Integration of genetic risk, cardiometabolic diseases, and cognitive impairment among African American adults
Year: 2025
Type: article
Abstract: BACKGROUND: African American (AA) adults have a high burden of late-life cognitive impairment (CI) and dementia but remain underrepresented in genetic epidemiology studies. Genetic risk and cardiometabolic diseases (CMDs) contribute to dementia risk. This study investigated whether genetic susceptibility and CMDs were associated with a composite CI outcome and whether CMDs modified these associations. METHODS: In AA participants within the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we assessed the association of a dementia polygenic risk score (PRS), APOE ε4 carrier status, and three prevalent CMDs: stroke, coronary artery disease (CAD), and type 2 diabetes (T2D) with a composite outcome of CI and dementia as a contributing cause of death (DCCD). We used logistic regression adjusted for age, sex, education, income, body mass index, smoking status, alcohol intake, physical activity, hypertension, low-density lipoprotein, and C-reactive protein. Interaction terms were included to assess whether CMDs modified the associations between genetic risk and the composite outcome. RESULTS: Of 8,838 participants, 516 (5.84 %) developed CI or had DCCD. In fully adjusted models, high polygenic risk (highest vs lowest PRS tertile) was associated with increased odds of the composite outcome [odds ratio (OR): 1.42; 95 % confidence interval (CI): 1.12-1.78], as was APOE ε4 carrier status (OR: 1.46; 95% CI: 1.21-1.78). Among CMDs, stroke (OR: 1.45; 95% CI: 1.04-2.02) and T2D (OR: 1.31; 95% CI: 1.06-1.61) were significantly associated with increased odds of the composite outcome. However, the association between genetic risk and the composite outcome did not significantly differ by CMD status. CONCLUSION: Genetic risk and CMDs independently contributed to dementia-related outcomes, indicating their relevance in understanding dementia risk among AA adults.
Authors: Chaitali Dagli, Nicole D. Armstrong, Daeeun Kim, Laura M. Raffield, Hemant K. Tiwari, Mary Cushman, Suzanne E. Judd, Michael Crowe, Virginia J. Howard, Marguerite R. Irvin
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,170
Awards: VCID and Stroke in a Bi-racial National Cohort, G1459159051, G1671748052, G2784128823, G4963625512, G6400280860, G744069829, G7771549977, Immune Cells in Alzheimer’s Disease and Related Dementias in the Jackson Heart Study, G893051965, G9000008877, G9000093456, G9000187329, Shared and novel contributors to risk of stroke and stroke recurrence in a multiethnic population – the role of social determinants of health, genetics, and epigenetics, Proteomic biomarkers of incident cognitive impairment in Black and White adults, G939786002
OpenAlex ID: W4417537443