Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study
BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j2353 (Published 06 June 2017) Cite this as: BMJ 2017;357:j2353
All rapid responses
New concepts about so-called common sense are always challenging, not disregarding that it´s true observational studies likely provide the best available evidence or “the identification of harms when randomised controlled trials would seem unethical or impractical”(1).
In statistical hypothesis testing, a type I error is the incorrect rejection of a true null hypothesis. so is a "false positive", while a type II error is incorrectly retaining a false null hypothesis, i.e, a "false negative".
Simply put, a type I error is the false detection of an effect that is not present, while a type II error is the failure to detect an effect that is present. Emphasizing that in this study authored by Topiwala et al, because of the small number of subjects involved, and the always large 95% confidence intervals of alcohol-related brain health effects presented; a type 1 statistical error(2), could have happened, namely when using proxies or surrogates markers of diseases, in the occasions where exist today all kinds of non-alcoholic beverages for testing of pragmatic randomized clinical trials,(3).
Table of error types(2).
Table of error types Null hypothesis (H0) is
True False
Decision About Null Hypothesis (H0) Reject Type I error
(False Positive) Correct inference
(True Positive)
Fail to reject Correct inference
(True Negative) Type II error
(False Negative)
REFERENCES:
1. S. Barton. Which clinical studies provide the best evidence?
The best RCT still trumps the best observational study. BMJ. 2000 Jul 29; 321(7256): 255–256.
2. Sheskin, David (2004). Handbook of Parametric and Nonparametric Statistical Procedures. CRC Press. p. 54. ISBN 1584884401.
3. Laura A. Young, MD, PhD; John B. Buse, MD, PhD; Mark A. Weaver, PhD; Maihan B., et al, for the Monitor Trial Group . Glucose Self-Monitoring in Non–Insulin-Treated Patients With Type 2 Diabetes in Primary Care Settings. A Randomized Trial. JAMA Intern Med. doi:10.1001/jamainternmed.2017.1233 Published online June 10, 2017.
Competing interests: No competing interests
While the result in the right hippocampus of males appears intriguing, I cannot see clear a priori justification for restricting the analyses to this specific region of interest. Indeed the hippocampus is not among the regions mentioned in the introduction as previously implicated in alcohol-related structural brain changes. I would be interested to see more extensive reporting of the whole brain volumetric analysis to establish how specific the findings were to the hippocampus. The individual slices displayed in Figure 4 hint at some more extensive changes. Was the hippocampal result indicative of a more generalised pattern of atrophy throughout the brain (but perhaps more pronounced owing to its overall higher rate of neurogenesis)? If not, could the authors explain why the hippocampus was chosen for consideration in such great focus?
Competing interests: No competing interests
Moderate alcoholism is a well documented pathological reaction to unsolved grief said David Cook. Whether minimal or moderate drinking - it is a social disorder which exists because of the longing to live in a free world where the brain and functions do not ring together. The present study with its scientific approach showed that hippocampal function and the corpus callosum are affected by alcohol consumption. There is a drop in lexical fluency and probably acts as a safe mechanism for the alcoholics to lose control of bodily movement and verbal slurring.
As long as civilization exists, alcohol will remain as the elixir of life from whose clutches of temptation man becomes a victim. Alcohol may be the salt and pepper of life but the spice of life is lost in the mysterious effects of alcohol with a slow decline in cognitive function, followed by a decline in affective and psychomotor functions.
Competing interests: No competing interests
We often hear that moderate consumption of alcohol is beneficial for health. But is it? What happens to alcohol in our body?
A simple Google search reveals that alcohol metabolism involves the formation of two enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). These enzymes help break apart the alcohol molecule, making it possible to eliminate it from the body. First, ADH metabolises alcohol to acetaldehyde. a highly toxic substance and known carcinogen.
That Is enough for me to reject alcohol in any quantity, no matter how small, as a useful life supporting and safe substance.
Competing interests: No competing interests
As a linguist a and language learner, I have to point out that "fluency" is an established academic term with a completely different meaning.
I came across this article in an independent language learning community I belong to, where someone posted it to discuss alcohol's potential impact on SLA (second language acquisition). I have the following questions concerning the linguistic side of the tests:
-Were the tests done only in English? Were all the participants English native speakers?
