Image of brain with jigsaw piece missing to illustrate memory loss in Alzheimer's disease and dementia
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Results from a large genetic association study show individuals with a genetic propensity to high systolic blood pressure and high-density lipoprotein (HDL) cholesterol are at increased risk for developing Alzheimer’s disease.

As both of these risk factors are potentially modifiable, the authors of the paper describing the research published in JAMA Network Open suggest these results could “inspire new drug targeting and improved early dementia prevention.”

Alzheimer’s disease is the most common form of dementia, impacting an estimated 6.7 million Americans aged 65 or older. A report published in 2020 estimated that 12 modifiable risk factors could prevent or delay up to 40% of dementia cases, but there is some inconsistency in results from clinical trials and observational studies that makes it difficult to make effective evidence-based recommendations for patients or those at risk for dementia.

“Effective interventions should target ameliorating risk factors that lie in the causal pathways. Hence, thoroughly unfolding the genomic background for associations between modifiable risk factors and dementia might help to develop future efficacious preventive and therapeutic approaches,” write the authors.

This study included data from the European Alzheimer & Dementia Biobank from 39,106 people with clinically diagnosed Alzheimer’s disease (aged 72–83 years) and 401,577 individuals without the condition (aged 51–80 years).

After correcting for potential confounding factors, the results showed that genetically linked high systolic blood pressure increased risk for Alzheimer’s by 23% per 10 mmHg increase in blood pressure compared with those without this trait. Similarly, a one standard deviation increase in HDL cholesterol increased the risk of Alzheimer’s by eight percent compared to those without inherited high HDL levels.

“There was no consistent evidence supporting genetic associations of other lipid traits, body mass index, alcohol consumption, smoking initiation, or diabetes with odds of Alzheimer’s disease,” write the authors.

The connection with blood pressure has been suggested in other studies, but “to our knowledge, our study is the first to identify an association between high HDL cholesterol concentrations and higher Alzheimer’s disease risk in a comprehensive range of complementary analyses,” add the investigators.

The researchers concede that a limitation of their study is that individuals included in the study were mostly of White, European ancestry, which may mean these results are not valid in other population groups.

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