Critique 036: Alcohol consumption after age 75 associated with lower risk of developing dementia ———7 March 2011

Weyerer S, Schaufele M, Wiese B, Maier W, Tebarth F, van den Bussche H, Pentzek M, Bickel H, Luppa M, Riedel-Heller SG, for the German AgeCoDe Study Group (German Study on Ageing, Cognition and Dementia in Primary Care Patients). Current alcohol consumption and its relationship to incident dementia: results from a 3-year follow-up study among primary care attenders aged 75 years and older. Age and Ageing 2011; 0: 1–7; doi: 10.1093/ageing/afr007.

Authors’ Abstract

Objective: to investigate prospectively the relationship between current alcohol consumption (quantity and type of alcohol) and incident overall dementia and Alzheimer dementia.

Method: the study is based on individuals (75+) attending general practitioners in Germany: 3,202 subjects free of dementia were studied at baseline, 1.5 years and 3 years later by means of structured clinical interviews including detailed assessment of current alcohol consumption and DSM-IV dementia diagnoses. Associations between alcohol consumption (in grams of ethanol), type of alcohol (wine, beer, mixed alcohol beverages) and incident dementia were examined using Cox proportional hazard models, controlling for several confounders.

Results: incident overall dementia occurred in 217 of 3,202 participants over a mean follow-up period of 3 years. Significant relationships were found between alcohol consumption (prevalence at baseline: 50.0%) and incident overall dementia (adjusted hazard ratio (HR) 0.71, 95% CI 0.53–0.96), respectively, incident Alzheimer dementia (adjusted HR 0.58, 95% CI 0.38–0.89).  With regard to quantity of alcohol and type of alcohol, all hazard ratios were found to be lower than 1.

Conclusion: in agreement with meta-analyses that include younger age groups, our study suggests that light-to-moderate alcohol consumption is inversely related to incident dementia, also among individuals aged 75 years and older.

Forum Comments

Background:  In the last 31 years (1980 – 2011) the association between moderate alcohol intake and cognitive function has been investigated in 71 studies comprising 153,856 men and women from various populations with various drinking patterns.  Most studies showed an association between light to moderate alcohol consumption and better cognitive function and reduced risk of dementia, including vascular dementia and Alzheimer dementia.

Comments on the present study:  This new study from Germany is well done and has some interesting features:

•  a large sample size of 3,202 men and women with a mean age of 80.2 years.
•  participants recruited from general practice (probably reducing selection bias)
•  a thorough baseline examination and almost complete follow up
•  a large number of non-drinkers and moderate drinkers
•  substantial incidence rates of dementia during the follow-up period of 3 years
•  ascertainment of dementia even among subjects who died during follow up.

As stated by Forum member Erik Skovenborg, “The association found between alcohol consumption and incident overall dementia [adjusted hazard ratio (HR) 0.71, 95% CI 0.53-0.96], respectively, incident Alzheimer dementia (adjusted HR 0.58, 95% CI 0.38-0.89) are in accordance with most other studies, including the large Rotterdam Study1 and The Cardiovascular Health Study.2 Since a randomized, controlled study of alcohol consumption and risk of dementia has not been done (and would not be feasible), the jury is still out concerning the importance of confounding.  Persons who continue drinking alcohol throughout old age are the remainder population, as mentioned by the authors of this study, exhibiting a survivor phenomenon.  Happy people with many friends have the most opportunities for social drinking, and in this study alcohol consumption was significantly associated with factors that are protective for the development of dementia: better education, not living alone, and absence of depression.  However, even after controlling for these and several other factors, the risk for incident dementia was still significantly lower among light-to-moderate alcohol consumers.  Even so it may still be a part of the explanation that old German men and women, who drank alcohol sensibly in old age, also have a healthier lifestyle in terms of physical, dietary, and mental perspectives.”

Forum member Roger Corder adds: “From all I have read on this subject, I fully agree that it is very difficult to separate alcohol consumption from other healthy lifestyle factors in populations where moderate drinking is commonplace.  In this respect, the study doesn’t correct for a healthy diet, which is also likely very important, as a poor diet is associated with increased risk of dementia due to deficiencies such as low omega-3 fat intake, inadequate vitamin B12, etc.  However, it is also known that improved vascular function in alcohol drinkers could account for some element of reduced dementia risk.”

