According to results of a systematic review and meta-analysis, patients with hypertension who took blood-brain barrier (BBB) crossing renin-angiotensin drugs associated with less decline in memory, despite the increased vascular burden, compared with patients who were taking nonpenetrant medications. These findings were published in Hypertension.

Publication databases were searched for studies of hypertension, Alzheimer disease, dementia, and cognition treated with BBB-crossing or nonpenetrative medications. A total of 14 studies (prospective: n=10; retrospective: n=3; randomized trial: n=1) comprising 12,849 patients were included.

At baseline, participants using BBB-crossing medications and nonpenetrant medications did not differ for the cognitive measures of verbal learning memory (g, 0.0007; P =.98), verbal recall memory (g, -0.04; P =.60), processing speed (g, -0.16; P =.48), executive function (g, 0.04; P =.45), attention (g, 0.04; P =.40), mental status (g, -0.05; P =.13), and language (g, 0.02; P =.12).

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After a 3-year follow-up, verbal recall memory was significantly higher among the BBB-crossing cohort (effect size, 0.07; 95% CI, 0.01-0.12; P =.03; I2, 0%) and the nonpenetrant medication users had superior attention scores (effect size, -0.17; 95% CI, -0.23 to -0.10; P =.02; I2, 0%).

Group differences at follow-up were not observed for mental status (g, 0.02; P =.88), executive function (g, -0.03; P =.80), language (g, -0.01; P =.41), or verbal learning memory (g, 0.05; P =.19).

These findings may have been biased by underlying cohort differences such as significant differences of gender (P <.02) and education (P =.02) as well variation in ethnic diversity in differing studies.

These data indicated that the antihypertensive medications taken by many patients decades before the onset of the cognitive decline associated with Alzheimer disease may be affected by long-term use. BBB-crossing renin-angiotensin drugs were associated with less decline in memory but worse attention.

These seemingly contradictory findings may be explained by the increased vascular burden associated with BBB-crossing medications.


Ho JK, Moriarty F, Manly JJ, et al. Blood-brain barrier crossing renin-angiotensin drugs and cognition in the elderly: a meta-analysis. Hypertension. Published online June 21, 2021. 2021;hypertensionaha12117049. doi:10.1161/hypertensionaha.121.17049

This article originally appeared on The Cardiology Advisor