Higher genetic pulse pressure risk associated with dementia-related mortality

When looking at genetic variants in a person's DNA that predispose them to disease, a new study has found having a higher number of genetic variants for increased pulse pressure is associated with a small, increased risk of dementia as a contributing cause of death. The study was published June 3, 2026, in Neurology^®, the medical journal of the American Academy of Neurology.

In blood pressure, pulse pressure is the difference between the top number, systolic, and the bottom number, diastolic. It is the force generated by the heart when it contracts, with high pulse pressure indicating poor heart health, including stiffened arteries or poor heart valve function.

While the study found an association, it does not prove that having genetic variants for higher pulse pressure causes dementia-related death.

"Cardiometabolic diseases like high blood pressure, diabetes and stroke are associated with an increased risk of dementia, but it remains unclear whether genetic predictors of these diseases influence that risk," said study author Laura M. Raffield, PhD, of the University of North Carolina at Chapel Hill. "While having the APOE ɛ4 allele, a gene variant, is the strongest common genetic risk factor for Alzheimer's disease, some people may inherit a combination of small effect gene variants linked to cardiometabolic disease that may also increase the risk. Our study found an association with genetic variants linked to high pulse pressure and an increased risk of death from dementia."

For the study, researchers looked at the genetics of 8,818 people who had an average age of 64 at the start of the study and were followed for up to 14 years for risk of death from dementia and 9 years for cognitive impairment on average.

Participants had genotyping, which detects small differences in a person's DNA sequence.

Researchers constructed polygenic risk scores. These scores look at genetic variants in a person's DNA to calculate their predisposition to a disease. They constructed scores for 11 cardiometabolic diseases and cardiometabolic risk factors: systolic blood pressure; diastolic blood pressure; pulse pressure; blood cholesterol (LDL and HDL); triglycerides; venous thromboembolism; atrial fibrillation; coronary artery disease; type 2 diabetes; and stroke. For example, there were 1,289 gene variants for type 2 diabetes and 60 gene variants for stroke. They also constructed a risk score for Alzheimer's disease and related dementias.

Participants took cognitive tests, either a short screening test or a more expanded set of tests, every one to two years. A total of 619 people developed cognitive impairment during the study. For the participants who died during the study, researchers reviewed a U.S. death records database to determine if dementia was listed as a first or contributing cause of death. The 456 participants who had dementia listed were compared to people who were still alive and to those who had a different or a missing cause of death.

Once researchers adjusted for other factors that could affect the risk of dementia as a contributing cause of death, such as age, sex and other genetic factors, they found that having a higher risk score for pulse pressure was associated with a 16% increased risk of dementia as a contributing cause of death. They did not find strong links for other diseases, or associations with genetic risk for those diseases and cognitive impairment, though Raffield noted that statistical power to detect small effects was limited.

"Our results for pulse pressure suggest there may be shared genetic underpinnings between cardiometabolic diseases and dementia, but more research is needed," said Raffield. "Our findings also imply that genetic risk factors for high pulse pressure may be more strongly related to later dementia disease progression rather than to early cognitive impairment."

A limitation of the study was that some cases of dementia as a cause of death may have been missed in the U.S. database.

The study was supported by the National Institutes of Health.