-Was only standard English accepted? If someone used a word from a dialect or from another language, was it disregarded?
-Have you considered testing the communication skills in addition to the more abstract cognitive ones? A test similar to those used in language learning/teaching would be more relevant for showing how much one's actual language skills deteriorate.
Competing interests: No competing interests
A cohort, or follow-up study design seems, since the landmark Framingham Heart study(1), to be the best study design for identifying risk factors for increased, all-cause, cardiovascular disease mortalities, dementia in general, Alzheimer disease in particular, so-called type 2 diabetes, and some other non-communicable chronic diseases(2).
Charles Darwin has shown that all living species on earth have to pass through evolutionary survival in nature and print to the next generations the best genes for that (3). In the context of evolutionary laws, so far as the poet and songwriter, Bob Dylan, has composed: “the times they are a changin”….
The big advantage of the randomization process is controlling for confounders that we are not even aware were present at a given particular time. And that is why a well done prospective randomized clinical trial is considered the gold standard of evidence-based medicine.
In the present case, and in my humble opinion, it is urgently needed to do the best by comparing light to moderate alcohol drinking with active comparators such as non-alcoholic beer and non-alcoholic liquors, using balanced primary and secondary outcomes. This is because of this sort of “new but opposite” information to what has been so far established as “common sense” by large and repeated observational evidence as the “J” curve of survival all-cause and cardiovascular benefits of light to moderate drinking (4) is now presented in this study of Topiwala et al.
REFERENCES:
1. https://www.framinghamheartstudy.org/
2,http://www.joslin.org/info/Type_2_Diabetes_Know_Your_Risk_Factors.html
3. George C. Williams, Randolph M. Nesse. The Dawn of Darwinian Medicine. The Quaterly Review of Biology March 1991.
4. Peter L Thompson , MD, FRACP, FACC. J-curve revisited: cardiovascular benefits of moderate alcohol use cannot be dismissed. Medical Journal of Australia. May 6th. 2013. doi: 10.5694/mja12.10922.
Competing interests: No competing interests
Large observational evidence has consistently shown that light to moderate drinking decreases all-cause and cardiovascular disease mortality(1).
A large enough prospective, randomized, controlled clinical trial, with non-alcoholic beer&liquor as active comparators, would seem to be needed here.
REFERENCE:
1. Erin K. Howie, Xuemei Sui, Duck-chul Lee, Steven P. Hooker, James R. Hebert, ´ and Steven N. Blair, Alcohol Consumption and Risk of All-Cause and Cardiovascular Disease Mortality in Men. Journal of Aging Research. Volume 2011, Article ID 805062, 10 pages. doi:10.4061/2011/805062
Competing interests: No competing interests
Killian A. Welch stated In the Editorial [1] that epidemiological studies often report better health in moderate alcohol use compared with abstinence.
US Federal Dietary guidelines (2015-20) allow up to 24.5 units a week for men [2], one unit contains 8 g of alcohol. But in many countries there is a new trend to revise their guidelines.
Pre-2016 United Kingdom guidelines allow up to 21 units/week for men, 14 units for women, newly revised to 14 units/week for men and women.
In the observational cohort study of A. Topiwala and colleagues I´m missing some relevant points:
The distinction among the effects of different types of alcohol may be important.
A meta-analysis described the relationship between moderate drinking and aspects of cognition [3] and indicated that wine was better than beer or spirits, but this was based on a relatively small number of studies. There are reports about some protective molecules in red wine and benefits of red wine intake and cardiovascular risk, the well-known "French paradox"[4]. In contrast, Wilhelm J et al. [5] found a significant difference in hippocampal volumes between patients consuming different beverages (ANOVA: F = 7.454; df = 2; P = 0.0015) with the smallest hippocampal volumes in the wine group, followed by the spirits group. Furthermore, patients with a preferred spirits consumption showed significantly higher plasma homocysteine levels (ANOVA: F = 3.39; df = 2; P = 0.042). Homocysteine-mediated excitotoxicity may be an important pathophysiological mechanism in ethanol-related brain damage, particularly in patients consuming wine and spirits. The extent of brain atrophy in beer consuming patients seems to be more moderate.
The individual extent of structural brain tissue changes is influenced by a dose/duration effect of alcohol. This co factor was not analyzed in the presented study of Topiwala et al. in an adequate way. Was the time of drinking uniformly spread over a week or with times of heavy drinking with possible alcohol intoxication?
