Alcohol Intake and Risk of Dementia

Jose A. Luchsinger, MD; Ming-Xin Tang, PhD; Maliha Siddiqui, MPH; Steven Shea, MD; Richard Mayeux, MD

Disclosures

J Am Geriatr Soc. 2004;52(4) 

In This Article

Discussion

This study showed that, in a cohort of individuals aged 65 years and older, light to moderate alcohol intake was associated with a lower risk of dementia and AD, whereas intake of beer and liquor was not associated with incident dementia. Analyses examining total alcohol intake also indicated that light or moderate intake was not associated with a lower risk of dementia or AD. Analyses stratified by the presence of APOE-ε4 also showed that the association between light wine intake and lower risk of AD was restricted to individuals without the APOE-ε4 allele, whereas in individuals who were heterozygous or homozygous for the allele, there was no association between wine intake and lower risk of AD.

Moderate alcohol intake has been found to be associated with a decreased risk of coronary disease[22,23,24] and ischemic stroke[11] in observational studies. On this basis, it would be expected that moderate alcohol intake would be associated with a lower risk of vascular dementia, defined in the current study as DAS. Furthermore, the role of cerebrovascular disease in the development of AD is unclear, but if cerebrovascular disease is a precipitant of AD, moderate alcohol intake could also be expected to decrease the risk of AD. Another mechanism through which alcohol would be expected to decrease the risk of AD would be through antioxidant mechanisms. Studies have shown that oxidation has an important role in AD,[25] and there is ongoing research on the primary prevention of AD with antioxidant vitamins. Alcohol has antioxidant effects,[26,27] and wine in particular has been found to have important antioxidant effects. One recent report from the Rotterdam study found, in individuals aged 55 and older, that light to moderate drinking of alcohol (1-3 drinks per day) was associated with a lower risk of dementia and that this effect was not particularly limited to any beverage type.[2] A study from the Bordeaux region of France in individuals aged 65 and older reported that moderate wine consumption (3-4 glasses a day) was associated with a lower risk of AD and overall dementia, whereas mild consumption (1-2 glasses a day) was associated with a lower risk of AD but not dementia.[3] Individuals in this study drank wine almost exclusively. The Canadian Study of Health and Aging also reported a lower risk of AD with consumption of wine but not other alcoholic beverages.[28] The Copenhagen City Heart Study recently reported in a nested case control study that monthly and weekly intake of wine was associated with a decreased risk of dementia in individuals aged 65 and older, whereas intake of alcohol was not associated with a decreased risk of dementia.[5] Other smaller studies have found no association between alcohol intake and a lower risk of cognitive impairment or dementia.[29,30,31] The findings of the current study are consistent with the latter two studies, but as opposed to the Rotterdam study, no association was found between intake of beer and liquor and dementia. The statistical power to detect an association between intake of more than three servings of daily alcohol was limited, but the results seem to indicate an association with a higher risk of dementia, consistent with previous findings.[14]

There were few moderate drinkers in the study, and the light and moderate intake categories were aggregated; thus, light intake of alcoholic beverages (1 serving a month to 6 servings a week) mostly affected the results reported for light to moderate intake. For example, 152 individuals reported light intake of wine, and 11 individuals reported moderate intake of wine. The adjusted HR of AD was 0.69 (95% CI= 0.44-1.09; P = .065) for light intake of wine and 0.77 (95% CI= 0.12-5.62; P = .540) for moderate intake of wine. Thus, the results for light to moderate intake of wine mostly reflect the association between light intake and AD; the HR for moderate intake was in the same direction as for light intake, but this needs to be explored in a larger sample.

