Developing a DNAm Biomarker for Cognitive Aging: Addressing Disparities and Promoting Community Engagement

The proposed study aims to investigate cognitive aging and cognitive health differences across racial and ethnic groups, with a focus on the role of DNA methylation (DNAm) patterns associated with cognitive performance in later life. This research addresses the public health challenge posed by higher rates of cognitive impairment and dementia observed in African Americans, Hispanics/Latinos, and Native Americans compared to non-Hispanic Whites. The study hypothesizes that socioeconomic factors (SES), such as education and occupation, are associated with DNAm patterns linked to cognitive health.
The study design involves a retrospective analysis of data from the Health and Retirement Study (HRS) with linked DNAm data. The analysis plan prioritizes cross-sectional cognitive phenotypes, with longitudinal data incorporated where available. Using elastic net linear regression, we will develop DNAm-based biomarkers of general cognitive ability and domain-specific cognitive performance. We will examine associations between SES indicators and DNAm cognitive scores and explore whether DNAm patterns statistically account for group differences in cognitive outcomes, with race/ethnicity evaluated as a secondary and exploratory factor.
Longitudinal analyses are planned to evaluate whether DNAm cognitive scores are associated with subsequent cognitive change and risk of cognitive impairment, using mixed-effects modeling approaches, subject to data availability and statistical power.
In addition to quantitative analyses, the study includes a qualitative questionnaire component developed separately to assess community knowledge, perceived barriers, and attitudes toward epigenetic biomarkers and dementia risk among older adults from diverse backgrounds. Data from this survey are investigator-collected and analyzed independently from NIAGADS DSS data.
This study aligns with NIAGADS’s mission by leveraging genomic and epigenomic data to advance understanding of cognitive aging and by generating DNAm-derived cognitive measures that can support future mechanistic and translational research.

Our research seeks to understand how biological changes measured in blood relate to cognitive health in older adults. We are studying whether differences in life experiences such as education and other socioeconomic factors are reflected in patterns of DNA methylation and whether these patterns are associated with cognitive performance later in life.
Using data from large, long-running studies of aging, we aim to develop a blood-based measure of cognitive functioning based on DNA methylation. This measure may help identify individuals at higher risk for cognitive impairment and improve understanding of how cognitive health varies across individuals and groups.
We are also developing a separate survey to better understand how older adults from diverse backgrounds perceive dementia risk and emerging biological markers. By combining biological research with community perspectives, our goal is to ensure that advances in cognitive aging research are relevant, understandable, and useful for a broad range of communities.