"Preclinical" AD revisited - Neuropathology of cognitively normal older adults

Objective: To classify neuropathologic alterations in the brains of nondeme nted older adults using current sets of criteria for AD. Background: AD neu ropathologic alterations are found in the brains of some nondemented elderl y subjects and suggest the possibility of presymptomatic AD. Three sets of guidelines have been developed to classify AD using senile plaques, neuriti c plaques, and neurofibrillary tangles (NFT), Methods: Neuropathologic chan ges in 59 older adults followed longitudinally with a standard battery of m ental status measures were investigated using Khachaturian, Consortium to E stablish a Registry for Alzheimer's Disease (CERAD), and National Institute on Aging-Reagan Institute (NIA-RI) guidelines. AD neuropathologic markers were evaluated in neocortical and allocortical regions. Cases were categori zed as neuropathologically "normal" or "AD-like" and compared for possible mental status differences. Results: Between 11 and 49% of cases met one or more of the three classifications of AD. With adjustments for multiple comp arisons, only NFT in hippocampal CA1 region were associated with autopsy ag e, suggesting that this may represent a pathologic process associated with normal brain aging. Using the NIA-RI guidelines, subjects in the AD-like gr oup performed less well on the immediate paragraph recall and word-list del ayed recall than their counterparts who did not meet these guidelines. Conc lusions: These data indicate that the prevalence of "preclinical" AD in our population is relatively low based on the NIA-RI classification. Although many subjects had AD-like changes based on CERAD and Khachaturian guideline s, they exhibited no differences in mental performance, suggesting that the aging brain may be able to withstand such structural changes without meani ngful impact on mental functioning.