alcohol

Low levels of alcohol good for the brain

A mouse study found that high levels of alcohol over a long period of time were associated with high levels of a marker for inflammation, along with impaired cognition and motor skills.

However, those exposed to low levels of alcohol consumption, analogous to approximately 2 ½ drinks per day, actually showed less inflammation in the brain and their glymphatic system was more efficient in moving CSF through the brain and removing waste, compared to control mice who were not exposed to alcohol. Their cognitive performance also matched that of the controls.

The finding adds to a growing body of research that point to the health benefits of low doses of alcohol. While excessive consumption of alcohol is a well-documented health hazard, many studies have linked lower levels of drinking with a reduced risk of cardiovascular diseases as well as a number of cancers.

Reference: 

Lundgaard, I., Wang, W., Eberhardt, A., Vinitsky, H. S., Reeves, B. C., Peng, S., Lou, N., Hussain, R., & Nedergaard, M. (2018). Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function. Scientific Reports, 8(1), 2246. https://doi.org/10.1038/s41598-018-20424-y

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Alcohol levels that don’t damage the brain may be lower than thought

A British study following 550 adults over 30 years from 1985 has found that those who reported higher levels of alcohol consumption were more often found to have a shrunken hippocampus, with the effect greater for the right side of the brain. Such shrinkage was found in 35% of those who didn’t drink, but 65% for those who drank an average 2-3 units daily, and 77% for those who drank 30 or more units a week.

The structure of white matter was also linked to how much individuals drank.

Those who drank more did worse on a test of lexical fluency (“Name as many words starting with (a letter) as you can in a minute”), however no differences were found in performance in other tasks such as word recall, or naming words in a specific category, so that seems oddly specific.

Factors such as age, sex, social activity and education, were taken into account in the analysis. However, the majority of the study’s participants were men, and self-reports of alcohol consumption are often inaccurate with people underestimating how much they drink.

Perhaps the most important conclusion to draw from this study is that alcohol consumption of up to 13 units weekly was not associated with these negative changes – so rather than taking this as evidence of challenge to the research supporting moderate drinking, it should perhaps be taken as evidence of where the line should be drawn.

Units are defined as 8g of alcohol. In the U.S., a typical 12-ounce beer or 5-ounce glass of wine contains 14 g of alcohol.

Reference: 

Topiwala A et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: Longitudinal cohort study. BMJ 2017 Jun 6; 357:j2353. http://dx.doi.org/10.1136/bmj.j2353

Welch KA.Alcohol consumption and brain health: Even moderate drinking is linked to pathological changes in the brain. BMJ 2017 Jun 6; 357:j2645. http://dx.doi.org/10.1136/bmj.j2645

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If you flush when you drink alcohol, drinking may increase your risk of Alzheimer’s

Research using human cell cultures and mice suggests that those with an uncommon variation of the aldehyde dehydrogenase 2 gene (ALDH2) may be more at risk of Alzheimer's if they consume alcohol. This gene variation is associated with facial redness following alcohol consumption, reflecting reduced activity of an enzyme that protects against a toxin produced by alcohol consumption (acetaldehyde). Flushing, and inflammation, is a response to the toxin.

The gene variant occurs in about 8% of the world’s population, but is particularly prevalent among people from East Asia, where nearly half the population carries it.

The research builds on previous epidemiological studies in East Asian populations that have previously suggested an association between the mutation in ALDH2 that causes facial flushing and Alzheimer’s disease. However, there have also been other studies that didn’t find an association.

Confirmation of these results requires large epidemiological studies of humans to see whether alcohol drinkers who have the mutation develop Alzheimer’s disease at a higher-than-average rate.

The gene variant is also associated with a higher risk of developing cancer in the esophagus.

Reference: 

Joshi, A.U., Van Wassenhove, L.D., Logas, K.R. et al. Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s disease related pathology. acta neuropathol commun 7, 190 (2019). https://doi.org/10.1186/s40478-019-0839-7

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Light drinking may protect brain function

A 10-year study involving 19,887 middle-aged and older Americans, who completed surveys every two years about their health and lifestyle, has found that those who had a drink or two a day tended to show less cognitive decline, compared to non-drinkers.

Cognitive function was measured in a series of tests looking at their overall mental status, word recall and vocabulary. Their test results were combined to form a total cognitive score.

Age, smoking and education level were controlled for.

However, it is still hard to say whether the link is causal or correlational. The researchers do not encourage anyone to start drinking in order to prevent cognitive function decline.

The association was also stronger among white participants versus African American participants, which perhaps adds weight to the view that the association is correlational, that is, linked to other behaviors which are the true reason.

