Effect of the angiotensin I-converting enzyme I/D polymorphism on cognitive decline

Several clinical, epidemiological, and pathological observations suggest th at vascular risk factors are associated with cognitive performances. The re nin-angiotensin system components, major determinants of the cardiovascular system, are expressed in the brain. To estimate their potential impact on cognitive performances, we studied the association between cognitive functi oning and an insertion/deletion (I/D) polymorphism of the angiotensin I-con verting enzyme (ACE) gene. In a sample of 1168 highly performing subjects ( 59-71 years), DD homozygotes had the lowest cognitive scores as evaluated b y the Mini-Mental State Examination. Cognitive decline at 4-year follow-up (defined as the loss of at least 3 paints in Mini-Mental State Examination score) was more prevalent in these subjects, the odds ratio being equal to 1.53 (95% CI: 1.04-2.24) with subjects ID as reference class. Moreover, the combined effect of the presence of at least one APOE epsilon 4 allele anti ACE nn homozygosity was a risk factor for cognitive decline. This report r einforces the hypothesis of an influence of cardiovascular risk factors on cognitive performances. (C) 2000 Elsevier Science Inc. All rights reserved.