Alzheimer disease pathology and longitudinal cognitive performance in the oldest-old with no dementia

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Abstract
Objective: It has been hypothesized that individuals without dementia with Alzheimer disease (AD) neuropathology may be in the preclinical stages of dementia and could be experiencing subtle cognitive decline. The purpose of this study was to compare longitudinal cognitive performance in oldest-old individuals without dementia with and without AD neuropathology. Methods: The study included 58 individuals without dementia from The 90+ Autopsy Study, a population-based study of aging and dementia in individuals aged 90 and older. Participants had neurologic and neuropsychological testing every 6 months with an average of 3 years of follow-up. We compared the trajectory of cognitive performance on the Modified Mini-Mental State Examination (3MS) and the California Verbal Learning Test II (CVLT) by level of AD neuropathology. Based on Consortium to Establish a Registry for Alzheimer9s Disease plaque staging, individuals were categorized as having low (none or sparse) or high (moderate or frequent) plaques. Based on Braak and Braak staging, participants were classified as having low (stages I–III) or high (IV–VI) tangles. Results: No significant differences were found in 3MS or CVLT cognitive performance over time based on plaque or tangle staging. Both high and low pathology groups showed modest improvements on the 3MS and CVLT consistent with learning effects. Conclusions: AD neuropathology at autopsy is not associated with the trajectory of cognitive performance in the 3 years before death in oldest-old without dementia. Despite the presence of AD neuropathology at death, oldest-old without dementia display learning effects on cognitive tests. Further research is necessary to understand factors other than AD neuropathology that may affect cognition in the oldest-old.