Reference: 

Zhang R, Shen L, Miles T, et al. Association of Low to Moderate Alcohol Drinking With Cognitive Functions From Middle to Older Age Among US Adults. JAMA Netw Open. 2020;3(6):e207922. doi:10.1001/jamanetworkopen.2020.7922

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Healthy lifestyle associated with lower dementia risk regardless of genes

  • A very large study found that an unhealthy lifestyle and high genetic risk were independently associated with higher dementia risk, and a healthy lifestyle reduced the risk for those at high genetic risk.

Data from 196,383 older adults (60+; mean age 64) in the UK Biobank found that a healthy lifestyle was associated with lower dementia risk regardless of genes.

Both an unhealthy lifestyle and high genetic risk were associated with higher dementia risk.

Lifestyle factors included smoking, physical activity, diet, and alcohol consumption. Bearing in mind that lifestyle factors were self-reported, 68.1% followed a healthy lifestyle, 23.6% were intermediate, and 8.2% followed an unhealthy lifestyle. Regarding genes, 20% were at high risk, 60% were intermediate, and 20% were at low risk.

Of those at high genetic risk, 1.23% developed dementia in the 8-year period (remember that these are people who are still relatively — the average age at study end would still only be 72), compared with 0.63% of those at low genetic risk. Of those at high genetic risk plus an unhealthy lifestyle, 1.78% developed dementia compared to 0.56% of those at low risk with a healthy lifestyle. Among those who had a high genetic risk but a healthy lifestyle, 1.13% developed dementia in the period.

I trust that these people will continue to be followed — it will be very interesting to see the statistics in another 10 years.

There were 1,769 new cases of dementia during the 8-year study period.

https://www.eurekalert.org/pub_releases/2019-07/jn-ihl071219.php

https://www.theguardian.com/society/2019/jul/14/healthy-lifestyle-may-cut-risk-of-dementia-regardless-of-genes

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Is there really a level at which alcohol benefits cognition?

  • A very large study of adults aged 40-73 found evidence that alcohol's suggested benefit for cognition applies to a much lower level of alcohol consumption than previously claimed — only one drink a day.
  • Another longitudinal study that also removed the bias that's thought to come from including non-drinkers in the analysis, found no evidence for any cognitive benefits at any level of alcohol consumption.

Large study shows level of beneficial alcohol consumption much lower than thought

A UK study using data from 13,342 middle-aged and older adults (40-73) has found that having up to one standard unit of alcohol a day improved reaction time, but more than that amount harmed cognitive performance. The effect was more pronounced in older adults.

While several studies have suggested a U-shaped relationship between alcohol and cognition, with light to moderate consumption being beneficial to older adults, this has been quite controversial, with little consensus on how much is too much.

This study uses data from the over half a million people who participated in the UK Biobank prospective cohort study. Of these, 20,346 undertook a repeat assessment 5 years after the initial assessment. The study excluded any who disclosed a history of neurological disorder, and then included only those who consumed alcohol at least once a week. Weekly drinkers had lower levels of socioeconomic deprivation, were more likely to hold a university degree, and to be male.

Cognitive performance was assessed very simply, using a 'stop-go' reaction time task. RT decreased as alcohol consumption increased up to 10g/day, and then increased after that point. This harmful effect became stronger as people got older.

This level of 10 g/day is markedly lower than that suggested by other studies, which have variously argued for: up to 40g for women and 80g for men; up to 34g for middle-aged adults; no more than 16g.

The study omitted people who didn't drink at all, because of the 'sick quitter' effect — it's been argued that the apparent connection between moderate alcohol consumption and better health and cognition is due to bias in the control group, with many people abstaining or quitting due to health issues, and this has been supported by some recent studies. For example, a 2016 review and meta-analysis found no significant difference in mortality for low-volume drinkers once abstainer biases were adjusted for.

The main takeaway from this study — which seems quite robust given the scale of the study — is that the level of 'positive' alcohol consumption is much lower than previously claimed.

The study is open access, and can be read in its entirety at https://academic.oup.com/jpubhealth/article/40/2/304/4793394

Study shows no benefits from alcohol consumption once abstainer bias accounted for

Another longitudinal study, using a subset of participants in the Swedish Twin Registry, found no evidence for any cognitive benefits at any level of alcohol consumption.

Participants were those 486 individuals who had been surveyed on their alcohol intake in their midlife (in 1967), and also taken part in cognitive assessments 25 years later. Cognitive tests occurred at 2-year intervals for the next 10 years.

The study found a significant negative dose-response association between alcohol intake in midlife and performance on the MMSE and tests of episodic memory. There was no significant association with semantic memory and spatial ability.

As with the other study, in order to remove abstainer bias, non-drinkers were excluded from the analysis. There were 181 non-drinkers, and this group were more likely to be women, to have less education, lower socioeconomic status, higher BMI, and were more likely to have diabetes and hypertension. They did indeed perform worse on all cognitive tests, but as you can see, most of the characteristics of this group do lend themselves to such a result.

