Impact of Renin-Angiotensin-Aldosterone System Modulation on Cognitive and Neuropsychiatric Outcomes: A Systematic Review of Clinical and Mechanistic Evidence.

This systematic review explores the influence of the renin-angiotensin-aldosterone system (RAAS) on cognitive and neuropsychiatric outcomes, synthesizing evidence from clinical and preclinical studies investigating RAAS-modulating therapies such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). A comprehensive literature search across four major databases yielded seven studies that met the inclusion criteria, including randomized controlled trials, observational studies, and one animal model experiment. The findings suggest that RAAS modulation, particularly through ARBs, may offer cognitive benefits in certain populations, especially those with hypertension, type 2 diabetes, or vascular risk factors. Some studies demonstrated improvements in executive function, memory, and global cognition, while others found no statistically significant effect on neurodegeneration or cognitive decline. Mechanistic insights indicate that RAAS-targeting interventions may reduce neuroinflammation, oxidative stress, and microvascular dysfunction, which are pathways implicated in cognitive impairment. Although promising, the evidence is varied in methodological quality and consistency, highlighting the need for future trials with cognitive endpoints as primary outcomes.