ArticleNeurology2023
Polygenic Susceptibility to Hypertension and Cognitive Performance in Middle-aged Persons Without Stroke or Dementia.
Article in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Blood pressure polygenic score, cardiorespiratory fitness and odds of dementia: the HUNT Study.Age and ageing · 2026Article
- Multiomics Profiling Supports Cathepsin B as a Protective Factor in Cerebral Small Vessel Disease.Research square · 2026Article
- Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.Annals of neurology · 2025Article
- Association of Cardiovascular-Kidney-Metabolic Syndrome With Cognitive Decline and Dementia: The ARIC Study Insights.Journal of the American Heart Association · 2025Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
objectivesMounting evidence indicates that hypertension leads to a higher risk of dementia. Hypertension is a highly heritable trait, and a higher polygenic susceptibility to hypertension (PSH) is known to associate with a higher risk of dementia. We tested the hypothesis that a higher PSH leads to worse cognitive performance in middle-aged persons without dementia. Confirming this hypothesis would support follow-up research focused on using hypertension-related genomic information to risk-stratify middle-aged adults before hypertension develops.
methodsWe conducted a nested cross-sectional genetic study within the UK Biobank (UKB). Study participants with a history of dementia or stroke were excluded. We categorized participants as having low (≤20th percentile), intermediate, or high (≥80th percentile) PSH according to results of 2 polygenic risk scores for systolic and diastolic blood pressure (BP) generated with data on 732 genetic risk variants. A general cognitive ability score was calculated as the first component of an analysis that included the results of 5 cognitive tests. Primary analyses focused on Europeans, and secondary analyses included all race/ethnic groups.
resultsOf the 502,422 participants enrolled in the UKB, 48,118 (9.6%) completed the cognitive evaluation, including 42,011 (8.4%) of European ancestry. Multivariable regression models using systolic BP-related genetic variants indicated that compared with study participants with a low PSH, those with intermediate and high PSH had reductions of 3.9% (β -0.039, SE 0.012) and 6.6% (β -0.066, SE 0.014), respectively, in their general cognitive ability score ( DISCUSSION: Among nondemented, community-dwelling, middle-aged Britons, a higher PSH is associated with worse cognitive performance. These findings suggest that genetic predisposition to hypertension influences brain health in persons who have not yet developed dementia. Because information on genetic risk variants for elevated BP is available long before the development of hypertension, these results lay the foundation for further research focused on using genomic data for the early identification of high-risk middle-aged adults.
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