Heavy drinking was associated with higher cognitive risk for cognitive impairment and dementia, but investigations also showed that the presence of the apolipoprotein E epsilon 4 allele eliminated any possible benefit of light drinking.
This informations should be added.
1) Killian W “Alcohol consumption and brain health”. BMJ 2017;357:j2645
2) 2015-2020 Dietary Guidelines for Americans. 8th ed. 2015. https://health.gov/dietaryguidelines/2015/guidelines/xref-ref-8-1
3) Neafsey EJ, Collins MA. Moderate alcohol consumption and cognitive risk. Neuropsychiatr Dis Treat2011;357:465-84. doi:10.2147/NDT.S23159 pmid:21857787
4) Liberale L et al. Impact of Red Wine Consumption on Cardiovascular Health. Curr Med Chem. 2017 May 17. doi: 10.2174/0929867324666170518100606. [Epub ahead of print]
5) Wilhelm J et al. Hippocampal volume loss in patients with alcoholism is influenced by the consumed type of alcoholic beverage. Alcohol Alcohol. 2008; 4 3(3):296-9. doi: 10.1093/
Competing interests: No competing interests
Not for the first time, "epidemiologists" of today have demonstrated:
1. Their science is flawed.
2. The public cannot be expected to listen to their conclusions.
Your "moderate" may be my "immoderate".
Food and drink: allow me to go by my family history.
To those who fund this epidemiology I say - please spend your money on TREATING those who are ill.
To Her Majesty's right honourable ministers I say - please stop exporting your whisky and beer to the noveau riche of China, India, Africa. Let them make and drink their own poisons.
Declaration. I do take, with due gratitude to the powers above us, beneath us, in us, about a third of a litre of BAVARIAN beer on the day I arrive in Bavaria.
Competing interests: No competing interests
Re: Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study
Topiwala et al. found that alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy (1). However, they did not control for cannabis use or misuse. A systematic literature and meta-analysis of 14 studies found that chronic and long-term cannabis exposure may exert significant effects in brain areas on the white and grey matter structures of non-psychotic cannabis users, such as the hippocampus, which could be related to a neurotoxic action (2). Since the frequency of cannabis misuse is more frequent in subjects using regularly alcohol, compared to abstinent subjects, cannabis use or misuse can represent a bias in interpreting the results.
Topiwala et al. found a dose dependent relationship, and increased odds of hippocampal atrophy, even in moderate drinkers (14-<21 units/week = 112-<168g/week in men). These results question the current limits recommended in the US guidelines, which suggest that up to 24.5 units a week (=170g/week) is safe for men. These limits can be questioned in other countries as well.
There is a wide disparity in definitions of low-risk drinking around the world. In this regard, Kalinowski and Humphreys investigated standard drink definitions and low-risk alcohol consumption guidelines in 37 countries (3). While the limits recommended in the guidelines in some countries are below 112-<168g/week in men, e.g. in China (100g/week in men), the limits attain 168g/week in men in Austria, Denmark, Iceland, Mexico, or over 168g/week, e.g. in Ireland (170g/week), Spain (170g/week), France (210g/week), or Canada (204g/week) (3). The guidelines of these countries need to take into account the increased risk of adverse brain outcomes induced by moderate alcohol consumption.
1. Topiwala A, Allan CL, Valkanova V, Zsoldos E, Filippini N, Sexton C, Mahmood A, Fooks P, Singh-Manoux A, Mackay CE, Kivimäki M, Ebmeier KP. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017;357:j2353. doi: 10.1136/bmj.j2353.
2. Rocchetti M, Crescini A, Borgwardt S, Caverzasi E, Politi P, Atakan Z, Fusar-Poli P. Is cannabis neurotoxic for the healthy brain? A meta-analytical review of structural brain alterations in non-psychotic users.Psychiatry Clin Neurosci. 2013;67(7):483-92.
3. Kalinowski A, Humphreys K. Governmental standard drink definitions and low-risk alcohol consumption guidelines in 37 countries. Addiction. 2016;111(7):1293-8.
Competing interests: AD has received honoraria for lectures from AstraZeneca, Lunbeck, Lilly, and Otsuka.