Alcohol consumption: what impact on later life brain and cognition?

The media portrayal of the “archetypical” person at-risk for heavy and harmful alcohol use is the young male involved in an aggressive brawl or the young women falling out of a nightclub. However, recent figures suggest that drinking in older adults is increasing (Blazer and Wu, 2011), with those aged 55-64 years at the most risk of drinking at higher or increasing risk levels (NHS, 2017).

Whilst the detrimental health effects of alcohol on increased risk for liver disease, several types of cancer, heart disease are well-documented, the effects of alcohol on the brain, cognitive function and risk of dementia are less well-known and publicised.

There is a growing evidence base to suggest chronic heavy alcohol use is associated with increased risk for brain atrophy (brain shrinkage), dementia and cognitive decline (Alcohol Research UK, 2013). However, the picture is less clear with regards to moderate alcohol consumption, with mixed evidence highlighting both the detrimental effects and benefits of moderate alcohol consumption compared to abstinence on the brain and cognition. Recent concerns have been raised regarding the protective effects of moderate alcohol consumption, where studies have included former drinkers as abstainers and not considered the influence of confounding factors such as socioeconomic status.

The present clinical review (Topiwala and Ebmeier, 2018) therefore aimed to: (1) synthesise current evidence for the effects of chronic heavy alcohol use on brain and cognitive function and (2) disentangle the impact of moderation alcohol consumption.

There’s mixed evidence highlighting both the detrimental effects and benefits of moderate alcohol consumption compared to abstinence on the brain and cognition.

Methods

Databases including: MEDLINE, PubMed and Google Scholar were searched using the search terms “alcohol” AND (“dementia” OR “cognition” OR “brain”) until September 2017.

Results

The results are presented by chronic heavy and moderate alcohol consumption, focusing on cognitive impairment, dementia risk and brain structure.

Chronic heavy alcohol consumption

Dementia risk and cognitive impairment

A strong evidence base to support the association between chronic heavy alcohol consumption and increased dementia risk and cognitive decline

A prospective long-term study (Kuźma et al, 2014) indicated that individuals with a history of alcohol use disorder had more than double the odds of later severe memory impairment compared to controls (OR 2.21, 95% CI 1.27 to 3.85)

Prevalence of alcohol-related dementia estimates range from 9% to 22%

There is no clear evidence for what level of consumption is required to cause alcohol-related dementia. One study (Oslin et al, 1998) suggests a 5- year intake of greater than 35 units (280 grams) per week for males and 28 units (224 grams) for females.

Brain structure

Brain atrophy in chronic alcohol dependency is well documented

Studies report frontal cortex reductions of 23 % (Kril et al, 1999), widespread cortical atrophy, particularly affecting the frontal lobes (Chanraud et al, 2007), hippocampal loss (Bengochea et al, 1991) and reduced amygdala volume (Alvarez et al, 1989) in alcohol dependency

Other studies have demonstrated cerebellar atrophy (Ferrer et al 1984), effects on anterior thalamic nuclei (Harding et al, 1996) and loss of white matter in chronic alcohol abuse (Harper et al, 1985). One study reported that corpus callosum thickness was significantly reduced in alcohol dependent individuals compared to controls (Harper et al, 1985).

The review identified a large consistent evidence base for increased risk of dementia, cognitive impairment and brain atrophy in the context of chronic heavy alcohol consumption.

Moderate alcohol consumption

Dementia risk

Several large epidemiological studies report a reduced risk of dementia in light to moderate drinkers compared with abstainers

One study (Ruitenburg et al, 2002) found those drinking 2-6 units (14-46 grams) per day had a reduced risk of dementia compared with abstainers (HR 0.58, 95% CI 0.38 to 0.9)

Another (Orgogozo et al, 1997) reported light (2-4 units or 14-32 grams per day) and moderate (6-8 units or 46-64 grams per day) wine drinkers had reduced odds of incident Alzheimer’s disease. Similarly, Mukamal et al (2003) reported lower dementia risk in those drinking 2-11 units (14-84 grams) per day

Meta-analyses have also demonstrated a protective effect of light to moderate alcohol consumption on risk of dementia, with one (Anstey et al, 2009) indicating a pooled risk reduction of 25%–8% with late-life drinking.

