SEX DIFFERENCES IN SPATIAL VISUALIZATION AND EPISODIC MEMORY AS A FUNCTION OF ALCOHOL CONSUMPTION

J. E. YONKER1,*, L.-G. NILSSON2, AGNETA HERLITZ2,3 and R. M. ANTHENELLI4,5,6

1 University of Cincinnati, Raymond Walters College, Cincinnati, OH, USA, 2 Stockholm University, Stockholm, 3 ARC-Division of Geriatric Epidemiology, Neurotec, Karolinska Institute, Stockholm, Sweden, 4 Tri-State Tobacco and Alcohol Research Center, Cincinnati, OH, USA, 5 Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA and 6 Department of Psychiatry, University of Cincinnati Medical School, Cincinnati, OH, USA

* Author to whom correspondence should be addressed at: Behavior Sciences Department, Raymond Walters College, University of Cincinnati, Muntz Hall, 9555 Plainfield Rd, Cincinnati, OH 45236, USA. Tel.: +1 513 936 7120 (ext.) 3266; Fax: +1 513 745 5780; E-mail: julie.yonker{at}uc.edu

(Received 13 August 2004; first review notified 13 October 2004; in revised form 8 November 2004; accepted 4 January 2005; Advance Access publication 29 March 2005)


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Aims: Sex differences in visuospatial ability as well as episodic memory have been reliably demonstrated, irrespective of alcoholism. Studies in alcoholics have consistently documented cognitive deficits in visuospatial ability, problem solving and memory function. This cross-sectional, population-based study examined if sex differences in cognitive performance could be impacted by alcohol consumption. Methods: Drinking data were collected from 2224 randomly sampled adults, aged between 35 and 85 years, who participated in the Betula study on memory, health and aging. Participants were classified into non-, light, moderate and heavy drinking subgroups based on sex-adjusted normative values. Cognitive tasks demonstrating clear sex differences, such as episodic memory tasks (favouring women) and spatial visualization tasks (favouring men), were conducted and performance was assessed by sex and the drinking group. Results: After controlling for age and education, overall analyses found expected sex differences in episodic memory and spatial visualization that were apparent across the entire population. When these sex differences were examined by drinking group, visuospatial performance favouring men disappeared for the moderate to heavy drinking groups, but higher performance by women on episodic memory tasks was consistent across all levels of alcohol consumption. Traditional biomarkers of increased alcohol consumption (GGT and MCV) correlated with the reported drinks/day. Conclusions: These results lend support to the theory that moderate alcohol intake may be beneficial to cognitive function in women, but not necessarily in men.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Evidence has been mounting that the association between cognitive abilities and alcohol consumption is sex dependent (Dufouil et al., 1997Go; Elias et al., 1999Go). Sex differences have been well established in several cognitive domains (Halpern, 1997Go), irrespective of alcohol consumption. Men typically excel in spatially oriented tasks, whereas women usually have a better episodic memory (Yonker et al., 2003Go). Although social and cultural explanations for the observed sex differences have been postulated, evidence also suggests that fluctuating sex hormone levels could have an impact (Yonker et al., 2003Go). Sex differences in alcohol metabolism and the interactions among sex hormones and neurotransmitters involved in cognitive processing suggest a possible explanation for the observed differences between alcohol consumption and cognitive functioning among men and women (Dufouil et al., 1997Go).

Alcohol-related cognitive deficits have been found in a variety of cognitive spheres (Nixon et al., 1998Go) and replicated throughout different cultures (Mann et al., 1999Go). Most of this work, however, has been done in male alcoholics who have shown deficits in cognitive efficiency, problem solving, verbal and non-verbal abstractions, visuospatial ability, learning and memory (Parsons, 1998Go). The connection between alcohol intake and cognitive function in non-clinical samples remains unclear. Some studies report no significant association between social drinking and the level of cognitive function (Carey and Maisto, 1987Go; Dent et al., 1997Go) and others report that increasing alcohol consumption was related to an enhanced cognitive task performance (Bates and Tracy, 1990Go; Christian et al., 1995Go; Launer et al., 1996Go). Still other investigators report a U- or J-shaped, curvilinear relationship between alcohol consumption and cognitive function, with low to moderate drinkers performing better than both abstainers and heavy drinkers (Herbert et al., 1993Go; Hendrie et al., 1996Go). While the literature on chronic, habitual social drinking is growing, few clear-cut results have emerged on how low or moderate amounts of alcohol can produce changes in the human brain that result in an overt cognitive behaviour (Eckardt et al., 1998Go).

