The alcohol conundrum

There is no disagreement that excessive alcohol consumption is bad for the brain. A 2019 review  found that heavy alcohol use in humans was universally associated with an increased risk of all-cause dementia and reduced grey matter volume in brain imaging studies.  In animal models, chronic intake of moderate amounts of alcohol exacerbates behavioral and pathological Alzheimer’s-like changes in the brains of transgenic mice. These changes included increased amyloid plaque formation and Ab40 levels in CSF. Transgenic mice also exhibited deficits in nest building, a metric of self-care, as well as increased activity, even at moderate alcohol intake levels. 
 
So, what about moderate alcohol consumption in humans? This has been defined as two or less drinks per day in males and one drink or less in females. It is virtually impossible to do randomized, double-blind studies of the effects of alcohol in humans. This is because we know that alcohol can be neurotoxic, and it is arguably unethical to give a known toxin to randomly assigned volunteers. So instead of randomized, double-blind studies, we are left with a number of large, observational databank studies that rely on patient reporting. Many but not all of these studies, including this recent paper in JAMA Network Open, report that people who drink alcohol in the moderate range are less likely to later develop dementia than those who do not drink alcohol. Sounds great, right? Can moderate amounts of alcohol be protective? Sorry, the answer is probably not. The problem with these unrandomized and unblinded studies is in the lack accounting for bias. Sceptics point to the likelihood of abstainer bias: some non-drinkers and light drinkers may be already sick and therefore less likely to drink alcohol.
 
A recent paper published in eClinical Medicine “used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006–2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified from a meta-genome-wide association study of 941,280 people from Europe.” 

The authors conclude that “this study identified a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our findings suggested that there was no safe level of alcohol consumption for dementia.” I do not pretend to understand the epidemiological techniques used to reach this conclusion, and I can’t weigh in regarding the correctness of this analysis. But I suspect that it will turn out to be true. Until we have a more certain answer to the question of whether alcohol can help prevent dementia, I would recommend that those who already carry a dementia diagnosis should consider stopping all consumption of alcohol.  I have done just that and now enjoy one daily non-alcoholic beer (limited by law to contain no more than 1% alcohol). I don’t get a buzz anymore, but I do feel better about my brain.