Cognitive impairment

Studies have indicated better cognitive scores and less cognitive decline at 2-year follow-up for women drinking one drink per day (value in grams not reported) compared to non-drinkers (Stampfer et al, 2005) and less cognitive decline in minimal (2 units or 14 grams per month) to moderate drinkers (2 units or 14 grams per day) compared to abstainers (Ganguli et al, 2005)

Other studies have found no protective effect of light drinking on cognition (Lobo et al, 2010) or an increased risk of cognitive decline with increased alcohol use (Bos et al, 2017).

Brain structure

There is no human evidence for a convincing neural correlate for a protective effect of a small amount of alcohol on the brain, although this is a poorly studied area

While some studies have reported that moderate alcohol consumption in older adults is associated with reduced total brain volume and increased ventricle size (Ding et al, 2004), grey matter atrophy (Mukamal et al, 2001) and reduced frontal and partial grey matter density, others have not reported such effects (Gu et al, 2014) or only at higher alcohol intake (Kubota et al, 2001)

Similar mixed findings are reported for associations between moderate alcohol consumption and white matter, with some studies reporting increased white matter in moderate drinkers (De Bruin et al, 2005) and other showing the inverse relationship (Anstey et al, 2006)

A cohort neuroimaging study examining alcohol consumption over the preceding 30 years indicated a dose-dependent association between alcohol consumption and hippocampal atrophy, where 14-21 units (112-168 grams) per week was associated with three times odds of hippocampal atrophy compared with abstinence.

Summary of findings

The review identified a large consistent evidence base for increased risk of dementia, cognitive impairment and brain atrophy in the context of chronic heavy alcohol consumption. The review also addresses the potential mechanisms underlying alcohol-related brain atrophy, including: thiamine deficiency, neurotoxicity of ethanol and the cerebral effects of the liver not removing neurotoxic substances from the blood.

The evidence for the risk or benefits of lesser or “moderate” alcohol consumption was less clear, with mixed evidence for the protective effects of moderate consumption on cognition, dementia risk and brain structure.

The authors highlight cognitive function, dementia and neuroimaging may prove useful markers of excessive alcohol use in assessment of alcohol use disorders. They also indicate the need for further robust evidence examining the association between moderate consumption and brain structure and cognitive impairment, with future studies addressing the impact of potential confounding factors such as socioeconomic status and education. Mendelian randomisation is suggested as a promising technique for dealing with residual confounders.

The evidence for the risk or benefits of “moderate” alcohol consumption was less clear, with mixed evidence for the protective effects of moderate consumption on cognition, dementia risk and brain structure.

Strengths and limitations

The review addresses important concerns around the highly publicised protective benefits of moderate alcohol consumption on cognitive function and highlights that these are questionable and likely to be restricted to very small amounts of alcohol e.g. one unit per day or less. The review also highlights that clinical interactions and assessments in alcohol use disorders should include discussion of cognitive symptoms and adverse brain effects of alcohol, which should be informed by the latest research available.

Given the nature of the review (i.e. a clinical review rather than a systematic review or meta-analysis) it is difficult to scrutinise the design and quality of the studies discussed. For example, it was not clear for some studies who the participants were, how old they were at the time of screening/testing and what the primary outcomes of studies were.

As the authors point out, the definition of “moderate” alcohol consumption was highly variable between studies. The amount of alcohol consumed was also given in different units of measurement across studies. To help my own reading of this paper I converted studies which reported grams per day to units, with 8 grams = one unit of alcohol (NHS Choices, 2015). In studies included in the review, moderate alcohol consumption is reported between 2-11 units of alcohol per day. This is highly variable and very high in some studies, considering the weekly recommended alcohol intake by the UK government is 14 units per week. It was also not clear what “chronic heavy alcohol consumption” referred to in some studies, and whether participants in these studies met diagnosis for alcohol dependency or alcohol use disorders.

Some of the studies included in this review were over 20 years old, highlighting the need for further research in this area, especially given recent changes in alcohol guidelines in the UK and higher rates of older drinkers in the increasing risk drinking category. This is especially relevant to the study of moderate alcohol consumption, where more recent studies do not seem to indicate a trend for health benefits of moderate consumption, compared with earlier studies.

This review calls into question the recently publicised protective benefits of moderate alcohol consumption on cognitive function.

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The Mental Elf

Moderate and heavy alcohol consumption: what impact on later life brain and cognition?

Methods