Cardiometabolic Genetics Linked to Cognitive-Related Outcomes

FRIDAY, June 5, 2026 (HealthDay News) — A higher polygenic risk score (PRS) for pulse pressure is associated with an increased risk for dementia as a contributing cause of death (DCCD), according to a study published online June 3 in Neurology.

Daeeun Kim, Ph.D., from the University of North Carolina at Chapel Hill, and colleagues examined the associations of PRSs for major cardiometabolic diseases (CMDs) and the established APOE risk alleles with dementia-related outcomes in the Reasons for Geographic and Racial Differences in Stroke study. PRSs were constructed for Alzheimer disease and related dementias (ADRDs) and CMDs, including stroke, coronary artery disease, venous thromboembolism, type 2 diabetes, atrial fibrillation, blood pressure, and circulating lipid levels. The predictive performance of each PRS was assessed on their primary end point, and the associations with incident cognitive impairment (ICI) and DCCD were tested.

Up to 8,818 participants were analyzed (83.3 percent Black). The researchers identified a significant association between PRS for pulse pressure and DCCD for CMD PRS (hazard ratio, 1.16; 95 percent confidence interval, 1.06 to 1.28). There was a nominal association seen for the PRS for ADRD with DCCD (hazard ratio, 1.12; 95 percent confidence interval, 1.00 to 1.25), but not with ICI. Among those with African ancestry at the APOE locus, a nominally significant attenuated effect was seen for APOE risk alleles on ICI.

“Our results for pulse pressure suggest there may be shared genetic underpinnings between cardiometabolic diseases and dementia, but more research is needed,” coauthor Laura M. Raffield, Ph.D., also from the University of North Carolina at Chapel Hill, said in a statement.

Abstract/Full Text (subscription or payment may be required)