Meta-analysis links hypertension to altered brain function on resting-state fMRI

Hypertension is increasingly recognized as a contributor to cognitive decline and altered brain function, with resting-state functional magnetic resonance imaging (rs-fMRI) offering a non-invasive method to assess spontaneous brain activity and connectivity. This study systematically reviewed and quantitatively synthesized rs-fMRI findings in hypertensive individuals compared to normotensive controls, and within hypertensive subgroups (cognitively normal vs. impaired). A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library (January 2014-March 2024) identified 15 studies for qualitative synthesis, with 11 eligible for meta-analysis using random-effects models. Heterogeneity was assessed with the I2 statistic and bias via the Newcastle-Ottawa Scale. Results showed a moderate pooled effect size of d = 0.64 (95% CI: 0.39-0.89, I2 = 22.9%) for brain functional alterations, with consistent involvement of frontal, temporal, precuneus, cerebellar, and default mode network-related regions across individual studies. With larger effects in hypertensive versus normotensive individuals (d = 0.74, I2 = 39.5%), a moderate effect in cognitively impaired versus normal hypertensives (d = 0.56, I2 = 0%, n = 3), and a large effect for seed-based functional connectivity (d = 0.93, I2 = 0%, n = 2). Sensitivity analysis excluding high-effect studies (n = 2) confirmed robustness (d = 0.57, I = 19.7%). A Graphical Display of Study Heterogeneity (GOSH) plot of 1981 subsets, each with three or more studies, showed consistent effect sizes (d ≈ 0.5-0.7) and low-to-moderate heterogeneity (I = 0%-40%), supporting stability. Hypertension is significantly associated with altered brain function, particularly in memory and executive regions, suggesting rs-fMRI as a promising biomarker for early cognitive vulnerability detection.