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Approved research

The genetic basis for Alzheimer's and neurodegenerative disease : understanding etiology and interaction with other risk factors.

Principal Investigator: Dr Yann Klimentidis
Approved Research ID: 21259
Approval date: August 15th 2016

Lay summary

The aim of the proposed research is to examine how lifestyle factors such as physical activity may interact with genetic risk factors to increase susceptibility to Alzheimer?s disease (AD) and related measures of cognitive decline such as dementia and mild cognitive impairment. We will also attempt to gain a better understanding of the etiology of AD by examining the genetic overlap of AD with other diseases and traits, such as insulin resistance and cardiovascular biomarkers. The main health conditions under investigation are thus AD and cognitive decline. With an aging population and longer lifespans, AD is becoming a major public health concern. Identifying the genetic and lifestyle factors underlying this disease is an important step towards improved prediction, prevention, and treatment. We will be looking for links among genetic variants, lifestyle factors, family history, biomarkers, AD, and measures of cognitive decline. We will consider all genetic variants that are available, and we will also focus on previously established/known genetic markers. We will look for genetic variants and lifestyle factors that are associated with AD, then examine how the effect of genetic factors is modified by lifestyle factors and vice-versa. We will use standard statistical procedures such as linear and logistic regression, as well as multivariate regression. We would like to use the full cohort.

Scope extension: We request an extension of the scope of this project to include an evolutionary model of gene by lifestyle behavior interactions on brain aging. Recent work suggests that lifestyle factors, including physical activity (PA), may have been a target of natural selection. We would like to extend the scope of our application to include additional analyses focused on determining how natural selection may have acted on PA levels in ways that link behavior and neurodegenerative disease risk. We will use a suite of statistical techniques to examine how evolutionary forces shaped physical activity and how this evolutionary history impacts the association between physical activity and brain aging. This analysis will also focus on the potential for antagonistic pleiotropy in genes associated with physical activity and Alzheimer's disease. A better understanding of the evolutionary forces underlying human lifestyle behaviors will help us develop new targets for precision health focused interventions to reduce risk of developing Alzheimer's disease and related dementias.