From the International Centre for Health and Society, Department of Epidemiology and Public Health, University College London, London, United Kingdom.
Received for publication June 26, 2003; accepted for publication February 27, 2004.
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ABSTRACT |
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alcohol drinking; cognition; cohort studies; men; middle aged; women
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INTRODUCTION |
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Many questions remain. Most existing studies are based on older cohorts, and it is unclear whether a possible protective effect on cognitive function extends to younger, healthier cohorts. It has previously been shown that benefit was confined to those with evidence of cardiovascular disease and diabetes (10). The precise nature of exposure to alcohol remains unclear. It is not known whether pattern of drinking is important, as well as average volume consumed (2, 5), and whether effects are similar in cross-sectional and longitudinal analyses (11). Most existing studies analyses used nondrinkers as the comparison group. Doing so may confuse the interpretation because nondrinkers, in particular former drinkers, are usually different from drinkers in other, prognostically important ways. It is better to categorize drinking into several levels and use one of these groups as the reference.
Several possible mechanisms might explain an association between alcohol consumption and cognitive function. For example, moderate consumption may be a proxy marker for good mental and physical health and for high socioeconomic position, both of which are related to good cognitive performance (12, 13). Alternatively, alcohol may have a causal effect via improved vascular function, which is itself associated with good cognitive ability in the general population (1416).
The objective of the present study was to test whether alcohol consumption (both average volume consumed and frequency of drinking) was associated with cognitive function in a sample of middle-aged adults. We were able to explore whether cross-sectional relations differed from longitudinal analyses (mean follow-up: 11 years) and whether changes in drinking behavior influenced any association. The Whitehall II Study offers an important opportunity to explore several possible explanations, with its repeated measures of alcohol consumption, measures of social position, physical and mental health tests, and a comprehensive battery of cognitive function tests.
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MATERIALS AND METHODS |
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Alcohol consumption
At baseline and subsequent study phases, participants were asked to report the number of alcoholic drinks they had consumed in the last 7 days. This information was divided into "measures" of spirits, "glasses" of wine, and "pints" of beer. In the United Kingdom, a standard measure of spirits and a glass of wine are considered to contain 8 g of alcohol, while a pint of beer contains 16 g of alcohol. Participants were also asked to report the frequency of their drinking over the last 12 months by circling one of six specified options (twice a day or more, almost daily, once or twice a week, once or twice a month, special occasions only, none).
Tests of cognitive function
The cognitive test battery consisted of five standard tasks chosen to comprehensively evaluate cognitive functioning in middle-aged adults. The choice of this battery rather than a specific test for dementia was guided by an attempt to capture the entire range of cognitive ability and not be restricted by ceiling effects in this middle-aged cohort. The battery was composed of the following tests. The first was a 20-word free-recall test of short-term memory. Participants were presented with a list of 20 one- or two-syllable words at 2-second intervals and were then asked to recall in writing as many of the words as they could, in any order; they had 2 minutes to do so. The AH4 (18) is composed of a series of 65 verbal and mathematical reasoning items of increasing difficulty. This test of inductive reasoning measures the ability to identify patterns and infer principles and rules. Participants had 10 minutes to complete this section. The Mill Hill vocabulary test (19) assesses knowledge of verbal meaning and encompasses the ability to recognize and comprehend words. We used this test in its multiple format, which consists of a list of 33 stimulus words ordered by increasing difficulty and six response choices. Finally, we used two measures of verbal fluency: phonemic and semantic. Phonemic fluency was assessed via "s" words and semantic fluency via "animal" words. Subjects were asked to recall in writing as many words beginning with "s" and as many animal names as they could. One minute was allowed for each test.
Possible confounders and mediators measured at baseline
Age and smoking status
Participants were asked to report whether they currently smoked (cigarettes, hand-rolled tobacco, or cigars), the number of items they smoked per day, or when they stopped smoking.
Socioeconomic position
On the basis of salary and work role, the civil service defines a hierarchy of employment grades ranging from senior executive officers to clerical and support staff. This measure was used to control for socioeconomic position in the analyses.
Mental health
The 30-item standard General Health Questionnaire was used as an indicator of mental health (20).
