Alzheimer neuropathologic alterations in aged cognitively normal subjects

The histopathologic changes distinguishing early Alzheimer disease (AD) fro m normal or pathologic aging are not clearly defined. This report describes the autopsy findings of 59 elderly, well-educated, volunteers. They were e xamined longitudinally with mental status testing, some for up to 8 years, as part of our normal aging study. This study reveals that (1) the brains o f many subjects who did not show cognitive impairment on neuropsychologic t esting contain abundant senile plaques (SP) and/or neurofibrillary tangles (NFT); (2) 29 subjects met Khachaturian criteria for AD, 15 met CERAD and 7 met National Institute on Aging-Reagan Institute guidelines; (3) Braak and Braak staging method included 9 in stage IV subjects, 4 in stage V, and 1 in stage VI; (4) there was a progression of NFT from entorhinal cortex to h ippocampus and amygdala as a function of age; (5) 3 subjects met criteria f or a diagnosis of dementia with Lewy bodies but were not demented; (6) cere bral amyloid angiopathy was present in leptomeningeal vessels in 75% of sub jects and in parenchymal vessels in 62% of subjects; (7) only 10 of 59 subj ects (17%) had no or few degenerative brain changes. Our study demonstrates that the brains of a large percentage of cognitively normal, relatively we ll-educated individuals contain numerous degenerative changes and only a sm all percentage are relatively free of these changes.