Postmortem neurodegenerative markers and trajectories of decline in cognitive systems

Objective: To assess whether neurodegenerative pathologies are differentially related to trajectories of change in different cognitive abilities. Methods: At annual intervals for up to 21 years, 915 older participants in a longitudinal clinical-pathologic cohort study completed a battery of 15 tests from which previously established composite measures of episodic memory, semantic memory, working memory, and perceptual speed were derived. At death, they underwent a neuropathologic examination to quantify Alzheimer’s disease (AD) pathology, Lewy bodies, transactive response DNA-binding protein 43 (TDP-43) pathology, and hippocampal sclerosis plus multiple markers of cerebrovascular disease. Time-varying effect models were used to assess change over time in the relation of neuropathologic markers to cognitive trajectories. Results: Controlling for pathology, decline in perceptual speed was evident about 15 years before death; modest decline in semantic and working memory occurred l...