Journal of Alzheimer's Disease · Jun 18, 2026

Association between renin angiotensin system and cognitive outcomes over 15 years: The Look AHEAD study

By Yasar S, Anderson A, Hayden KM et al.

BackgroundEvidence suggests that dysregulation of the renin angiotensin system (RAS) is associated with the pathophysiologic process of Alzheimer's disease (AD). Few studies have evaluated the relationship between circulating RAS components and incident cognitive decline or impairment.ObjectiveOur study aims to evaluate the relationship between circulating RAS biomarkers (angiotensin II [ANGII], angiotensin 1-7 [ANG1-7], angiotensin converting enzyme-1 [ACE-1], and 2 [ACE-2]), in initially cognitively healthy adults, and incident cognitive decline and cognitive impairment.MethodsIn this secondary analysis, 310 community-dwelling participants from the randomized controlled Action for Health in Diabetes (Look AHEAD) study without dementia, who were not on RAS-altering medication, were included.ResultsParticipants, compared to those excluded, were more likely to be female (65%), white (76%), overweight (34%), have lower baseline HbA1c (6.7%), lower SBP (119.7 mmHg), lower serum creatinine (0.79 mg/dL), higher total cholesterol (190.1 mg/dL) and LDL (112.5 mg/dL), and higher history of dyslipidemia (65%) at baseline. 1 SD increase of ANG1-7 measured in year 1 was associated with lower odds of cognitive impairment (OR = 0.35, 95% CI 0.16-0.77; p = 0.001), while higher ANG1-7 levels predicted better global cognitive function [β x 10⁻³ = 1.03 (0.50); p = 0.039], 15 years later.ConclusionsThese results provide preliminary evidence that circulating RAS components are predictive of protection against cognitive impairment and decline and may serve as a marker of the early stages of dementia. Further research is warranted to fully understand the relationship between the brain and the circulatory RAS.

doi.org/10.1177/13872877261458824 Open access PubMed 42312371 Biomarkers