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Interaction between Alcohol Consumption and Apolipoprotein E (ApoE) Genotype with Cognition in Middle-Aged Men

Published online by Cambridge University Press:  14 July 2020

Riki E. Slayday
Department of Psychology, San Diego State University, San Diego, CA, USA
Daniel E. Gustavson
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Jeremy A. Elman
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Asad Beck
Graduate Program in Neuroscience, University of Washington, Seattle, WA, USA
Linda K. McEvoy
Department of Radiology, University of California San Diego, La Jolla, CA, USA
Xin M. Tu
Department of Family Medicine, University of California San Diego, La Jolla, CA, USA
Bin Fang
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Richard L. Hauger
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA
Michael J. Lyons
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
Ruth E. McKenzie
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
Mark E. Sanderson-Cimino
Department of Psychology, San Diego State University, San Diego, CA, USA Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Hong Xian
Department of Biostatistics, St. Louis University, St. Louis, MO, USA
William S. Kremen
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
Carol E. Franz*
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
**Correspondence and reprint requests to: Carol E. Franz, PhD, Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, MC 0738, La Jolla, CA92093, USA. Tel: +1 858 822 1793. E-mail:



Heavy alcohol consumption is associated with poorer cognitive function in older adults. Although understudied in middle-aged adults, the relationship between alcohol and cognition may also be influenced by genetics such as the apolipoprotein (ApoE) ε4 allele, a risk factor for Alzheimer’s disease. We examined the relationship between alcohol consumption, ApoE genotype, and cognition in middle-aged adults and hypothesized that light and/or moderate drinkers (≤2 drinks per day) would show better cognitive performance than heavy drinkers or non-drinkers. Additionally, we hypothesized that the association between alcohol use and cognitive function would differ by ApoE genotype (ε4+ vs. ε4−).


Participants were 1266 men from the Vietnam Era Twin Study of Aging (VETSA; M age = 56; range 51–60) who completed a neuropsychological battery assessing seven cognitive abilities: general cognitive ability (GCA), episodic memory, processing speed, executive function, abstract reasoning, verbal fluency, and visuospatial ability. Alcohol consumption was categorized into five groups: never, former, light, moderate, and heavy.


In fully adjusted models, there was no significant main effect of alcohol consumption on cognitive functions. However, there was a significant interaction between alcohol consumption and ApoE ε4 status for GCA and episodic memory, such that the relationship of alcohol consumption and cognition was stronger in ε4 carriers. The ε4+ heavy drinking subgroup had the poorest GCA and episodic memory.


Presence of the ε4 allele may increase vulnerability to the deleterious effects of heavy alcohol consumption. Beneficial effects of light or moderate alcohol consumption were not observed.

Regular Research
Copyright © INS. Published by Cambridge University Press, 2020

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Drs. Kremen and Franz are joint senior authors.


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