Genetic architecture of memory and executive functioning in Alzheimer's disease Glymour Subcontract with University of Washington. PI: Paul Crane Reference: Grant number 1A01AG042437-01A1
Location(s): United States
Ten to 25% of people with late-onset Alzheimer's disease (AD) present with prominent executive deficits. Names such as frontal variant AD, executive prominent AD, and dysexecutive AD have been applied to this phenomenon. Little is known about traditional or genetic risk factors for dysexecutive AD. The overarching goal of this project is to further our understanding of the genetic architecture and clinical epidemiology of dysexecutive AD in the hopes of ultimately developing disease- modifying treatments. This project will leverage large-scale genome-wide genotype and sequence data and cognitive data collected on >17,000 participants across 19 collaborating studies. The investigators will use modern psychometric methods to co-calibrate cognitive data to develop scores on the same metric for memory and executive functioning. The investigators will use these scores to determine a continuous dysexecutive spectrum phenotype they have found to be highly heritable, with a pattern of heritability entirely distinct from that of AD.