Key result
ACE-I exposure protected against executive function decline in Caucasian carriers of the AGT gene 6AG AA genotype (P=0.01) and M235T CC genotype (P=0.005) compared to non-users.
Why the study?
Does ACEI exposure improve cognitive function in older adults with specific renin-angiotensin system gene polymorphisms?
Cohort (n=3,075)
Does ACEI exposure improve cognitive function in older adults with specific renin-angiotensin system gene polymorphisms?
ACE inhibitors may offer targeted protection against executive cognitive decline in older Caucasian adults with specific angiotensinogen gene polymorphisms.
ACE-I use may protect executive function in older Caucasian AGT carriers; leaves open need for randomized confirmation before practice change.
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.
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Hajjar et al. (2010) conducted a cohort in Cognitive decline (n=3,075). Angiotensin-converting enzyme inhibitor (ACEI) exposure vs. Non-ACE-I exposure was evaluated on Longitudinal change in Executive Clock Drawing Test-1 (CLOX1), Digit Symbol Substitution test, and Modified Mini-Mental State Examination (p=0.01 for 6AG and 0.005 for M235T). ACE-I exposure protected against executive function decline in Caucasian carriers of the AGT gene 6AG AA genotype (P=0.01) and M235T CC genotype (P=0.005) compared to non-users.
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