AMPK γ2 subunit gene PRKAG2 polymorphism associated with cognitive function as well as diabetes in old age

Abstract

Metabolic and cognitive disorders are closely related. However, the mechanism underlying this relationship is still under a debate. AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Energy metabolism deficiency has been consistently implicated in the pathogenesis of cognitive decline such as Alzheimer’s disease as well as metabolic disorders including diabetes. This study aimed to examine whether the AMPK γ2 gene, PRKAG2 -26 C/T polymorphism is associated with cognitive functions and diabetes in the Korean community elderly aged from 60 to 80 (n = 1,609). Multivariate logistic regression analysis showed a significant association between the -26C/T single-nucleotide polymorphism (SNP; CC versus CT/TT) and cognitive impairment (OR, 1.6; 95% CI, 1.1-2.2) after adjusting for age, gender, education, smoking, alcohol drinking, depression, waist circumference and the number of APOE e4 allele. Moreover, this SNP (CC/CT versus TT) was also related to the presence of diabetes (OR, 1.8; 95% CI, 1.2-2.8). Importantly, the relationship between the SNP and cognitive impairment was still significant in persons who had no diabetes (P = 0.015). Further analyses with subpopulation (n = 546) revealed that CC homozygotes relative to T-allele carriers had significantly better performances in verbal and visual memory and attention. These findings collectively supports a hypothesis that AMPK has a role in cognitive functioning, as well as metabolic functioning, in humans even when excluding the potential secondary effect of diabetes on cognition. Further longitudinal study with larger sample size and additional SNPs is warranted.