Hypertension is an established risk factor for cognitive decline and dementia in older adults, and previous research has suggested possible salutary effects of blood pressure lowering treatments on cognition and neuropathology. Several studies have specifically highlighted renin-angiotensin system drugs, including AT1-receptor blockers and angiotensin-converting-enzyme inhibitors, as potentially benefiting cognition in later life. Nevertheless, pharmacokinetic properties are typically not considered in existing studies or routine clinical practice. To close this gap, a large meta-analysis was published in the September issue of Hypertension, evaluating the potential cognitive benefits of blood-brain barrier (BBB) crossing renin-angiotensin system drugs relative to their nonpenetrant counterparts.
The meta-analysis included randomized clinical trials, prospective cohort studies, and retrospective observational studies. As a result, longitudinal participant data from 14 cohorts from 6 countries (Australia, Canada, Germany, Ireland, Japan, United States) were harmonized, for a total of 12 849 individuals at baseline. Cognition was assessed via the following seven domains: executive function, attention, verbal memory learning, language, mental status, recall, and processing speed.
At 3 years of follow-up, cognitively normal older adults taking blood-brain barrier-crossing renin-angiotensin drugs exhibited better memory recall, relative to those taking nonpenetrant medications (P = .03). This finding was particularly noteworthy, as the BBB-crossing group had relatively higher vascular risk burden and lower mean education level. Still, not all the findings favored BBB-crossing agents, individuals in the BBB-crossing group had relatively inferior attention ability. The other cognitive measures were not significantly different between groups. The authors suggest that these findings may result from some direct neuronal effect on learning memory systems and may be independent of blood pressure.
Reference: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.121.17049
