 0 at autopsy. Thirty-one brains were examined at postmortem according to Consortium to Establish a R egistry for Alzheimer Disease (CERAD) criteria and staged according to Braa k. Ten patients were pathologically normal according to CERAD criteria (la) . Two of these patients were Braak Stage II. Seven very elderly subjects ex hibited a few primitive neuritic plaques in the cortex and thus represented CERAD Ib. These individuals ranged in age from 85 to 105 years and were th us older than the CERAD la group that ranged in age from 72 to 93. Fourteen patients displayed Possible AD according to CERAD with ages ranging from 6 6 to 95. Three of these were Braak Stage I, 4 were Braak Stage II, and 7 we re Braak Stage III. The Apolipoprotein E4 allele was over-represented in th is possible AD group. Neuropsychological data were available on 12 individu als. In these 12 individuals, Possible AD at autopsy could be predicted by cognitive deficits in 1 or more areas including savings scores on memory te sting and overall performance on some measures of frontal executive functio n.