title: Older Adults Taking AT1-Receptor Blockers Exhibit Reduced Cerebral Amyloid Retention.
abstract: BACKGROUND
  Evidence suggests that angiotensin II AT1-receptor blockers (ARBs) may be protective against dementia, and studies in transgenic animals indicate that this may be due to improved amyloid-β (Aβ) clearance.
  
  
  OBJECTIVE
  We investigated whether taking ARBs was associated with an attenuation of age-related increases in cerebral Aβ 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) Aβ 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 Aβ and lower P-tau in ARBs users versus other groups. Cross-sectional analyses revealed age-related decreases in CSF Aβ 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.
  
  
  CONCLUSIONS
  Patients taking ARBs showed an attenuation of age-related decreases in CSF Aβ, 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.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nation
authors.forename: Jean
authors.initials: J
authors.lastname: Ho
authors.forename: Belinda
authors.initials: B
authors.lastname: Yew
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid / Q000187:drug effects*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: AT1-receptor blockers; Amyloid-β; CSF biomarkers; antihypertensive medications; blood pressure; tau