Forum member David Vazour comments: “Mechanistically speaking, I don’t think that the antioxidant capacity of wine phenolics would be the only explanation for these findings.  First of all, following absorption these compounds are readily bio-transformed, therefore decreasing their antioxidant potential.  There is also the question of whether or not they are able to cross the blood brain barrier and act in situ.  Knowing the concentration of antioxidant enzymes and molecules within brain tissue, it is almost impossible to provide protection through only an antioxidant mechanism.  Anti-inflammatory and vascular?  Maybe.  Further, wines vary in their phenolic composition (due to type of grape, climate, soil variations, etc.).  It would be interesting to re-analyze the results based on phenolic composition.”

Other Forum reviewers thought this was a well-performed study, with a result supporting previous ones, but there were limitations to the study.  It included ex-drinkers with never drinkers in the referent group; there was a rather short period of follow up; among subjects reporting “mixed” types of beverage intake (that had the greatest estimated effect), numbers of subjects according to the percentage of their total alcohol intake from wine (e.g., <30%, ≥ 30%) were not given; there was no evidence of a dose-response curve, probably due to small numbers; the small numbers also probably made it impossible to assess for differences in effect for Alzheimer dementia and for other dementias.  A Forum member added: “My only complaint is that it is a bit surprising to still see in 2011 analyses of all stroke considered as one group.  The authors do discuss the disparate relations of alcohol drinking to ischemic and hemorrhagic stroke, a fact that makes it imperative to consider them separately.”

A German Forum member, Ulrich Keil, stated: “The Swiss physician and philosopher Paracelsus (1493-1541) wrote: “Alle Dinge sind Gift, und nichts ist ohne Gift. Allein die Dosis macht, dass ein Ding kein Gift ist.”  (An approximate English translation is “All things are poison, and nothing is without poison.  However it is the dose that makes a thing not a poison.”)  The subjects in this study were in general very moderate drinkers.

An American reviewer, Harvey Finkel, added: “The badge of age is not a warning label of fragility.  While, I believe, one should not start to drink just because one has attained seniority, neither must one stop!  Elderly folks handle alcohol with more responsibility than do the young, and they may derive greater health benefits from moderate drinking.  Age is not a reason for abstinence.”

Professor Finkel continued: “A long-ago physycke doctor, Andrew Boorde, noted, ‘Wine…moderately drunken, it doth quicken a man’s wits….’  Such expressions of folk wisdom have been repeatedly confirmed and refined scientifically in the modern era.”  Professor Finkel ends with the following:

“What though youth gave love and roses,
Age still leaves us friends and wine.
Thomas Moore”

References from Forum comments

1.  Ruitenberg A, van Swieten JC, Witteman JC, et al.  Alcohol consumption and risk of dementia: the Rotterdam Study.  Lancet 2002;359:281-286.

2.  Mukamal KJ, Kuller LH, Fitzpatrick AL, et al.  Prospective study of alcohol consumption and risk of dementia in older adults.  JAMA 2003;289:1405-1413.

Forum Summary:  A population-based study of elderly Germans, aged 75 and older, evaluated the association between alcohol consumption and incident overall dementia and Alzheimer dementia over 3 years.  There was good ascertainment of the development of dementia, even among subjects who died during follow up.

Of 3,202 subjects free of dementia at baseline, 217 subjects met criteria for dementia during follow up.  Subjects consuming alcohol had approximately 30% less overall dementia and 40% less Alzheimer dementia than did non-drinking subjects.  Unlike many previous studies, no significant differences were seen according to the type of alcoholic beverage consumed.  Overall, these results are similar to several previous studies in the very elderly and suggest that moderate drinking is associated with less dementia, even among individuals aged 75 years and older.

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Contributions to this critique by the International Scientific Forum on Alcohol Research were made by the following members:

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA

Roger Corder, PhD, MRPharmS, William Harvey Research Institute, Queen Mary University of London, UK

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Ulrich Keil, MD, PhD, Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany

David Vauzour, PhD, Dept. of Food and Nutritional Sciences, The University of Reading, UK