Abstract
The objective of this work was 2-fold: to generate macrostructural brain signatures of age-related neuropathologies in a community cohort of older adults and to determine the contribution of brain macrostructure to the variation in antemortem cognition after accounting for the contributions of neuropathologies and demographics. Cerebral hemispheres from 165 participants of 2 cohort studies of aging were imaged with magnetic resonance imaging ex vivo (mean age at death = 90 years; standard deviation = 6 years). The volumes of white matter and 42 gray matter regions were measured. The same hemispheres also underwent neuropathologic examination. Alzheimer's disease pathology was negatively associated with volumes of mainly temporal, frontal, and parietal gray matter regions, and with total white matter volume (p < 0.05, false discovery rate-corrected). A negative association was also detected between hippocampal sclerosis and volumes of the hippocampus, as well as other temporal and frontal gray matter regions (p < 0.05, false discovery rate-corrected). The volume of mainly medial temporal lobe regions explained an additional 5%-6% of the variation in antemortem cognition, above and beyond what was explained by neuropathologies and demographics.