Despite the fact that most of the early work on alcohol consumption has been conducted on men or mixed gender groups, it is particularly important to examine the data for men and women separately. Women typically consume alcohol less frequently and in smaller amounts than men (Dufouil et al., 1997Go; Elias et al., 1999Go). The lower average body water content in women is associated with higher peak blood alcohol levels compared with men (Graham et al., 1998Go). Sex differences have been reported with respect to the effects of alcohol on brain structure; alcoholic men show deficits in gray and white matter volume with an enlargement of the ventricles compared with non-alcoholic men, but alcoholic women have no detectable deficits in these brain areas when compared with healthy women (Pfefferbaum et al., 2001Go). Furthermore, brain metabolism in alcoholic women revealed lower levels of N-acetylaspartate compared with non-alcoholic women; however, there were no differences in the levels of this metabolite between alcoholic and non-alcoholic men (Schweinsburg et al., 2003Go). Investigations related to alcohol and cognition in women seem to suggest that alcohol may have a beneficial effect on the cognitive function of women (Dufouil et al., 1997Go; Elias et al., 1999Go). In a large French longitudinal study of older adults, Dufouil et al. (1997)Go found that the general cognitive test scores were not associated with the self-reported alcohol consumption in men; however, among women, moderate alcohol consumption (>2 drinks/day) was associated with a better performance on the majority of cognitive tasks. Similarly, Elias et al. (1999)Go used the Framingham heart study database to demonstrate that women who reported drinking moderately (2–4 drinks/day) performed at a higher level on a variety of cognitive tasks when compared with the abstainers. They also found a smaller, more limited, positive relationship at higher drinking levels among men (4–8 drinks/day).

The purpose of this large, observational study was to examine the influence of alcohol consumption in a non-clinical population on tasks demonstrating clear cognitive sex-differences. Participants were tested on additional cognitive tasks that were part of the larger study from which our sample was derived, enabling conclusions to be drawn with respect to the task specificity of potential effects. Furthermore, we used biological measures, such as blood gamma-glutamyl transferase (GGT) and mean corpuscular volume of red cells (MCV) to add an important biological dimension to our results for verifying and quantifying self-reports of drinking behaviour.


    SUBJECTS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Participants
The participants included 3000 women and men who had previously participated in the second data wave of the population-based, longitudinal Betula prospective study on memory, health and aging (for detailed description of purposes and study design, see Nilsson et al., 1997Go). The original Betula subject population consisted of 1500 women and 1500 men randomly sampled from Umeå, Sweden, who gave voluntary, informed consent for participation. Persons diagnosed with severe visual or auditory handicap, mental retardation, dementia, and persons having a native tongue other than Swedish were excluded from the sample. The ages ranged from 35 to 85 years. Participants were sampled in 5-year age blocks with ~150 women and 150 men in each age cohort. All participants completed a medical examination and blood sampling and an interview of health status. Participants completed questionnaires on social and economic issues, critical life events, and had an extensive examination of memory functions. The health examination and blood sampling were conducted ~1 week before the cognitive testing at convenient appointment times throughout the day.

Participants were asked if they currently drink alcohol, never drink alcohol or were past drinkers. Those individuals who reported being past drinkers were excluded from the analysis owing to our focus on comparisons among true teetotallers and current drinkers of alcohol. This resulted in 2224 participants for further analysis. Participants reported the amount of alcohol they typically drank in a 1-month period. The amount of alcohol drunk was categorized by beer, wine and alcohol. These values were converted into normative, single drink values (beer = 12 oz, wine = 5 oz, liquor = 1.5 oz). We calculated the number of drinks consumed per week. Participants were classified into four sex-adjusted drinking groups: non-drinking (0 drinks/week), light drinking (female ≤1/week, male ≤6/week), moderate drinking (female = 2–7/ week, male = 7–14/week) and heavy drinking (female ≥8/week, male ≥15/week) (National Institute on Alcohol Abuse and Alcoholism, 2000Go; Mukamal et al., 2003Go).

