title: AMPK γ2 subunit gene PRKAG2 polymorphism associated with cognitive impairment as well as diabetes in old age.
abstract: Metabolic and cognitive disorders are closely related. However, the molecular mechanism underlying this association is still elusive. Given the importance of energy metabolism in neuronal cells, AMP-activated protein kinase (AMPK), a master switch of energy metabolism, could be an independent factor affecting cognitive as well as metabolic functions. Therefore, we examined the relationship between the AMPK γ2 gene, the PRKAG2 -26C/T polymorphism and cognitive impairment or diabetes in 1609 subjects aged from 60 to 80. We performed multivariate logistic regression analyses with adjustment for age, gender, education, smoking, alcohol, depression, waist circumference, APOE e4, and stroke history. We found a significant association between the -26C/T polymorphism (CC vs. CT/TT) and cognitive impairment (OR, 1.6; 95% CI, 1.1-2.3). Moreover, this polymorphism (CC/CT vs. TT) was also related to the presence of diabetes (OR, 1.8; 95% CI, 1.2-2.8). Importantly, the relationship with cognitive impairment was still significant in non-diabetic individuals (OR, 1.6; 95% CI, 1.1-2.4). Further analyses with a subpopulation (n=611) revealed that CC homozygotes relative to T-allele carriers had significantly better performances in verbal memory and attentional tasks. These findings collectively support a hypothesis that AMPK has a role not only in metabolic functioning but also in cognitive functioning in humans. Extended longitudinal study with a larger number of samples is warranted.
authors.affiliation: Department of Psychiatry, Institute of Behavioral Sciences in Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Eosu
authors.initials: E
authors.lastname: Kim
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Kang Soo
authors.initials: KS
authors.lastname: Lee
authors.forename: Hae-Kwan
authors.initials: HK
authors.lastname: Cheong
authors.forename: Kee
authors.initials: K
authors.lastname: Namkoong
authors.forename: Chang Hyung
authors.initials: CH
authors.lastname: Hong
authors.forename: Byoung Hoon
authors.initials: BH
authors.lastname: Oh
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003072:Cognition Disorders / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011597:Psychomotor Performance
chemical_list: C526223:PRKAG2 protein, human; D055372:AMP-Activated Protein Kinases