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Drinking any amount of alcohol likely increases dementia risk
Even light drinking is unlikely to be protective; risk rises in tandem with quantity consumed
Drinking any amount of alcohol likely increases the risk of dementia, suggests the largest combined observational and genetic study to date, published online in BMJ Evidence Based Medicine.
Even light drinking—generally thought to be protective, based on observational studies—is unlikely to lower the risk, which rises in tandem with the quantity of alcohol consumed, the research indicates.
Current thinking suggests that there might be an ‘optimal dose’ of alcohol for brain health, but most of these studies have focused on older people and/or didn’t differentiate between former and lifelong non-drinkers, complicating efforts to infer causality, note the researchers.
To try and circumnavigate these issues and strengthen the evidence base, the researchers drew on observational data and genetic methods (Mendelian randomisation) from two large biological databanks for the entire ‘dose’ range of alcohol consumption.
These were the US Million Veteran Program (MVP), which includes people of European, African, and Latin American ancestry, and the UK Biobank (UKB), which includes people of predominantly European ancestry.
Participants who were aged 56–72 at baseline, were monitored from recruitment until their first dementia diagnosis, death, or the date of last follow-up (December 2019 for MVP and January 2022 for UKB), whichever came first. The average monitoring period was 4 years for the US group, and 12 for the UK group.
Alcohol consumption was derived from questionnaire responses—over 90% of participants said they drank alcohol—and the Alcohol Use Disorders Identification Test (AUDIT-C) clinical screening tool. This screens for hazardous drinking patterns, including the frequency of binge drinking (6 or more drinks at a time).
In all, 559,559 participants from both groups were included in observational analyses, 14,540 of whom developed dementia of any type during the monitoring period:10,564 in the US group; and 3976 in the UK group. And 48,034 died: 28,738 in the US group and 19,296 in the UK group.
Observational analyses revealed U-shaped associations between alcohol and dementia risk: compared with light drinkers (fewer than 7 drinks a week) a 41% higher risk was observed among non-drinkers and heavy drinkers consuming 40 or more drinks a week, rising to a 51% higher risk among those who were alcohol dependent.
Mendelian randomisation genetic analyses drew on key data from multiple large individual genome-wide association studies (GWAS) of dementia, involving a total of 2.4 million participants to ascertain lifetime (rather than current) genetically predicted risks.
Mendelian randomisation leverages genetic data, minimising the impact of other potentially influential factors, to estimate causal effects: genomic risk for a trait (in this case, alcohol consumption) essentially stands in for the trait itself.
Three genetic measures related to alcohol use were used as different exposures, to study the impact on dementia risk of alcohol quantity, as well as problematic and dependent drinking.
These exposures were: self-reported weekly drinks (641 independent genetic variants); problematic ‘risky’ drinking (80 genetic variants); and alcohol dependency (66 genetic variants).
Higher genetic risk for all 3 exposure levels was associated with an increased risk of dementia, with a linear increase in dementia risk the higher the alcohol consumption.
For example, an extra 1-3 drinks a week was associated with a 15% higher risk. And a doubling in the genetic risk of alcohol dependency was associated with a 16% increase in dementia risk.
But no U-shaped association was found between alcohol intake and dementia, and no protective effects of low levels of alcohol intake were observed. Instead, dementia risk steadily increased with more genetically predicted drinking.
What’s more, those who went on to develop dementia typically drank less over time in the years preceding their diagnosis, suggesting that reverse causation—whereby early cognitive decline leads to reduced alcohol consumption—underlies the supposed protective effects of alcohol found in previous observational studies, say the researchers.
They acknowledge that a principal limitation of their findings is that the strongest statistical associations were found in people of European ancestry, because of the numbers of participants of this ethnic heritage studied. Mendelian randomisation also relies on assumptions that can’t be verified, they add.
Nevertheless, they suggest that their findings “challenge the notion that low levels of alcohol are neuroprotective.”
And they conclude: “Our study findings support a detrimental effect of all types of alcohol consumption on dementia risk, with no evidence supporting the previously suggested protective effect of moderate drinking.
“The pattern of reduced alcohol use before dementia diagnosis observed in our study underscores the complexity of inferring causality from observational data, especially in ageing populations.
“Our findings highlight the importance of considering reverse causation and residual confounding in studies of alcohol and dementia, and they suggest that reducing alcohol consumption may be an important strategy for dementia prevention.”
Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Prof Sir David Spiegelhalter, Emeritus Professor of Statistics, University of Cambridge, comments:
“The reporting of this study is misleading. The authors say that "genetic analysis showed a monotonic increasing dementia risk with increased alcohol intake.". This is untrue. The relationship is with genetically predicted alcohol intake - the actual alcohol consumption is not part of this analysis. And those genetic predictions rely on many unverifiable assumptions, as the authors acknowledge."
Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Group Leader in the UK Dementia Research Institute, and Past President of the British Neuroscience Association, comments:
“This study by Topiwala and colleagues at Oxford examining the relationship between alcohol use and risk of developing dementia is well-conducted. The authors looked at data from over 500,000 people who provided self-reports of how much they drank and compared this to their risk of developing dementia over time. Further they examined genetics from over 2 million people and compared genetic markers associated with alcohol use and genetic markers associated with increased risk.
“In both parts of the study, scientists observed that higher reported or predicted alcohol use was associated with increased risk or predicted risk of dementia. In the self-reporting study, people who reported consuming small amounts of alcohol (less than 7 drinks per week) had lower risk than heavy drinkers (more than 40 drinks per week). Interestingly, in this part of the study, non-drinkers and people who reported never drinking actually had similar risk of dementia to people who drank heavily.
“In the genetic study, genes predicting higher alcohol consumption were associated with genes predicting higher dementia risk. Unlike the self-reporting part of the study, genes predicting low alcohol intake were not associated with genes predicting low dementia risk. The authors attribute the difference between the parts of the study to people reducing alcohol intake in the early stages of dementia, but this does not explain the increased risk in people who report never drinking.
“Authors rightly acknowledge several important limitations of the study. Self-reported alcohol use may not be accurate, particularly if people have memory problems in early stages of dementia, and the genetic markers used as predictors of both alcohol intake and dementia are not perfect.
“Neither part of the study can conclusively prove that alcohol use directly causes dementia, but this adds to a large amount of similar data showing associations between alcohol intake and increased dementia risk, and fundamental neuroscience work has shown that alcohol is directly toxic to neurons in the brain.”
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