Materials and procedure
The cognitive tasks used were designed to evaluate multiple performance domains and included tasks of spatial visualization, episodic memory, and semantic memory. Trained research assistants conducted the cognitive testing, lasting between 1.5 and 2 h for each participant. A detailed description of tasks and test procedures can be found in Nilsson et al. (1997)Go. For the purpose of variable reduction and based on results of an earlier factor analysis of the Betula study task battery (Nilsson et al., 1997Go), composites were made for each main measure: spatial visualization, episodic memory, and semantic memory.

Mini-mental state examination (MMSE)
MMSE (Folstein et al., 1975Go) is a widely used test for determining global cognitive status and for screening of dementia. It assesses orientation, registration, attention, calculation, language and recall. Scores can range from 0 to 30; scores <24 are indicative of a cognitive dysfunction.

Spatial visualization
Spatial visualization is the ability to manipulate complex spatial information when several stages are needed to produce the correct solution (Linn and Petersen, 1985Go). Participants were asked to complete the block design task from the Wechsler Adult Intelligence Scale-Revised (Wechsler, 1981Go). A sub-task of the MMSE, draw-a-figure, was used as an additional assessment of spatial visualization. A composite spatial visualization score was computed by transforming the MMSE draw-a-figure score and block design score into separate z-scores, adding them and dividing by 2.

Episodic memory
Episodic memory is defined as the autobiographical record of unique life events in an individual's experience, encoded in a particular temporal–spatial context (Tulving, 1983Go). The global episodic memory score was derived from 13 episodic memory measures taken from nine episodic memory tasks. The episodic memory tasks were: word recall under four conditions of focused and divided attention (Baddeley et al., 1984Go), recall of newly acquired facts (Schacter et al., 1984Go), free recall, cued recall and recognition of sentences and subject-performed tasks (Cohen, 1981Go), face recognition (Olofsson and Bäckman, 1996Go), and recall of performed activities (Kausler and Hakami, 1983Go). The global episodic memory score was calculated by adding z-scores of the 13 episodic memory measures and dividing by 13.

Semantic memory
Semantic memory refers to our knowledge of the world (Tulving, 1983Go). Two tasks, recall of general knowledge (Schacter et al., 1984Go) and word comprehension (Nilsson et al., 1997Go) were used in order to assess semantic memory. Sex differences were not apparent in semantic memory (Herlitz et al., 1997Go). A composite semantic memory score was derived from the summed z-scores of these tasks, divided by 2.

Statistical methods
Apart from simple descriptive statistics and Pearson correlations, we used multiple analysis of covariance (MANCOVA) with a control of the two variables known to contribute to cognitive task performance, age and education. We assessed the main effects of drinking group and sex on the cognitive composites and the statistical interaction between group and sex. Analyses were conducted with SPSS statistical software package.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Participant characteristics
Table 1 shows the demographic characteristics for each drinking group separately for men and women. For both men and women, the mean level of alcohol consumption decreased as age increased. Education level, for both sexes, was higher among groups that drank more heavily. There was a significantly higher percentage of low MMSE scores among the non-drinking group when compared with the moderate drinking group in women. More women in the higher drinking groups were married than the non-drinking group and there were fewer married men in the non- and heavy drinking groups.


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Table 1. Participant characteristics by sex and drinking group (mean ± SD, or percentage)

 
Sleeplessness was less of a problem for women in groups with higher levels of alcohol consumption; however, among men, those in the non- and heavy drinking groups reported more problems with sleeplessness. Fewer men in the non-drinking group felt healthy and more of these men used prescription medication when compared with men in the other drinking groups. Smoking, for both sexes, was higher among groups that drank more alcohol.

Group differences in cognitive composites
The relationships between drinking groups, sex and cognitive performance were examined using a MANCOVA with statistical control of age and education. The dependent variables were the cognitive task composites (spatial visualization, episodic memory, semantic memory) and the independent variables were the drinking group (non, light, moderate, heavy) and sex (male, female). The overall MANCOVA showed both a significant effect of drinking group on cognitive performance, Wilks {lambda} = 0.99 (F = 2.57, 12/5667 d.f., P ≤ 0.022), as well as a significant effect of sex, Wilks {lambda} = 0.96 (F = 21.62, 4/2142 d.f., P ≤ 0.001), but no interaction.

