ACE I/D polymorphism affects cognitive function and gray-matter volume in amnestic mild cognitive impairment.

To characterize the correlates of cognitive function, serum concentrations of angiotensin converting enzyme (ACE) and brain structure with the ACE insertion or deletion (I/D) polymorphism were analyzed in subjects with amnestic-mild cognitive impairment (aMCI). A group of 48 subjects meeting criteria for aMCI and 36 age-matched control subjects were assessed using a comprehensive battery of standardized neuropsychological tests and magnetic resonance imaging (MRI). The ACE gene's I/D polymorphism was analyzed by means of PCR, and serum ACE concentrations were measured using ultraviolet spectrophotometry. Genotype effects on neuropsychological domains and MRI gray matter volume (GMV) measurements (optimized voxel-based morphometry) were examined using general linear models. The D carriers among the aMCI subjects performed significantly worse on AVLT-delayed recall compared to the I homozygous group. The D carriers had higher serum ACE concentrations than did the I homozygous carriers, though this difference only reached statistical significance in the aMCI group. Compared with the I homozygous carriers, in the aMCI group, D carriers showed smaller GMV of the bilateral middle frontal gyrus, right cuneus, right precentral gyrus, right medial frontal gyrus, right superior frontal gyrus, and left postcentral gyrus. However, there was no significant difference in GMV between I homozygous and D carriers in the normal control group. The study suggests that ACE genotype has considerable effect on the cognitive performance of aMCI subjects, particularly episodic memory, serum activity of ACE, and the structure of specified brain regions. The ACE D allele may be a genetic risk factor for greater atrophy of gray matter in aMCI.