Physical Component Score
The Short Form-36 General Health Survey is a 36-item questionnaire that covers issues relating to physical, psychological, and social functioning (21). It is coded into eight scales: physical functioning, social functioning, role limitations due to physical problems, role limitations due to emotional problems, vitality, bodily pain, general health perception, and general mental health. These eight scales can be summarized into physical and mental components scores by using factor analysis (22, 23); in this study, we used the Physical Component Score as a measure of general physical functioning. A low score implies poor functioning, with 50 being the mean in the general US population (possible score range: 0100).
Vascular risk factors
A Hawksley random-zero sphygmomanometer (Hawksley, Lancing, Sussex, United Kingdom) was used to measure blood pressure twice, with the subject in the sitting position after 5 minutes of rest. Serum cholesterol was determined by the cholesterol oxidate peroxidase colorimetric method (BCLkit; Boehringer, Mannheim, Germany).
Cardiovascular disease and diabetes during follow-up
Potential cases of angina and myocardial infarction arose from positive responses to self-completed questions on symptoms of chest pain (24), physician diagnoses of angina or myocardial infarction, cardiac investigative items (exercise electrocardiography and angiography), and treatments (nitrate medications and revascularizations). Twelve-lead resting electrocardiograms (Siemens Mingorec, Siemens Medical Solutions, Erlington, Germany) were performed in the screening clinic. To identify a group with evidence of cardiovascular disease, we used an inclusive measure of coronary heart disease (including abnormal resting electrocardiogram, angina, and myocardial infarction). Cases of intermittent claudication, stroke, and diabetes were obtained from recall of a physicians diagnosis.
Statistical methods
The risk of poor cognitive performance associated with alcohol consumption was estimated by using binary logistic regression analyses. For each test, poor cognitive function was indicated by inclusion in the worst quintile. Analyses were carried out separately for men and women to explore possible effect modification by gender, and all analyses were controlled for age and smoking.
Both average volume of alcohol consumed per week and reported frequency of drinking were considered. The reference group was set as those who reported drinking in the last year but not in the past week. These participants were chosen in preference to lifetime abstainers or former drinkers, who typically have worse health profiles than drinkers do.
We compared analyses in which current drinking (cross-sectional analyses) and drinking reported at baseline (longitudinal analyses) were used. In a sensitivity analysis, those who changed their consumption between phases 1 and 5 were excluded. Finally, the analyses were repeated among a cohort that excluded those participants with evidence of cardiovascular disease/diabetes during follow-up.
The General Health Questionnaire, Physical Component Score, and employment grade (measured at baseline) were included in the regression as possible confounders. The mediating roles of total blood cholesterol and of systolic and diastolic blood pressure were also explored by entering these variables into the model.
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RESULTS |
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Adjusting for smoking and age only showed that the lowest odds ratios were found for those drinking almost daily and twice a day or more compared with those who drank only on special occasions (table 4). Never drinkers were more likely to be in the lowest quintiles of cognitive function. Additional adjustments for physical and mental health and for employment grade weakened these associations.
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DISCUSSION |
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Some previous studies have reported a U-shaped relation, suggesting that drinking larger quantities of alcohol is associated with worse cognitive function (25). Kalmijn et al. (4) reported that the most benefit was found for those consuming between one and four drinks per day, while Zuccala et al. (3) reported a nadir of 0.5 liters of wine per day for women and 1 liter per day for men. The Whitehall II cohort included relatively few heavier drinkers, and it was therefore not possible to explore the upper limits of the possible benefit attributable to alcohol. In terms of cognitive function, we found that frequent drinking may be more beneficial than drinking only on special occasions. This finding is compatible with those from the few previous studies that explored drinking patterns and cognitive function (11).
