MCI, Heavy Drinking a Hazardous Cocktail?

Damian McNamara

September 30, 2019

The combination of mild cognitive impairment (MCI) and heavy drinking is associated with an increased risk for progression to dementia, new research shows.

Results from a large, prospective cohort study showed that individuals with MCI who consumed an average of more than 14 alcoholic drinks per week were 72% more likely to experience progression to dementia compared to their counterparts with MCI who drank less than 1 drink per week.

For study participants who did not have MCI, no amount of alcohol consumption was significantly associated with a higher dementia risk.

"The associations between alcohol consumption and dementia risk were statistically significantly different when comparing participants with and without mild cognitive impairment at study start. This indicates that alcohol intake is not related to future dementia risk in the same way in these two groups of older adults," first author Manja Koch, PhD, research associate, Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, told Medscape Medical News.

"Physicians caring for older adults need to assess the full dimensions of drinking behavior ― including how much and how often ― and cognition when providing guidance to patients," senior study author Majken K. Jensen, PhD, associate professor of nutrition, Harvard T. H. Chan School of Public Health, added. "Advice to patients with MCI should acknowledge the lack of clear evidence of safety in this population."

The study was published online September 27 in JAMA Open.

Understudied Patient Population

Previous studies have shown that individuals who consume moderate amounts of alcohol have a lower risk for dementia compared to nondrinkers. "However, substantial heterogeneity in the observed associations exists, and several aspects remain unclear," the researchers note.

In addition, there is a question as to whether the link between alcohol consumption and dementia differs among older adults who have MCI.

"So far, few studies have assessed alcohol consumption and dementia specifically among participants with MCI," Jensen said.

To learn more, the investigators examined data for 3021 participants in the Ginkgo Evaluation of Memory Study (GEMS). The randomized, double-blind, controlled trial enrolled older participants from 2000 to 2008.

Investigators assessed cognitive and functional performance during follow-up and analyzed outcomes from July 2017 to June 2018. Comprehensive neuropsychological testing was conducted using the Modified Mini–Mental State Examination (3MSE), the Clinical Dementia Rating scale, and the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-Cog).

The median age of the participants was 78 years, and 46% were women. More than half of the cohort, 58%, reported consuming alcohol at baseline.

Categories of alcohol consumption in the study included none, fewer than 1.0 drinks per week, 1.0 to 7.0 drinks per week, 7.1 to 14.0 drinks per week, and more than 14.0 drinks per week.

No Proof of Causality

During the median follow-up of 6.0 years, 512 participants developed dementia, including 348 people with Alzheimer disease.

Among those with MCI at baseline, the hazard ratio (HR) for dementia was 1.72 (95% confidence interval [CI], 0.87 – 3.40) for those who consumed more than 14.0 drinks per week compared to those who consumed less than 1.0 drink per week.

In contrast, the investigators found that among participants who did not have MCI at study entry, there was no increased risk for dementia associated with any amount of alcohol in comparison with those who reported consuming fewer than 1.0 drink per week.

"When interpreting these findings, it is important to note that we cannot prove causality, that alcohol consumption was self-reported, and that we were not able to study the risks associated with heavy drinking," Koch said.

The researchers also found no significant association when they conducted a formal test of linear trend of dementia risk with respect to numbers of alcoholic drinks per week (HR, 1.02; 95%CI, 0.99 – 1.05; P = 0.13).

Age, sex, and APOE genotype did not change the relationship between alcohol consumption and dementia or Alzheimer disease risk.

How people drank alcohol made a difference. Daily, low-quantity drinking was associated with a lower dementia risk (HR, 0.45; 95% CI, 0.23 – 0.89; P = .02) compared with frequent, higher-quantity drinking.

MCI also significantly modified the association between alcohol intake and 3MSE scores at baseline (P for interaction = .02).

More Research Needed

Among participants who had MCI at baseline, those who reported consuming more than 14.0 drinks per week had statistically significantly lower 3MSE scores at follow-up compared with participants who consumed fewer than 1.0 drink per week. This between-group difference was −3.49 points (95% CI, −5.72 to −1.27 points).

The underlying biological mechanisms that link alcohol consumption to dementia risk "are not fully understood," Jensen said. "However, alcohol is known to be neurotoxic in heavy amounts. The underlying pathological processes that lead to mild cognitive impairment might make remaining brain cells even more susceptible to alcohol, but this requires further research."

Of note, nearly one half of participants with MCI reported current alcohol consumption, suggesting that it is "not an infrequent behavior," the researchers note.

"Our findings on alcohol and cognition are generally similar to previous studies," Jensen said.

A 2017 meta-analysis suggested a U-shaped relationship, with lowest risk at 4 drinks per week, whereas drinking 23 or more drinks per week was associated with a higher dementia risk.

"Those results are generally consistent with our findings among participants without baseline mild cognitive impairment," she added.

In the current study, the investigators were unable to examine potential associations with even higher alcohol intake. The study population of individuals aged 72 years or older "had a limited range of alcohol intake; thus, we cannot know what results would look like for heavier drinking," Koch said.

"Our findings warrant additional studies to confirm if even consumption of light to moderate amounts of alcohol as compared with nondrinking may be associated with an increased risk of cognitive decline in adults with mild cognitive impairment," Jensen said.

"We intend to continue studying this interesting group of individuals to determine the full range of factors that may determine their risk of dementia," Koch added. "This will help to better tailor advice and prevention to those most at risk."

Confirmatory Findings

Commenting on the findings for Medscape Medical News, Michaël Schwarzinger, MD, PhD, of the Translational Health Economics Network (THEN) in Paris, France, said the main results were not significant because the study was underpowered.

"My overall impression is that the main results of the study are not significant, but the authors present them and discuss them almost as if they were. The lack of statistical power is most likely due to the selection of the study population in a clinical trial," Schwarzinger said.

Schwarzinger noted that earlier research by his team, which was previously reported by Medscape Medical News, showed that individuals who had a history of alcohol use disorders were at threefold increased risk for dementia. In addition, the researchers found that more than 50% of those with early-onset dementia had a history of alcohol problems.

Schwarzinger noted that in the current study, categorization of participants with a maximum alcohol consumption of fewer than 14 drinks per week is "most likely reflective of a rather healthy group, as suggested by similar death rates across all five categories."

In contrast, no details were provided on nondrinkers who may formerly have been unhealthy drinkers. The rate of diabetes was higher among nondrinkers, Schwarzinger said.

Citing a 2016 systematic review and meta-analysis, he also noted "similar misclassification problems generally lead to the debatable conclusion that moderate drinking is good for health."

Also commenting on the findings for Medscape Medical News, Prof Clive Ballard of the University of Exeter Medical School, United Kingdom, noted that "the potential relationship of alcohol consumption to dementia is an important area."

However, he added, the current study "was relatively modest in size. The specific impact of alcohol in people with MCI is novel, but the study was underpowered to look at this. The added risk of 14 drinks per week confirms previous work but doesn’t add much.

"So overall, this feels like a useful, but confirmatory, study. The specific question of alcohol in people with MCI needs further work and is important," he said.

The study was supported by grants from the National Center for Complementary and Alternative Medicine, the National Institute of Neurological Disorders and Stroke, the Office of Dietary Supplements of the National Institute on Aging, the National Heart, Lung, and Blood Institute, the University of Pittsburgh Alzheimer's Disease Research Center, the Roena Kulynych Center for Memory and Cognition Research, Wake Forest University School of Medicine. The authors, Schwarzinger, and Ballard have disclosed no relevant financial relationships.

JAMA Open. Published online September 27, 2019. Full text

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