Alcohol consumption

Introduction

Correlative studies have shown that regular consumption of a small amount of alcohol is linked to a number of health benefits, especially cardiovascular benefits, which, themselves, are correlated with reduced risk of dementia.

But the studies are not all consistent, and many researchers speculate that there are too many confounding factors to be able to adequately isolate the effect of alcohol consumption.

The question for ε4-carriers is whether APOE status modifies the relation between alcohol consumption and health effects. The answer is a fairly clear "yes". The principal question is whether alcohol is harmful to ε4-carriers, or merely non-beneficial. It appears that the best strategy for ε4-carriers, in general, when it comes to alcohol consumption, might be to avoid alcohol entirely, especially if the putative beneficial effects of alcohol (improved cholesterol profiles -- which may be yet another benefit that accrues only to non-ε4s) can be achieved by other means.

Why understanding alcohol consumption is important for E4s

Consumption of a small amount of alcohol (the equivalent of one drink for a typical woman, a bit more for a typical man) may reduce risk in non-ε4-carriers. In ε4-carriers (including ε3/ε4s; note though that ε2/ε4s have not been studied sufficiently), any amount of alcohol appears to be damaging according to some studies.

What the Research Says

• Regarding E4 and ethanol-induced neurotoxicity. (Li J, et al, 2017)

"Taken together, our results for the first time demonstrate that apoE4 and high-concentration ethanol synergistically enhance neurotoxicity through elevating cellular oxidative stress and increasing neuronal apoptosis, and support the notion that avoiding excessive alcohol consumption can help to prevent AD especially in APOE ε4 carriers."

• Here is a secondary analysis of cognitive, genetic (for ApoE4) and alcohol consumption data collected from members of the Framingham Heart Study Offspring Cohort. (Downer, B., et a, 2014)

"Light and moderate alcohol consumption during late life was associated with greater decline in learning and memory among APOE e4 carriers, whereas light and moderate alcohol consumption was associated with an increase in learning and memory among non-APOE e4 carriers."

• According to one often-cited study, ε4 teetotalers may have a lower risk than ε3s who never drink but not lower than ε3s who drink a little.(Anttila T, et al, 2004)

Results. "Participants who drank no alcohol at midlife and those who drank alcohol frequently were both twice as likely to have mild cognitive impairment in old age as those participants who drank alcohol infrequently. The risk of dementia related to alcohol drinking was modified by the presence of the apolipoprotein e4 allele. The carriers of apolipoprotein e4 had an increased risk of dementia with increasing alcohol consumption: compared with non-carriers who never drank [which, for them, is not as good as drinking a little bit], the odds ratio for carriers who never drank was 0.6 [emphasis added], for infrequent drinkers it was 2.3, and for frequent drinkers was 3.6 (the overall interaction term "drinking frequency*apolipoprotein e4" was significant (P = 0.04), as were the interactions "infrequent drinking*apolipoprotein e4" (P = 0.02) and "frequent drinking*apolipoprotein e4" (P = 0.03)). Non-carriers of apolipoprotein e4 had similar odds ratios for dementia irrespective of alcohol consumption."

Note, however, that the authors speculate that the infrequent drinkers may have been binge drinkers:

"Concerning alcohol drinking, it might also be that it is the drinking pattern which together with apoE ɛ4 carrier status forms a hazardous combination. At the time of the midlife assessment of the current study, it was a common habit in Finland to drink reasonable (sic) seldom (most drinkers drank only once of twice per month in the current data), but still, a large quantity of alcohol per each drinking session (i.e. binge drinking). This binge drinking habit might specifically interact with apoE ɛ4 and therefore, the increase in the dementia risk might be more pronouncedly seen among those persons carrying the apoE ɛ4 allele and classified as frequent drinkers in our study. These issues need to be further clarified in large cohort studies with more detailed information about alcohol consumption."

• A different study also finds that ε4 carriers have an increased risk of AD when they drink infrequently, compared to when they don't drink at all (3.78 odds ratio, with a 95% confidence interval of 0.94–15.24). Most of the findings are very similar to the above study. (Note that the same research team conducted both analyses, and the populations examined were drawn from the same cohort in Scandinavia, where "infrequent drinking" is likely to mean infrequent binge drinking.) (Kivipelto, M., et al, 2008)

"Compared with the ‘apoE ε4 non-carrier and never drinker’ group the ‘apoE ε4 carrier and never drinker’ group had an OR 0.67 (95% CI = 0.17–2.73), ‘apoE ε4 carrier and infrequent drinker’ group 2.36 (95% CI = 0.83–6.73) and ‘apoE ε4 carrier and frequent drinker’ group 3.82 (95% CI = 1.14–12.75) for dementia."

A deeper dive into the science

• "Alcohol and cognition in the elderly: a review" by Kim JW et. al..
• "Alcohol consumption in mild cognitive impairment and dementia: harmful or neuroprotective?" by Panza F et. al..
• "Moderate alcohol consumption and cognitive risk." by Neafsey EJ et. al.
• "Ethanol and cognition: indirect effects, neurotoxicity and neuroprotection: a review." by Brust JC.