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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 Open the ORCID record for Riki E. Slayday [Opens in a new window] ,
Daniel E. Gustavson ,
Jeremy A. Elman ,
Asad Beck ,
Linda K. McEvoy ,
Xin M. Tu ,
Bin Fang ,
Richard L. Hauger ,
Michael J. Lyons  and
Ruth E. McKenzie
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Riki E. Slayday
Affiliation:
Department of Psychology, San Diego State University, San Diego, CA, USA
Daniel E. Gustavson
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Jeremy A. Elman
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Asad Beck
Affiliation:
Graduate Program in Neuroscience, University of Washington, Seattle, WA, USA
Linda K. McEvoy
Affiliation:
Department of Radiology, University of California San Diego, La Jolla, CA, USA
Xin M. Tu
Affiliation:
Department of Family Medicine, University of California San Diego, La Jolla, CA, USA
Bin Fang
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
Richard L. Hauger
Affiliation:
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
Affiliation:
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
Ruth E. McKenzie
Affiliation:
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
Mark E. Sanderson-Cimino
Affiliation:
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
Affiliation:
Department of Biostatistics, St. Louis University, St. Louis, MO, USA
William S. Kremen
Affiliation:
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*
Affiliation:
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, CA 92093, USA. Tel: +1 858 822 1793. E-mail: cfranz@ucsd.edu
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Abstract

Objective:

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−).

Method:

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.

Results:

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.

Conclusions:

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.

Keywords

Middle agedMaleAgingApolipoprotein E4 (ApoE)Alcohol drinkingCognitive abilitiesRisk factors

Information

Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 27 , Issue 1 , January 2021 , pp. 56 - 68
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

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Footnotes

*

Drs. Kremen and Franz are joint senior authors.

