People who carry a higher number of genetic variants for increased pulse pressure may be at increased risk of having dementia as a contributing factor in their deaths, research suggests.
The findings, in Neurology, point to shared genetics underpinning cardiometabolic disease and dementia.
Although it is known that cardiometabolic conditions such as high blood pressure, diabetes, and stroke are associated with the neurodegenerative disease, it has been unclear how genetic predictors for the former influence the latter.
Pulse pressure is the difference between systolic and diastolic pressure and a higher number is indicative of poorer cardiac health, such as hardened arteries or poor heart function.
“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,” explained researcher Laura Raffield, PhD, from the University of North Carolina at Chapel Hill.
“Our study found an association with genetic variants linked to high pulse pressure and an increased risk of death from dementia.”
Late-life dementia is strongly inherited, with genetics responsible for around 60% to 80% of Alzheimer’s disease.
While the APOE ɛ4 allele is a well-known genetic risk factor for Alzheimer’s disease, other common genetic variants have been implicated and there may also be vascular contributions.
The study investigated how polygenic risk scores for cardiometabolic disease related to dementia-related outcomes among more than 8000 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
The authors note that REGARDS has particularly high numbers of Black participants, who are underrepresented in late-life dementia research, and eight in 10 in the current study identified as non-Hispanic Black.
Study participants had a mean age of 63.7 years at the start of the study and underwent screening for cognitive function annually. They were followed for up to 14 years for risk of death from dementia and nine years for cognitive impairment, on average.
A total of 619 people developed cognitive impairment during this time compared with 7159 with no such impairment. The 459 individuals who had dementia listed as a cause of death were compared with 8362 who died from other causes or for whom the reason was missing.
A higher polygenic risk score for pulse pressure was associated with a 16% increased risk of dementia as a contributing cause of death, after accounting for potential confounding factors.
This statistically significant result was not seen in polygenic risk scores for systolic or diastolic blood pressure, potentially supporting earlier research indicating that pulse pressure is a better predictor of coronary heart disease.
The polygenic risk score for pulse pressure was not associated with incident cognitive impairment, suggesting limited shared genetics between this dementia-related outcomes.
Overall, there were significant or nominal associations in polygenic risk scores for triglycerides, pulse pressure, type 2 diabetes and both the endpoint of Alzheimer’s disease and related dementias and also dementia as a contributing cause of death. However, this was not the case with incident cognitive impairment.
In addition, the results confirmed that the APOE variant was a predictor of both dementia as a contributing cause of death and incident cognitive impairment, and that local African ancestry was associated with nominally attenuated effect size.
The authors concluded that the inconsistent results between incident cognitive impairment and dementia as a contributing cause of death “imply that different dementia-related end points may capture distinct biological pathways.”
They elaborated: “For example, genetic risk factors of [cardiometabolic diseases] may be more strongly related to later disease progression, such as amyloid accumulation throughout later life, rather than to early cognitive impairment.”
The post Genetically Raised Pulse Pressure Predisposes to Dementia-Linked Death appeared first on Inside Precision Medicine.