Renin angiotensin system gene polymorphisms modify angiotensin-converting enzyme inhibitors' effect on cognitive function: The health, aging and body composition study

Ihab Hajjar, Stephen Kritchevsky, Anne B. Newman, Rongling Li, Kristine Yaffe, Eleanor M. Simonsick, Lewis A. Lipsitz

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Objectives: To investigate the effect of polymorphisms in renin angiotensin system genes on the association between angiotensin-converting enzyme inhibitor (ACEI) exposure and global and executive cognitive function in the Health, Aging and Body Composition study. Design: Cohort study. Setting: Community. Participants: Three thousand seventy-five participants: mean age 73.6, 58% Caucasian, 52% female, 15% taking ACE-Is, 8 years of follow-up. Measurements: The outcomes were longitudinal change in Executive Clock Drawing Test-1 (CLOX1), the Digit Symbol Substitution test, and the Modified Mini-Mental State Examination. The genetic polymorphisms included angiotensin-converting enzyme insertion deletion (ACEID) in the ACE gene and the M235T and 6AG polymorphisms in the angiotensinogen (AGT) gene. Results: For the CLOX1 outcome, there was significant interaction between 6AG and M235T polymorphisms in the AGT gene and angiotensin-converting enzyme inhibitors (ACE-Is) in Caucasian participants (P=.01 for both polymorphisms) independent of blood pressure levels. Specifically, ACE-I exposure was protective against CLOX1 score decline in carriers of the AA genotype of the 6AG and the CC genotype of the M235T (for the ACE-I vs non-ACE-I groups, P=.01 for 6AG and P=.005 for M235T) but not the other genotypes. These associations were not significant with other cognitive tests, with ACEID, or in African Americans. Conclusion: ACE-Is may provide a protective effect on executive function in Caucasians with AGT gene polymorphisms known to be associated with greater renin angiotensin system activity. If confirmed in a pharmacogenetic trial, ACE-Is may be found to have additional cognitive protection in a select group of elderly individuals.

Original languageEnglish (US)
Pages (from-to)1035-1042
Number of pages8
JournalJournal of the American Geriatrics Society
Volume58
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Angiotensin- converting enzyme inhibitors
  • Angiotensinogen gene
  • Cognitive function
  • Hypertension

ASJC Scopus subject areas

  • Geriatrics and Gerontology

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