Dataset Information

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.

SUBMITTER: Almeida OP

PROVIDER: S-EPMC3962996 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Alcohol consumption and cognitive impairment in older men: a mendelian randomization study.

Almeida Osvaldo P OP Hankey Graeme J GJ Yeap Bu B BB Golledge Jonathan J Flicker Leon L

Neurology 20140219 12

<h4>Objective</h4>To determine whether alcohol consumption is causally associated with cognitive impairment in older men as predicted by mendelian randomization.<h4>Methods</h4>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 ...[more]

PMID: 24553426

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Project description:Background: Altered lipid metabolism may be a risk factor for dementia, and blood cholesterol level has a strong genetic component. We tested the hypothesis that dyslipidemia (either low levels of high-density lipoprotein cholesterol (HDL-C) or high total cholesterol) is associated with cognitive status and domains, and assessed causality using genetic predisposition to dyslipidemia as an instrumental variable. Methods: Using data from European and African genetic ancestry participants in the Health and Retirement Study, we selected observations at the first non-missing biomarker assessment (waves 2006-2012). Cognition domains were assessed using episodic memory, mental status, and vocabulary tests. Overall cognitive status was categorized in three levels (normal, cognitive impairment non-dementia, dementia). Based on 2018 clinical guidelines, we compared low HDL-C or high total cholesterol to normal levels. Polygenic scores for dyslipidemia were used as instrumental variables in a Mendelian randomization framework. Multivariable logistic regressions and Wald-type ratio estimators were used to examine associations. Results: Among European ancestry participants (n = 8,781), at risk HDL-C levels were associated with higher odds of cognitive impairment (OR = 1.20, 95% CI: 1.03, 1.40) and worse episodic memory, specifically. Using cumulative genetic risk for HDL-C levels as a valid instrumental variable, a significant causal estimate was observed between at risk low HDL-C levels and higher odds of dementia (OR = 2.15, 95% CI: 1.16, 3.99). No significant associations were observed between total cholesterol levels and cognitive status. No significant associations were observed in the African ancestry sample (n = 2,101). Conclusion: Our study demonstrates low blood HDL-C is a potential causal risk factor for impaired cognition during aging in non-Hispanic whites of European ancestry. Dyslipidemia can be modified by changing diets, health behaviors, and therapeutic strategies, which can improve cognitive aging. Studies on low density lipoprotein cholesterol, the timing of cholesterol effects on cognition, and larger studies in non-European ancestries are needed.

Project description:Background: Previous observational studies have provided inconsistent evidence for the association between alcohol consumption and the risk of colorectal cancer (CRC). To assess this potential causal effect, we performed bidirectional Mendelian randomization (MR) analysis. Methods: We selected six single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) associated with alcohol consumption (ever versus never drinker) and two SNPs representing the number of drinks per week from a genome-wide association study (GWAS) of the Japanese population. Summary data for CRC were obtained from a GWAS meta-analysis in the Japanese population of 6,692 CRC cases and 27,178 controls. MR analysis was performed by the inverse-variance weighted (IVW) method primarily, supplemented with several sensitivity methods including the weighted median method, maximum likelihood method, MR pleiotropy residual sum and outlier (MR-PRESSO) test, MR-Egger regression, Causal Analysis Using Summary Effect estimates (CAUSE) method, as well as constrained maximum likelihood and model averaging and Bayesian information criterion (cML-MA-BIC) method. Multivariable Mendelian randomization (MMR) analyses were used to adjust for potential confounders. Reverse MR analyses were also performed to assess the potential causal effect of CRC on alcohol consumption. Results: Genetically predicted alcohol consumption (ever versus never drinker) was positively associated with the risk of CRC (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.05-1.12, p = 1.51 × 10-5 by IVW). The number of alcoholic drinks per week was also associated with an increased risk of CRC (OR = 1.39, 95%CI: 1.27-1.52, p = 5.29 × 10-13 by IVW). Sensitivity analysis yielded similar results. Reverse MR analyses found no evidence that CRC contributes to either ever drinkers (OR = 1.00, 95%CI: 0.99-1.00, p = 0.339 by IVW) or added number of drinks per week (OR = 1.01, 95%CI: 0.98-1.05, p = 0.545 by IVW). Conclusion: Our study suggested a potential causal association between alcohol consumption and the risk of CRC among Asians. Reducing drinking may be beneficial to the prevention and management of CRC.

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Dataset Information

Alcohol consumption and cognitive impairment in older men: a mendelian randomization study.

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Alcohol consumption and cognitive impairment in older men: a mendelian randomization study.

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