Critique 008: Alcohol, Tobacco, Alzheimer’s

Critique 008                                                                                                                 13 June 2010

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García AM, Ramón-Bou N, Porta M.   Isolated and joint effects of tobacco and alcohol consumption on risk of Alzheimer’s Disease.   Journal of Alzheimer’s Disease 2010;20:577–586.  (DOI 10.3233/JAD-2010-1399).

Authors’ Abstract

The roles of smoking and alcohol on the development of Alzheimer’s disease (AD) remain unclear.  The authors performed a case-control study on the effects of both exposures before the age of onset of the disease in the cases (and same reference age for their age-matched controls) on disease risk.  Interviews were conducted with population controls (n = 246) and relatives of cases (n = 176) identified through local Alzheimer’s Disease Associations.  Logistic regression models were built adjusting by gender, age, residence, education, economic situation, employment, and history of dementia in close relatives.  

Risk of AD was unaffected by any measure of tobacco consumption.  Alcohol consumers showed a lower risk of AD than never consumers (adjusted odds ratio, OR = 0.53, 95% CI 0.32, 0.88), with differences by gender (women OR = 0.48, 95% CI 0.27, 0.84; men OR = 0.80, 95% CI 0.23, 2.80).  Mean daily total consumption of alcohol and time consuming alcohol showed increasingly protective dose-response relationships in women.  Lower AD risk was observed in alcohol drinkers of both genders who never smoked (OR = 0.37, 95% CI 0.21, 0.65).  All of these associations were independent of the presence of apolipoprotein E4 allele(s) in the cases.  

Although the sample was small for some analyses addressing these interactions, our results suggest a protective effect of alcohol consumption, mostly in non-smokers, and the need to consider interactions between tobacco and alcohol consumption, as well as interactions with gender, when assessing the effects of smoking and/or drinking on the risk of AD.

Forum Comments

A number of papers in recent years have suggested that moderate drinking is associated with lower risk of AD, including the key early reports from the PAQUID study in France.¹  The present study was not large, but it tends to support findings of many previous reports.  It is unfortunate that there was no access to patient’s notes or ability to confirm the diagnosis of AD by the authors, forcing them to obtain data on age at diagnosis, symptoms, etc., from caregivers.  There was limited ability to judge whether the subject had AD or other types of dementia.  Also, having to use caretakers to describe previous drinking may have decreased the accuracy of estimates of alcohol intake prior to the diagnosis of AD.

The number of subjects was generally inadequate to judge for interactions between alcohol and tobacco use or other factors, although there were reasonable numbers for the overall conclusions: 176 people in the demented population and 246 in the control.  It is of note that the control population started with 753 invitation letters and the demented with 268; it is possible that the differing response rates introduced bias.  However the major difference between the two samples was that individuals in the control group were personally interviewed whereas, of necessity, the next of kin of the demented participants were the interviewees, as this was a case-control study. This does introduce the potential for differing recall of past behavior between the two groups.  

The decrease in AD for moderate drinkers in this study was seen primarily among women and non-smokers; reasons for these differences are not know.  (Surprisingly, fewer than 25% of the subjects in this study were smokers, mainly because smoking was very unusual among older women in Spain at the time of this study.)  Unlike what has been shown in several previous studies, the authors state that “no major differences were found among the three types of alcohol consumed (beer, wine, and liquors),” but do not present their results. 

General comments on alcohol and Alzheimer’s Disease

Alzheimer’s disease is an irreversible and progressive brain disease that slowly destroys memory and thinking skills, and is the most common cause of dementia among older people.  Although it is not known how the Alzheimer’s disease process is initiated, damage to the brain begins quietly over many years before problems are evident.  The pathology of AD includes tangled bundles of nerve fibers (neurofibrillary tangles) and amyloid plaques that are seen to form in deep brain tissue.  The loss of neuronal connections in the brain is another common pathophysiologic consequence of AD.  Significant memory and functional loss is associated with widespread brain changes involving the hippocampus and also include contraction and shrinkage of brain mass.

It is suspected that the causes of AD include genetic, environmental, and lifestyle factors.  Its occurrence is more common among people with lower levels of education, those with a history of head trauma, and people with a familial occurrence of the disease, but few lifestyle habits seem to affect its incidence.  Some data suggest that a nutritious diet, physical activity, social engagement, and mentally stimulating pursuits are associated with a lower risk of AD.  The association between cognitive decline and vascular and metabolic conditions such as heart disease, stroke, high blood pressure, diabetes, and obesity is of interest, and may suggest common mechanisms (as moderate alcohol intake has been shown to be associated with lower risk of heart disease and diabetes).  This study suggests that alcohol may have a protective effect against AD.

Tobacco use, a profound risk factor for vascular disease, had no effect on AD in the present study.  (Some other studies have suggested that smoking is associated with lower risk of AD, and the authors of the present study propose some mechanistic explanations for such an effect.)  Further investigation of the effects of these and other lifestyle factors on the risk of AD is warranted and may provide essential information to protect the mental and general health of the elderly.

While this study suggests some protection from moderate drinking, there is always the possibility that the results may relate to residual confounding, as moderate drinkers tend to be better educated and have other healthy lifestyle factors.  Thus, there is a need for considerable more research to determine the true association between alcohol intake and the development of dementia.

Reference from Critique

1.  Orgogozo JM, et al.  Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area.  Rev Neurol (Paris) 1997;153:185-192.

Summary

In a case-control study from Spain on the effects of smoking and alcohol use on the risk of Alzheimer’s Disease (AD), the authors found that the risk of AD was unaffected by any measure of tobacco consumption.  On the other hand, alcohol consumers showed a 47% lower risk of AD than never consumers, with effects mainly among women and among never smokers.  No differences were noted by type of alcoholic beverage consumed.  The authors conclude that mean daily total consumption of alcohol showed increasingly protective dose-response relationships in women.

The numbers in this analysis were rather small for the evaluation of potential interactions between alcohol and many factors, and there is always the possibility of residual confounding by associated lifestyle behaviors.  Still, the study supports a number of previous epidemiologic studies showing lower risk of developing AD for moderate consumers of alcohol.

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

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

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

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

Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona, USA

Dominique Lanzmann-Petithory,MD, PhD, Nutrition/Cardiology, Praticien Hospitalier Hôpital Emile Roux, Paris, France

Ross McCormick PhD, MSC, MBChB, Associate Dean, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

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

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