Synergistic Effects of Aldehyde Dehydrogenase 2 Polymorphisms and Alcohol Consumption on Cognitive Impairment after Ischemic Stroke in Han Chinese

Abstract

Aldehyde dehydrogenase 2 (ALDH2) polymorphisms are related to both stroke risk and alcohol consumption. However, the influence of ALDH2 polymorphisms and alcohol consumption on cognitive impairment after ischemic stroke remains unknown, as do the possible mechanisms. We enrolled 180 Han Chinese ischemic stroke patients from four community health centers in Bengbu, China. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and two different MoCA cutoff scores were used to define cognitive impairment in ischemic stroke patients. The ALDH2 genotypes were determined using polymerase chain reaction and direct sequencing. To assess the associations of ALDH2 polymorphisms and alcohol consumption with cognitive impairment after ischemic stroke, we performed binary logistic regression analysis with odds ratios. We revealed that individuals with the ALDH2 wild-type genotype were more likely to have high MoCA scores than those with the mutant and heterozygous types ( $p=0.034$ ). In addition, using two MoCA cutoff scores, the percentage of moderate to excessive alcohol consumption in the cognitive impairment group was higher than that in the nonimpairment group ( $p=0.001$ ). The levels of 4-hydroxy-2-nonenal ( $p=0.001$ ) and swallowing function ( $p=0.001$ ) were also higher in the cognitive impairment group than in the nonimpairment group. Moreover, after adjusting for other potential risk factors, ALDH2 polymorphisms and alcohol consumption had a significant synergistic effect on cognitive impairment ( $p=0.022$ ). Specifically, the ALDH2 $\ast$ 2 mutant allele and higher alcohol consumption were associated with cognitive impairment and swallowing ability after ischemic stroke. Targeting ALDH2 may be a useful biomarker for cognitive rehabilitation following ischemic stroke.