Abstract Body: Background: High blood pressure (BP) is associated with higher dementia or cognitive impairment risk in observational studies. Prior clinical trial meta-analyses suggested BP-lowering reduces dementia or cognitive impairment risk but evidence for prevention of clinically-ascertained dementia was not definitive.

Methods: PubMed was searched for randomized controlled BP-lowering trials reporting a clinical dementia outcome published from database inception through May 9, 2025. Search terms replicated those of a 2020 meta-analysis but added pragmatic trials comparing more intensive BP-lowering with usual care. Two investigators independently screened articles; trials enrolling >1000 hypertensive participants without baseline cognitive impairment and comparing greater BP-lowering using antihypertensive agents with “control” (placebo, active control, or usual care) were extracted. Primary outcome was new dementia diagnosis independently ascertained by study clinicians. Trials only reporting change in cognitive score without clinical dementia diagnostic assessment were excluded. Publication bias was assessed via funnel plot.

Results: Systematic literature search identified 2742 BP-lowering studies; 13 defined clinically-ascertained dementia as an outcome. Of these, three were excluded for only reporting a composite dementia or cognitive impairment outcome and ten were included in the meta-analysis. Among 91,659 unique participants and over a median 3.95 years follow-up, 1713 dementia events occurred in 46,319 individuals in treatment arms and 1860 events in 45,340 individuals in comparator arms. Greater BP-lowering treatment in intervention arms led to a relative risk of dementia of 0.90 compared with control (95% CI 0.83-0.97; Figure). There did not appear to be publication bias.

Conclusion: Greater BP-lowering in hypertensive patients reduces clinically-ascertained dementia risk. These findings reinforce 2025 ACC/AHA guidelines recommending hypertension treatment to reduce risk of cognitive decline and dementia in addition to the known cardiovascular disease risk reduction benefits.