There are several potential explanations for the finding of a differential association between beverage type and incident dementia. Wine has two potential beneficial effects; one is through alcohol itself, and the other through substances with antioxidant effects in plasma, such as polyphenols.[26,27] Alcohol has a beneficial effect on vascular biology through increased levels of high-density lipoprotein, decreased platelet adhesiveness, and improved endothelial function that probably explains the association between moderate alcohol intake and cardiovascular outcomes,[32] irrespective of type of alcoholic beverage; the finding of a nonsignificant association between moderate alcohol intake and lower incidence of DAS is consistent with this explanation. Processes that originate, modulate, or precipitate the deposition of amyloid beta in the brain,[33] such as oxidative stress, rather than vascular processes, may better explain the development of AD, and the vascular effects of the alcohol component of alcoholic beverages may not be enough to cause an association between moderate intake of any alcoholic beverage and AD. The presence in wine of nonalcoholic components such as particular antioxidants could explain a differential effect of wine on AD. For example, liquor has been shown to have less antioxidant activity than wine.[34] Another potential explanation for this finding is that of residual confounding. Drinkers of wine had more years of education than liquor or beer drinkers. It is possible that the study did not adjust properly for education and that residual confounding by educational attainment resulted in the association between light wine consumption and lower risk of AD. A third possibility is that of uncontrolled confounding. It is possible that other behavioral characteristics that are associated with a lower risk of AD, that are unknown, and that were not accounted for in the statistical models accompany wine drinking. Also, drinkers of wine may have patterns of alcohol intake that are different than those of beer andliquor drinkers. For example, drinkers of wine may consume mostly light to moderate amounts of alcohol, whereas liquor and beer drinkers consume amounts of alcohol deemed to be unhealthy in shorter periods of time; because average intake was measured, these patterns cannot be taken into account. These data have differences from those from the previously reported studies that may limit comparisons. The report from the Rotterdam Study examined a cohort that was younger than this one (≥ 55 compared with ≥ 65),[2] and therefore the two studies may be measuring different cumulative intakes that are reflected in the results. Furthermore, the latency phase of dementia may be at significantly different stages in the two studies given the age difference, and the effect of any exposure on dementia may be different in the cohorts. The Bordeaux study had a cohort similar to the one in the current study in terms of age, but wine was the only beverage studied. The Copenhagen City Heart Study is similar in age structure to the current one and found similar results, but alcohol intake was measured 15 years before the selection of cases and controls. Lastly, there may be significant cultural differences between Europe and the United States in terms of alcohol intake that may also make this study not comparable with European studies. In the Rotterdam study, only 21% of individuals reported no alcohol consumption, whereas 70% of individuals in the current study reported no alcohol consumption.

The stratified analyses revealed that wine was not associated with a decreased risk of AD in individuals homozygous or heterozygous for APOE-ε4, whereas there was a decreased risk for individuals without the allele. APOE-ε4 is a predictor of the development of AD.[35] Findings from another study relating moderate alcohol intake to a decreased risk of cognitive decline in individuals without the APOE-ε4 allele support these results.[36] The mechanism for the effect of APOE-ε4 on the risk of AD is not clear, but it probably involves an increase in the deposition of amyloid β in the brain.[35] One possible explanation is that the presence of APOE-ε4 increases the risk of AD in such a way that it overwhelms the potential protective mechanism of wine. For example, if wine were to have an antioxidant effect in relation to AD pathogenesis, then wine would not be protective in individuals who have the highest disease burden. One study reported a decreased risk of cognitive function associated with alcohol intake in individuals with diabetes mellitus and cardiovascular disease,[37] but this was not replicated in the current study in stratified analyses by diabetes mellitus or cardiovascular disease.

This study has several strengths. Individuals with very mild forms of dementia that might be considered cognitive impairment without dementia (CDR.= 0.5) were excluded, thus minimizing the risk of including individuals with preclinical dementia whose alcohol intake was a result of behavior modification related to the outcome. Standard measures of the exposure and the outcome were also used.

The main limitation of this study is common to most studies of diet and disease, namely misclassification of the exposure. The coefficient relating report of alcohol to food records showed a moderate correlation, indicating some misclassification in the report of alcohol intake. Also, it was assumed that alcohol intake was stable over time, but it is probable that there was significant intraperson variation in alcohol intake that was not taken into account. Assuming nondifferential misclassification of alcohol intake, this would result in underestimation of the association between alcohol intake and incident dementia. Another limitation of the study is that its primary focus was the detection of memory-based cognitive impairment and distinguishing between AD and DAS; thus, it is possible that cases of dementia not caused by AD or DAS were missed or that other causes of dementia were misclassified primarily as AD.[38] It is important to point out that this study and others showing similar results are observational and that, given the potential risks associated with alcohol intake, no recommendations on alcohol intake should be based on these results. Furthermore, if the association in this study represented a true protective effect, it is possible that the risk of dementia is decreased at the expense of increasing other comorbidities, including forms of cognitive impairment, and this cannot be addressed with these data.

In conclusion, it was found that light to moderate intake of wine was associated with a decreased risk of dementia and Alzheimer's disease in individuals without the APOE-ε4 allele. Similar intakes of beer, liquor, or total alcohol were not related to a decreased risk of Alzheimer's disease.


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