Multimodal contributions to dementia risk Lead Investigator: Rahul Desikan Institution : UCSF E-Mail : rahuldesikan@gmail.com Proposal ID : 982 Proposal Description: There is increasing consensus that genetics influence dementia risk. Although numerous genome wide association studies have identified numerous genetic variants associated with numerous neurodegenerative diseases, how susceptibility loci impact disease risk is poorly understood. In this proposal, across a number of neurodegenerative diseases, we will evaluate whether genetic and environmental/lifestyle variables interact to influence cognitive decline, and in vivo (CSF, MRI) and post-mortem (neuropathology) measures of neurodegeneration. Our findings will provide novel insights into neurodegenerative diseases and potentially identify therapeutic targets. We will test the hypothesis that genetic markers act synergistically with environmental/lifestyle variables to influence neurodegeneration. Our specific aims are: 1) Evaluate whether genetic variants are associated with cognitive decline, MRI measures of brain atrophy, CSF and neuropathology measures of amyloid and tau. 2) Evaluate whether environmental and clinical measures are associated with cognitive decline, MRI measures of brain atrophy, CSF and neuropathology measures of amyloid and tau. 3) Evaluate whether statistical interactions between genetic variants and environmental measures are associated with cognitive decline, MRI measures of brain atrophy, CSF and neuropathology measures of amyloid and tau.