Several possible mechanisms might explain the relation between alcohol consumption and improved cognitive function. First, the association may be mediated by confounding factors, such as good physical and mental health or social position. We did find some evidence for the role of social position, and there may still be confounding by other factors, for example, engaging in leisure activities that maintain cognitive function (2527). Our results appear to suggest some specificity in the association between alcohol consumption and cognitive ability. After adjustment for the confounders, we found that alcohol had no statistically significant beneficial impact on memory. However, results of the Mill Hill test, which measures crystallized intelligence, showed an association with alcohol for both men and women. Crystallized intelligence measures accumulated information and vocabulary; thus, the association with alcohol consumption could have been due to residual confounding by social factors. However, the association with the fluency measures implicates other pathways. Verbal fluency (both phonemic and semantic) is a measure of executive function or a "meta" cognitive ability integrating other cognitive processes such as attention and speed of information processing (2830). Our results suggest an association between volume of alcohol consumed and executive function.
Second, the association may be causal. It is well recognized that alcohol is related to reduced levels of cardiovascular disease and atherosclerosis, mediated by beneficial effects on lipid levels, lipoprotein(a) levels, insulin sensitivity, fibrinogen levels and fibrinolytic activity, and platelet function. Alcohol also reduces the risk of cerebral arterial occlusion and increased cerebral blood flow, which improves cognitive function (4). We previously showed in this cohort that the presence of vascular disease was associated with diminished cognitive function (16). Launer et al. (10) reported that the beneficial effects of alcohol on cognitive function were restricted to only those with existing cardiovascular disease or diabetes. Compared with abstainers, persons drinking one or two glasses of alcohol per day had a significantly lower risk of poor cognitive function. In our study, excluding those with a history of cardiovascular disease or diabetes did not attenuate the associations with alcohol consumption and cognition. However, these diseases do not fully reflect subclinical atherosclerosis and small-vessel disease in the brain, which may be a stronger intermediate factor.
Stronger protective effects of alcohol consumption on cognitive function in women have been reported before (1, 4, 6). The mechanisms behind this stronger association remain unclear. It is possible that the explanation is biologic, linked to sex differences in alcohol metabolism (31, 32). The gender differences may operate through body weight, tissue saturation, stomach enzymes, and the proportion of fat to water in the body. It is also possible that the sociocultural patterns of drinking behavior and beverage choice differ for men and women, but, unfortunately, we were unable to look at these effects with our data.
The objective of this study was to examine the association between cognition and alcohol consumption among persons who were younger and consequently healthier than those examined previously. The study design (involving responding to a long questionnaire and traveling to a screening clinic for the medical examination), age of the respondents, and the question on long-standing illness make it likely that this association was examined in a group free of dementia. The findings from this large study provide evidence of the benefits of alcohol consumption on cognitive function for relatively young men and women. This evidence was found in both longitudinal (11 years of follow-up) and cross-sectional analyses, and, with the repeated measures of alcohol consumption, we were able to exclude those who had changed their consumption levels during follow-up. A battery of cognitive tests was used to examine this association, because a test used to screen for dementia (e.g., the Mini-Mental State Examination) would have resulted in little variability in the cognitive scores because of ceiling effects. The disadvantage with the tests used is the lack of standard criteria to judge poor cognitive performance. In keeping with other research in this area, we present analysis in which the worst quintile was used to denote poor performance (33). However, the association between alcohol consumption and cognition was similar when continuous measures of both variables were used (results not shown but available from the authors).
The analysis presented in the paper used very light drinkers as the reference group, in preference to abstainers, so that the comparison groups were similar regarding other characteristics. In addition, we were also able to control for the possible confounding factors of physical and mental health and of social position in the analyses. Further research is required to examine the relation between alcohol consumption and cognitive decline, both normative age-related and dementia-related decline. Unfortunately, we do not yet have repeat measures of cognitive function and were not able to look at decline. Previous research found that decline in function was slower among drinkers than abstainers (9, 11), while others found no relation (7, 10).
In addition to the cognitive benefits reported here, moderate levels of alcohol consumption have a protective effect against coronary heart disease (34) and possibly ischemic stroke (35). However, the benefits of alcohol drinking may be outweighed by an increased risk of other diseases (including cirrhosis of the liver, pancreatitis, upper aerodigestive cancers, and alcohol psychoses) and of violence and accidents. The balance of risk and benefits is different for different sections of society (36), and it is not proposed that the findings from this and other studies be used to encourage increased consumption.
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NOTES |
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REFERENCES |
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