Risk factors for Alzheimer?s disease and Alzheimer?s disease related dementias include common, age- associated conditions like inflammation, metabolic disorders, atherosclerosis, and cardiovascular disease. A new potential pathway to Alzheimer?s disease and Alzheimer?s disease related dementia?clonal hematopoiesis of indeterminate potential (CHIP)?is also associated with these conditions. CHIP is characterized by the somatic mutation and expansion of hematopoietic stem cell clones into circulating subpopulations of genetically distinct peripheral blood leukocytes. In the project supplement described herein, we propose to leverage data from the Women?s Health Initiative Memory Study (WHIMS) that collectively include over 25 years of cognitive surveillance, with brain MRI data available on a subsample of the WHIMS cohort. The proposed supplement will expand the CHIP sample to include women from WHIMS and WHIMS- ECHO, the ongoing extension of the WHIMS cohort follow-up, allowing for comprehensive examination of cognitive decline and outcomes (adjudicated mild cognitive impairment or probable dementia). Together, the resulting longitudinal phenotypic and somatic genomic data will provide a comprehensive platform for evaluating associations between CHIP onset and progression, cognitive decline, and incident mild cognitive impairment, Alzheimer?s disease, and Alzheimer?s disease related dementias in a large, racially/ethnically diverse group of aging women.
Clonal hematopoiesis of indeterminate potential (CHIP) is a potent risk factor for inflammation, metabolic disorders, atherosclerosis, and cardiovascular disease?all of which are risk factors for cognitive decline, Alzheimer?s disease, and Alzheimer?s disease related dementias. The proposed supplement seeks to expand the sample of an existing study of CHIP in the Women?s Health Initiative to include women with over 25 years of detailed cognitive data (annual cognitive assessments) and brain MRIs to examine the role of CHIP in cognitive function among aging women.
