Neuropathology in a diverse cohort of oldest-old: The LifeAfter90 study

INTRODUCTION: Studies of the oldest-old show great neuropathologic heterogeneity; little is known in diverse populations after age 90. METHODS: LifeAfter90 is a lifecourse cohort study of individuals aged ≥ 90 years evaluated every 6 months with optional brain donation; this study presents initial neuropathological findings. RESULTS: A total of 124 decedents (mean age 96, 49.2% White, 12.1% Black, 16.9% Asian, 18.5% Latino individuals) came to autopsy. At last evaluation, 35% had dementia, 23% cognitive impairment, and 41% normal cognition. 35.5% had intermediate AD, 8.1% had high AD neuropathologic changes, 73% had moderate/severe arteriolosclerosis, 23% one or more microinfarcts, 32% Lewy bodies, 24% TDP-43 deposits, and 4% hippocampal sclerosis. There was a high degree of mixed neuropathology, with 69% having three or more pathologies. Cognitive impairment was most strongly associated with AD pathology. DISCUSSION: Multiple pathologies were common, and many individuals maintained normal cognition indicating substantial neuropathologic burden may be present in the absence of overt cognitive impairment, especially in the oldest-old.