Neuropathologic substrates for motor and cognitive impairment in three existing cohort studies of Alzheimer's disease and related dementias

抽象/总结

Abstract/Summary The proposed work will investigate the pathogeneses of late life cognitive and motor impairments attributed to Alzheimer's disease, closely allied cerebrovascular and neurodegenerative diseases, brain aging, and their common patterns of co-occurrence in three existing cohorts: the Honolulu-Asia Aging Study, the Nun Study, and the 90+ Study. Our focus will be on relationships among objective, longitudinal measures of motor function and cognition–with the last obtained proximate to death–and a defined set of neuropathologic substrates identified at autopsy. Parallel and merged analyses will be carried out using existing resources provided from these three large population-based longitudinal studies composed of participants with distinctly different gender, age, and ethnicity. We will leverage these substantial existing resources to test the hypothesis that cognitive and motor impairments that occur with advancing age are syndromic and derive from a partially overlapping mix of diseases that vary among individuals in part by age, sex, and ethnicity, and that can be identified best at the current time by their neuropathologic features. This will allow the identification of common patterns for the singular, concurrent, or sequential development of cognitive and/or motor impairments in persons with and without dementia. The informational wealth of these three studies (all established and supported with NIA funding) will be further expanded and available to teams of collaborating researchers for continuing analyses.