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Effects of concurrent neuropathologies with Alzheimer disease neuropathologic change on cognitive decline: Minimal impact of vascular brain injury compared with other combinations.

Effects of concurrent neuropathologies with Alzheimer disease neuropathologic change on cognitive decline: Minimal impact of vascular brain injury compared with other combinations.

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Seattle, US · Author affiliation

Department of Epidemiology, National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, United States.
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St. Louis, US · Author affiliation

Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States.
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Original abstract

We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores (trajectories over time for 5 domains: overall cognition, episodic memory, attention, language, executive function). Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC). Using linear mixed-effects models, we examined trajectories of cognitive decline for ADNC alone compared to ADNC plus LBD, VBI, or LATE-NC. We also examined differences between observed trajectories and trajectories that would be expected if the neuropathologic entities exerted their effects independently (additively). ADNC+LBD had worse decline than ADNC alone for 4 of the 5 domains with rate of decline consistent with an additive model for all 4 domains. ADNC+LATE-NC had worse decline than ADNC alone for 3 domains with rate of decline additive for only one and <additive for 2. ADNC+VBI had worse decline than ADNC alone for only one domain, with rate of decline <additive. These findings are relevant for prognostication in clinical practice and for clinical trial design.

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