References

Anttila, T., Helkala, E.L., Viitanen, M., Kareholt, I., Fratiglioni, L., Winblad, B., … Kivipelto, M. (2004). Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: A prospective population based study. BMJ, 329(7465), 539. doi: 10.1136/bmj.38181.418958.BECrossRefGoogle ScholarPubMed
Bloomfield, K., Grittner, U., Kramer, S., & Gmel, G. (2006). Social inequalities in alcohol consumption and alcohol-related problems in the study countries of the EU concerted action ‘Gender, culture and alcohol problems: A multi-national study’. Alcohol and Alcoholism, 41(suppl_1), i26–i36.CrossRefGoogle Scholar
Buschke, H. & Fuld, P.A. (1974). Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology, 24(11), 1019–1025. doi: 10.1212/wnl.24.11.1019CrossRefGoogle ScholarPubMed
Carmelli, D., Swan, G.E., Reed, T., Schellenberg, G.D., & Christian, J.C. (1999). The effect of apolipoprotein E epsilon4 in the relationships of smoking and drinking to cognitive function. Neuroepidemiology, 18(3), 125–133. doi: 10.1159/000026204CrossRefGoogle ScholarPubMed
Charlson, M.E., Pompei, P., Ales, K.L., & MacKenzie, C.R. (1987). A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. Journal of Chronic Diseases, 40(5), 373–383.CrossRefGoogle ScholarPubMed
Collins, S.E. (2016). Associations between socioeconomic factors and alcohol outcomes. Alcohol Research: Current Reviews, 38(1), 83.Google ScholarPubMed
Corella, D., Tucker, K., Lahoz, C., Coltell, O., Cupples, L.A., Wilson, P.W., … Ordovas, J.M. (2001). Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: The Framingham Offspring Study. Am J Clin Nutr, 73(4), 736–745. doi: 10.1093/ajcn/73.4.736CrossRefGoogle ScholarPubMed
Daneman, M. & Carpenter, P.A. (1980). Individual differences in working memory and reading. Journal of Verbal Learning and Verbal Behavior, 19(4), 450–466.CrossRefGoogle Scholar
Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-Kaplan executive function system: Technical manual: San Antonio, TX: Psychological Corporation.Google Scholar
Delis, D.C., Kramer, J.H., Kaplan, E., & Ober, B.A. (2000). California verbal learning test – Adult version: Manual (2nd ed.). San Antonio, TX: The Psychological Corporation.Google Scholar
Downer, B., Zanjani, F., & Fardo, D.W. (2014). The relationship between midlife and late life alcohol consumption, APOE e4 and the decline in learning and memory among older adults. Alcohol and Alcoholism, 49(1), 17–22. doi: 10.1093/alcalc/agt144CrossRefGoogle ScholarPubMed
Dufouil, C., Tzourio, C., Brayne, C., Berr, C., Amouyel, P., & Alperovitch, A. (2000). Influence of apolipoprotein E genotype on the risk of cognitive deterioration in moderate drinkers and smokers. Epidemiology, 11(3), 280–284.CrossRefGoogle ScholarPubMed
Eichner, J.E., Dunn, S.T., Perveen, G., Thompson, D.M., Stewart, K.E., & Stroehla, B.C. (2002). Apolipoprotein E polymorphism and cardiovascular disease: A HuGE review. American Journal of Epidemiology, 155(6), 487–495.CrossRefGoogle ScholarPubMed
Ekstrom, R.B., Dermen, D., & Harman, H.H. (1976). Manual for kit of factor-referenced cognitive tests (Vol. 102). Princeton, NJ: Educational Testing Service.Google Scholar
Elwood, P.C., Gallacher, J.E., Hopkinson, C.A., Pickering, J., Rabbitt, P., Stollery, B., … Bayer, A. (1999). Smoking, drinking, and other life style factors and cognitive function in men in the Caerphilly cohort. Journal of Epidemiology and Community Health, 53(1), 9–14. doi: 10.1136/jech.53.1.9CrossRefGoogle ScholarPubMed
Fillmore, K.M., Kerr, W.C., Stockwell, T., Chikritzhs, T., & Bostrom, A. (2006). Moderate alcohol use and reduced mortality risk: Systematic error in prospective studies. Addiction Research & Theory, 14(2), 101–132.CrossRefGoogle Scholar
Franz, C.E., Lyons, M.J., O’Brien, R., Panizzon, M.S., Kim, K., Bhat, R., … Kremen, W.S. (2011). A 35-year longitudinal assessment of cognition and midlife depression symptoms: The Vietnam Era Twin Study of Aging. The American Journal of Geriatric Psychiatry, 19(6), 559–570. doi: 10.1097/JGP.0b013e3181ef79f1CrossRefGoogle ScholarPubMed
Goldberg, J., Curran, B., Vitek, M.E., Henderson, W.G., & Boyko, E.J. (2002). The Vietnam era twin registry. Twin Research and Human Genetics, 5(5), 476–481.CrossRefGoogle ScholarPubMed
Golden, C. & Freshwater, S. (2002). Stroop color and word test adult version: A manual for clinical and experimental uses (2a ed.). Wood Dale, IL: Stoelting.Google Scholar
Gustavson, D.E., Panizzon, M.S., Elman, J.A., Franz, C.E., Reynolds, C.A., Jacobson, K.C., … Kremen, W.S. (2018). Stability of genetic and environmental influences on executive functions in midlife. Psychology and Aging, 33(2), 219–231. doi: 10.1037/pag0000230CrossRefGoogle ScholarPubMed
