AS690 - Epigenetic Aging Biomarkers of MCI, ADRD, and Brain Aging in the Women’s Health Initiative Memory Study

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Investigator Names and Contact Information

Aladdin Shadyab (ahshadya@health.ucsd.edu)

Introduction/Intent

Age is the strongest risk factor for Alzheimer’s disease and related dementias (ADRD), which disproportionately impact older women. Yet, the age-associated molecular changes underlying ADRD are not well understood. In prior studies, epigenetic age acceleration (EAA), indicating faster biological aging relative to chronological age, was associated with lower cognitive performance and cognitive decline. However, the relationships between EAA and mild cognitive impairment (MCI), ADRD, and brain aging are vastly understudied, especially among older women. We propose to leverage the unique strengths of the racially and ethnically diverse Women’s Health Initiative Memory Study (WHIMS) to address this gap in knowledge. DNA samples from all WHIMS women (N=7,427) will undergo DNA methylation profiling using the Illumina EPIC array at both baseline and the Long Life Study time point 14-18 years later.

Specific Aims:  

Aim 1. Determine the associations of epigenetic age acceleration with: i) incident MCI and ADRD and ii) survival to age 90 without cognitive impairment.

Aim 2. Determine the associations of epigenetic age acceleration with total and regional brain and white matter lesion volumes.

Aim 3. Identify epigenetic signatures associated with cognitive and neuroimaging phenotypes in epigenome-wide association studies.