S5-01-05: Pathological correlates of dementia in a large population-based cohort

Abstract

Conventional views of the pathological substrates of cognitive decline are challenged by the findings of population–based cohorts. Disorders conforming to ‘pure’ consensus guidelines are infrequent and mixed pathologies predominate. Characterization of pathologies underlying cognitive decline in the first 456 deaths within the MRC Cognitive Function and Ageing Study. Comprehensive data on degenerative and vascular pathologies will be analyzed in relationship to cognitive status, genetic risk factors and self–reported risk factors. Prospective longitudinal assessment of respondents in a population–based cohort linked to a brain donation program. Conventional neuropathology was supplemented by post–mortem brain imaging and genetic analyses. Data from the first 209 brains within the study showed that the burden of brain pathology is linked to cognitive decline but does not permit the definition of thresholds for any specific brain lesion (e.g. Alzheimer's pathology, synucleinopathy etc). Mixed pathologies including vascular brain disease were the most frequent finding. Prediction of cognitive status from a global assessment of significant pathological variables is accurate in 4 out of 5 cases. Incorrect predictions include both demented individuals with low pathology burden and cognitively intact individuals with high pathology burden. The findings will be updated based on analysis of data collected from 456 brains up to July 2005. The implications for understanding the interaction of pathology and brain function will be addressed.