Hassing, L.B. (2018). Light alcohol consumption does not protect cognitive function: A longitudinal prospective study. Frontiers in Aging Neuroscience, 10, 81. doi: 10.3389/fnagi.2018.00081CrossRefGoogle Scholar
Herring, D., & Paulson, D. (2018). Moderate alcohol use and apolipoprotein E-4 (ApoE-4): Independent effects on cognitive outcomes in later life. Journal of Clinical and Experimental Neuropsychology, 40(4), 326–337. doi: 10.1080/13803395.2017.1343803CrossRefGoogle ScholarPubMed
Jack, C.R. Jr., Wiste, H.J., Weigand, S.D., Knopman, D.S., Vemuri, P., Mielke, M.M., … Petersen, R.C. (2015). Age, sex, and APOE epsilon4 effects on memory, brain structure, and beta-amyloid across the adult life span. JAMA Neurology, 72(5), 511–519. doi: 10.1001/jamaneurol.2014.4821CrossRefGoogle ScholarPubMed
Kalapatapu, R.K., Ventura, M.I., & Barnes, D.E. (2017). Lifetime alcohol use and cognitive performance in older adults. Journal of Addictive Diseases, 36(1), 38–47. doi: 10.1080/10550887.2016.1245029CrossRefGoogle ScholarPubMed
Kim, J.W., Lee, D.Y., Lee, B.C., Jung, M.H., Kim, H., Choi, Y.S., & Choi, I.G. (2012). Alcohol and cognition in the elderly: A review. Psychiatry Investigation, 9(1), 8–16. doi: 10.4306/pi.2012.9.1.8CrossRefGoogle ScholarPubMed
Kremen, W.S., Franz, C.E., & Lyons, M.J. (2013). VETSA: The Vietnam Era Twin Study of Aging. Twin Research and Human Genetics, 16(1), 399–402. doi: 10.1017/thg.2012.86CrossRefGoogle ScholarPubMed
Kremen, W.S., Thompson-Brenner, H., Leung, Y.M., Grant, M.D., Franz, C.E., Eisen, S.A., … Lyons, M.J. (2006). Genes, environment, and time: The Vietnam Era Twin Study of Aging (VETSA). Twin Research and Human Genetics, 9(6), 1009–1022. doi: 10.1375/183242706779462750CrossRefGoogle Scholar
Kuerbis, A., Moore, A.A., Sacco, P., & Zanjani, F. (2017). Alcohol and aging: Clinical and public health perspectives. Berlin: Springer.Google Scholar
Kumari, M., Holmes, M.V., Dale, C.E., Hubacek, J.A., Palmer, T.M., Pikhart, H., … Bobak, M. (2014). Alcohol consumption and cognitive performance: A Mendelian randomization study. Addiction, 109(9), 1462–1471. doi: 10.1111/add.12568CrossRefGoogle ScholarPubMed
Lamar, M., Yu, L., Rubin, L.H., James, B.D., Barnes, L.L., Farfel, J.M., … Schneider, J.A. (2019). APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults. Alzheimer’s & Dementia, 15(2), 258–266.CrossRefGoogle ScholarPubMed
Lindeman, R.D., Wayne, S.J., Baumgartner, R.N., & Garry, P.J. (2005). Cognitive function in drinkers compared to abstainers in the New Mexico elder health survey. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 60(8), 1065–1070.CrossRefGoogle ScholarPubMed
Lyons, M.J., Genderson, M., Grant, M.D., Logue, M., Zink, T., McKenzie, R., … Jerskey, B. (2013). Gene‐environment interaction of ApoE genotype and combat exposure on PTSD. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 162(7), 762–769.CrossRefGoogle Scholar
Lyons, M.J., York, T.P., Franz, C.E., Grant, M.D., Eaves, L.J., Jacobson, K.C., … Kremen, W.S. (2009). Genes determine stability and the environment determines change in cognitive ability during 35 years of adulthood. Psychological Science, 20(9), 1146–1152. doi: 10.1111/j.1467-9280.2009.02425.xCrossRefGoogle ScholarPubMed
Neafsey, E.J., & Collins, M.A. (2011). Moderate alcohol consumption and cognitive risk. Neuropsychiatric Disease and Treatment, 7, 465–484. doi: 10.2147/NDT.S23159CrossRefGoogle ScholarPubMed
Ngandu, T., Helkala, E.L., Soininen, H., Winblad, B., Tuomilehto, J., Nissinen, A., & Kivipelto, M. (2007). Alcohol drinking and cognitive functions: Findings from the Cardiovascular Risk Factors Aging and Dementia (CAIDE) Study. Dementia and Geriatric Cognitive Disorders, 23(3), 140–149. doi: 10.1159/000097995CrossRefGoogle ScholarPubMed
Oria, R.B., Patrick, P., Oriá, M., Lorntz, B., Thompson, M., Azevedo, O., … Lima, A. (2010). ApoE polymorphisms and diarrheal outcomes in Brazilian shanty town children. Brazilian Journal of Medical and Biological Research, 43(3), 249–256.CrossRefGoogle ScholarPubMed
Oria, R.B., Patrick, P.D., Blackman, J.A., Lima, A.A., & Guerrant, R.L. (2007). Role of apolipoprotein E4 in protecting children against early childhood diarrhea outcomes and implications for later development. Medical Hypotheses, 68(5), 1099–1107.CrossRefGoogle ScholarPubMed
Panza, F., Frisardi, V., Seripa, D., Logroscino, G., Santamato, A., Imbimbo, B.P., … Solfrizzi, V. (2012). Alcohol consumption in mild cognitive impairment and dementia: Harmful or neuroprotective? International Journal of Geriatric Psychiatry, 27(12), 1218–1238. doi: 10.1002/gps.3772CrossRefGoogle ScholarPubMed
