Population‐based analysis of pathological correlates of dementia in the oldest old

OBJECTIVE: The aim of this study was to analyze brain pathologies which cause dementia in the oldest old population. METHODS: All 601 persons aged ≥85 years living in the city of Vantaa (Finland), on April 1st, 1991 formed the study population of the Vantaa85 + study, 300 of whom were autopsied during follow‐up (79.5% females, mean age‐at‐death 92 ± 3.7 years). Alzheimer's disease (AD) pathology (tau and beta‐amyloid [Aβ]), cerebral amyloid angiopathy (CAA) and Lewy‐related pathologies were analyzed. Brain infarcts were categorized by size (<2 mm, 2–15 mm, >15 mm) and by location. Brain hemorrhages were classified as microscopic (<2 mm) and macroscopic. RESULTS: 195/300 (65%) were demented. 194/195 (99%) of the demented had at least one neuropathology. Three independent contributors to dementia were identified: AD‐type tau‐pathology (Braak stage V‐VI), neocortical Lewy‐related pathology, and cortical anterior 2–15 mm infarcts. These were found in 34%, 21%, and 21% of the demented, respectively, with the multivariate odds ratios (OR) for dementia 5.5, 4.5, and 3.4. Factor analysis investigating the relationships between different pathologies identified three separate factors: (1) AD‐spectrum, which included neurofibrillary tau, Aβ plaque, and neocortical Lewy‐related pathologies and CAA (2) >2 mm cortical and subcortical infarcts, and (3) <2 mm cortical microinfarcts and microhemorrhages. Multipathology was common and increased the risk of dementia significantly. INTERPRETATION: These results indicate that AD‐type neurodegenerative processes play the most prominent role in twilight cognitive decline. The high prevalence of both neurodegenerative and vascular pathologies indicates that multiple preventive and therapeutic approaches are needed to protect the brains of the oldest old.