Midlife alcohol consumption was used because it was assumed that this would give a better reflection of lifetime habits than that reported in old age. As it happened, there were no heavy drinkers in the cohort — the highest consumption was 15 units/week. In this study, 1 unit corresponded to 12g.

The study is open access, and can be read in its entirety at https://www.frontiersin.org/articles/10.3389/fnagi.2018.00081/full

Reference: 

Giovanni Piumatti, Simon C Moore, Damon M Berridge, Chinmoy Sarkar, John Gallacher, The relationship between alcohol use and long-term cognitive decline in middle and late life: a longitudinal analysis using UK Biobank, Journal of Public Health, Volume 40, Issue 2, June 2018, Pages 304–311, https://doi.org/10.1093/pubmed/fdx186

Hassing, L. B. (2018). Light Alcohol Consumption Does Not Protect Cognitive Function: A Longitudinal Prospective Study. Frontiers in Aging Neuroscience, 10. https://doi.org/10.3389/fnagi.2018.00081

 

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Alcohol & dementia risk

  • A rat brain cell study provides evidence that alcohol may increase Alzheimer's risk by impeding the removal of amyloid-beta protein.
  • A very large French study found that 38% of early-onset dementia cases were directly alcohol-related and 18% had an additional diagnosis of alcohol use disorders.

How alcohol increases Alzheimer's risk

A cell-culture study using rodent microglia found that some of the genes affected by alcohol and inflammation are also implicated in processes that clear amyloid beta, suggesting that alcohol may impede the clearance of amyloid beta in the brain.

In the study, rat microglial cells were exposed either to alcohol, pro-inflammatory chemicals called cytokines, or alcohol and cytokines, for 24 hours. Gene expression was altered for 312 genes under the alcohol condition; for 3,082 for the pro-inflammatory condition, and 3,552 for the alcohol and pro-inflammatory condition. Changes in gene expression ranged from a 50% decrease to a 72% increase. Many of the genes were involved in phagocytosis; just a handful of genes were involved in both phagocytosis and inflammation.

https://www.eurekalert.org/pub_releases/2018-06/uoia-hda060418.php

Chronic heavy drinking trebles dementia risk

Data from the French National Hospital Discharge database, involving over a million people diagnosed with dementia between 2008 and 2013, found that 38% of the 57,000 cases of early-onset dementia were directly alcohol-related and 18% had an additional diagnosis of alcohol use disorders.

Overall, alcohol use disorders were associated with a three times greater risk of all types of dementia.

The study only looked at people admitted to hospital due to chronic heavy drinking, so it will understate the link between alcohol use and dementia risk.

Moreover, heavy drinkers who had given up alcohol for a time did not reduce their dementia risk (although they were less likely to die early).

https://www.eurekalert.org/pub_releases/2018-02/cfaa-lso022018.php

https://www.theguardian.com/society/2018/feb/20/chronic-heavy-drinking-leads-to-serious-risk-of-dementia-study-warns

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The right diet may slow cognitive decline in stroke survivors

  • An observational study involving over 100 stroke survivors suggests the MIND diet may help substantially slow cognitive decline in those impaired by stroke.

A pilot study involving 106 participants of the Rush Memory and Aging Project who had experienced a stroke followed participants for an average of 5.9 years, testing their cognitive function and monitoring their eating habits using food journals. It was found that those whose diets scored highest on the MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) diet score had substantially slower rates of cognitive decline than those who scored lowest. The estimated effect of the diet remained strong even after taking into account participants' level of education and participation in cognitive and physical activities. Those who instead scored high on the Mediterranean or DASH diets did not show the same slower decline.

Both the Mediterranean and DASH diets have been shown to be protective against coronary artery disease and stroke, but this finding suggests the MIND diet is better for overall brain health.

The MIND diet is a hybrid of the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets. It has 15 components: 10 “brain-healthy food groups” and five unhealthy groups (red meat, butter, cheese, pastries and sweets, and fried or fast food).

To adhere to the MIND diet, you need to

  • eat at least three daily servings of whole grains
  • eat a green leafy vegetable and one other vegetable every day
  • drink a regular glass of wine
  • snack most days on nuts
  • have beans every other day or so
  • eat poultry and berries at least twice a week
  • eat fish at least once a week
  • limit butter to less than 1 1/2 teaspoons a day
  • eat less than 5 servings a week of sweets and pastries
  • eat less than one serving per week of whole fat cheese, and fried or fast food.

The researchers stress that this is a preliminary study, observational only. They are currently seeking participants for a wider, intervention study.

https://www.eurekalert.org/pub_releases/2018-01/rumc-mdm012418.php

Reference: 

Laurel J. Cherian & Martha Clare Morris: Presentation at the American Stroke Association's International Stroke Conference 2018 in Los Angeles, January 25.

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