Park, B., Park, J., Jun, J.K., Choi, K.S., & Suh, M. (2013). Gender differences in the association of smoking and drinking with the development of cognitive impairment. PLoS One, 8(10), e75095. doi: 10.1371/journal.pone.0075095CrossRefGoogle ScholarPubMed
Radloff, L.S. (1977). The CES-D scale: A self-report depression scale for research in the general population. Applied Psychological Measurement, 1(3), 385–401.CrossRefGoogle Scholar
Reas, E.T., Laughlin, G.A., Bergstrom, J., Kritz-Silverstein, D., Barrett-Connor, E., & McEvoy, L.K. (2019). Effects of APOE on cognitive aging in community-dwelling older adults. Neuropsychology, 33(3), 406.CrossRefGoogle ScholarPubMed
Richard, E.L., Kritz-Silverstein, D., Laughlin, G.A., Fung, T.T., Barrett-Connor, E., & McEvoy, L.K. (2017). Alcohol intake and cognitively healthy longevity in community-dwelling adults: The Rancho Bernardo study. Journal of Alzheimer’s disease, 59(3), 803–814. doi: 10.3233/JAD-161153CrossRefGoogle ScholarPubMed
Riedel, B.C., Thompson, P.M., & Brinton, R.D. (2016). Age, APOE and sex: Triad of risk of Alzheimer’s disease. The Journal of Steroid Biochemistry and Molecular Biology, 160, 134–147. doi: 10.1016/j.jsbmb.2016.03.012CrossRefGoogle ScholarPubMed
Sabia, S., Elbaz, A., Britton, A., Bell, S., Dugravot, A., Shipley, M., … Singh-Manoux, A. (2014). Alcohol consumption and cognitive decline in early old age. Neurology, 82(4), 332–339. doi: 10.1212/WNL.0000000000000063CrossRefGoogle ScholarPubMed
Schoenborn, C.A., & Heyman, K.M. (2009). Health characteristics of adults aged 55 years and over: United States, 2004–2007. National Health Statistics Reports, 16, 1–31.Google Scholar
Schultz, M.R., Lyons, M.J., Franz, C.E., Grant, M.D., Boake, C., Jacobson, K.C., … Kremen, W.S. (2008). Apolipoprotein E genotype and memory in the sixth decade of life. Neurology, 70(19 Part 2), 1771–1777.CrossRefGoogle ScholarPubMed
Servan-Schreiber, D., Cohen, J.D., & Steingard, S. (1996). Schizophrenic deficits in the processing of context: A test of a theoretical model. Archives of General Psychiatry, 53(12), 1105–1112.CrossRefGoogle ScholarPubMed
Skinner, J., Carvalho, J.O., Potter, G.G., Thames, A., Zelinski, E., Crane, P.K., … Alzheimer’s Disease Neuroimaging Initiative. (2012). The Alzheimer’s disease assessment scale-cognitive-plus (ADAS-Cog-Plus): An expansion of the ADAS-Cog to improve responsiveness in MCI. Brain Imaging and Behavior, 6(4), 489–501.CrossRefGoogle ScholarPubMed
Stroop, J.R. (1935). Studies of interference in serial verbal reactions. Journal of Experimental Psychology, 18(6), 643.CrossRefGoogle Scholar
Thurstone, L.L. (1944). A factorial study of perception. Chicago, IL: University of Chicago Press.Google Scholar
Topiwala, A., Allan, C.L., Valkanova, V., Zsoldos, E., Filippini, N., Sexton, C., … Ebmeier, K.P. (2017). Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: Longitudinal cohort study. BMJ, 357, j2353. doi: 10.1136/bmj.j2353CrossRefGoogle ScholarPubMed
Tsuang, M.T., Lyons, M.J., Eisen, S.A., Goldberg, J., True, W., Lin, N., … Eaves, L. (1996). Genetic influences on DSM-III-R drug abuse and dependence: A study of 3,372 twin pairs. American Journal of Medical Genetics, 67(5), 473–477.3.0.CO;2-L>CrossRefGoogle ScholarPubMed
U.S. Department of Health and Human Services and U.S. Department of Agriculture. (2015). 2015–2020 dietary guidelines for Americans. New York: Skyhorse Publishing Inc.Google Scholar
Uhlaner, J. & Bolanovich, D.J. (1952). Development of armed forces qualification test and predecessor army screening tests, 1946–1950. Washington, DC: Personnel Research Section, Department of the Army.CrossRefGoogle Scholar
Wechsler, D. (1997). Manual for the Wechsler Memory Scale—WMS-III (3rd ed.). San Antonio, TX: The Psychological Corporation.Google Scholar
Wechsler, D. (1999). Manual for the Wechsler abbreviated scale of intelligence. San Antonio, TX: Psychological Corporation.Google Scholar
World Health Organization. (2014). Global status report on alcohol and health, 2014: World Health Organization.Google Scholar
Wright, R.O., Hu, H., Silverman, E.K., Tsaih, S.W., Schwartz, J., Bellinger, D., … Hernandez-Avila, M. (2003). Apolipoprotein E genotype predicts 24-month bayley scales infant development score. Pediatric Research, 54(6), 819.CrossRefGoogle ScholarPubMed
Zanjani, F., Downer, B.G., Kruger, T.M., Willis, S.L., & Schaie, K.W. (2013). Alcohol effects on cognitive change in middle-aged and older adults. Aging & Mental Health, 17(1), 12–23. doi: 10.1080/13607863.2012.717254CrossRefGoogle ScholarPubMed
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