title: Alcohol consumption and cognitive impairment in older men: a mendelian randomization study.
abstract: OBJECTIVE
  To determine whether alcohol consumption is causally associated with cognitive impairment in older men as predicted by mendelian randomization.
  
  
  METHODS
  Retrospective analysis of a cohort study of 3,542 community-dwelling men aged 65 to 83 years followed for 6 years. Cognitive impairment was established by a Mini-Mental State Examination score of 23 or less. Participants provided detailed information about their use of alcohol during the preceding year and were classified as abstainers, occasional drinkers, and regular drinkers: mild (<15 drinks/wk), moderate (15-27 drinks/wk), heavy (28-34 drinks/wk), and abusers (≥35 drinks/wk). We genotyped the rs1229984 G→A variant of the alcohol dehydrogenase 1B (ADH1B) gene, which is associated with lower prevalence of alcohol abuse and dependence. Other measures included age, education, marital status, smoking and physical activity, body mass index, diabetes, hypertension, and cardiovascular diseases.
  
  
  RESULTS
  At study entry, rs1229984 G→A polymorphism was associated with lower prevalence of regular use of alcohol and decreased consumption among regular users. Six years later, 502 men (14.2%) showed evidence of cognitive impairment. Abstainers and irregular drinkers had higher odds of cognitive impairment than regular drinkers (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.00-1.51, after adjustment for other measured factors). The rs1229984 G→A polymorphism did not decrease the odds of cognitive impairment (AA/GG OR = 1.35, 95% CI = 0.29-6.27; GA/GG OR = 1.05, 95% CI = 0.71-1.55).
  
  
  CONCLUSIONS
  Alcohol consumption, including heavy regular drinking and abuse, is not a direct cause of cognitive impairment in later life. Our results are consistent with the possibility, but do not prove, that regular moderate drinking decreases the risk of cognitive impairment in older men.
authors.affiliation: From the School of Psychiatry & Clinical Neurosciences (O.P.A.), and School of Medicine and Pharmacology (G.J.H., B.B.Y., L.F.), University of Western Australia, Perth; WA Centre for Health & Ageing (O.P.A., L.F.), Centre for Medical Research, Perth; Departments of Psychiatry (O.P.A.) and Geriatric Medicine (L.F.), Royal Perth Hospital; Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital, Perth; Department of Endocrinology (B.B.Y.), Fremantle Hospital, Fremantle; Queensland Research Centre for Peripheral Vascular Disease (J.G.), School of Medicine and Dentistry, James Cook University, Townsville; and Department of Vascular and Endovascular Surgery (J.G.), The Townsville Hospital, Townsville, Australia.
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology*; D000437:Alcoholism / Q000150:complications* / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D003430:Cross-Sectional Studies; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase