Older Adults Taking AT1-Receptor Blockers Exhibit Reduced Cerebral Amyloid Retention

Background: Evidence suggests that angiotensin II AT(1)-receptor blockers (ARBs) may be protective against dementia, and studies in transgenic animals indicate that this may be due to improved amyloid-beta (A beta) clearance. Objective: We investigated whether taking ARBs was associated with an attenuation of age-related increases in cerebral A beta retention, and reduced progression to dementia. Methods: Eight hundred seventy-one stroke-free and dementia-free older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study underwent baseline lumbar puncture, and a subgroup (n = 124) underwent 12 and 24 month follow-up lumbar puncture. Participants were followed at variable intervals for clinical progression to dementia. Linear mixed models and ANCOVA compared ARBs users with those taking other antihypertensives (O-antiHTN) or no antihypertensives (No-antiHTN) on cerebrospinal fluid (CSF) A beta and phosphorylated tau (P-tau) levels. Cox regression and chi-square analyses compared groups on progression to dementia. Results: ARBs users exhibited greater vascular risk and lower educational attainment than the No-antiHTN group. Longitudinal analyses indicated higher CSF A beta and lower P-tau in ARBs users versus other groups. Cross-sectional analyses revealed agerelated decreases in CSF A beta in other groups but not ARBs users. ARBs users were less likely to progress to dementia and showed reduced rate of progression relative to the No-antiHTN group. Discussion: Patients taking ARBs showed an attenuation of age-related decreases in CSF A beta, a finding that is consistent with studies done in transgenic animals. These findings may partly explain why ARBs users show reduced progression to dementia despite their lower educational attainment and greater vascular risk burden.