In order to specifically evaluate the effects of drinking group on each cognitive composite, the information from the univariate F tests in the MANCOVA was used (see Table 2). The ANCOVA results showed significant drinking group differences for the episodic and semantic composites. Only the episodic and spatial visualization composites showed significant associations with sex. There were no sex by drinking group interactions. The age and education-adjusted mean of the spatial visualization composite for men and women show that the spatial visualization performance of men in the heavy drinking group approached the same value as women in the heavy drinking group, with the overall sex differences in the expected direction. Furthermore, women had higher age and education-adjusted mean scores on the episodic memory composite, as expected.


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Table 2. Cognitive task results for each drinking group by sex with control of age and education, mean (SE)

 
Pairwise comparisons using Bonferroni multiple comparison adjustments of drinking group means, with control of age and education, found significant sex differences for spatial visualization for the non- and light drinking groups (non-drinking, P ≤ 0.02; light drinking, P ≤ 0.001). This sex difference disappeared in the moderate and heavy drinking groups (moderate drinking, P ≤ 0.07; heavy drinking, P ≤ 0.63). Similarly, pairwise comparisons with Bonferroni adjustments for all drinking group means found significant sex differences for the episodic memory composite for nearly all drinking groups (non-drinking, P ≤ 0.06; light drinking, P ≤ 0.001; moderate drinking, P ≤ 0.001; heavy drinking, P ≤ 0.002). In the semantic memory composite, the only significant sex differences were found in the moderate drinking group (P ≤ 0.03).

Smoking has also been implicated as having an impact on cognitive function (Hill et al., 2003Go). Since we observed significant increases in smoking with increasing alcohol consumption, we re-ran the MANCOVA using the number of cigarettes smoked as a covariate with age and education. We found the same significant pattern of results with a significant effect of drinking group, Wilks {lambda} = 0.98 (F = 1.86, 9/2490 d.f., P ≤ 0.05) as well as a significant effect of sex, Wilks {lambda} = 0.97 (F = 9.16, 3/1023 d.f., P ≤ 0.001), but no interaction. Post-hoc ANCOVAs found significance for drinking group on episodic memory (F = 4.09, 3/1025 d.f., P ≤ 0.007), but the value for semantic memory approached significance with no drinking group significance on spatial visualization. The expected sex differences were evident in episodic memory (F = 18.25, 1/1025 d.f., P ≤ 0.001), but the value for spatial visualization approached significance. Semantic memory did not demonstrate sex differences, nor were there any interactions between drinking group and sex. Thus, smoking did not have a substantial impact on cognitive function in our study.

Drinking and blood markers of alcohol consumption
To verify the self-reported drinking levels, correlations between known biomarkers of excessive alcohol consumption, GGT and MCV, were run with the number of drinks/day. Because of innate biological differences between men and women and the different levels of alcohol consumed, we conducted the correlations separately for men and women. In women, we found a modest, positive relationship between these markers and the number of drinks/day (GGT, r = 0.09, P ≤ 0.001; MCV, r = 0.12, P ≤ 0.001). Similarly in men, we found a significant positive relationship with drinks/day (GGT, r = 0.23, P ≤ 0.001; MCV, r = 0.24, P ≤ 0.001).

Drinking groups only
The non-drinking group in our sample was significantly older and less educated than participants in the drinking groups. They also tended to report feeling less healthy and using more prescription medications compared with participants in the other groups. Furthermore, there was a higher percentage in this group with MMSE scores ≤24. Although the initial analysis included statistical controls for age and education, we also conducted a set of analyses in which the non-drinking group was eliminated. Re-analysis showed the same pattern of results with both a significant effect of the three drinking groups on cognitive performance, Wilks {lambda} = 0.99 (F = 2.36, 6/4034 d.f., P ≤ 0.028), as well as a significant effect of sex, Wilks {lambda} = 0.97 (F = 23.7, 3/2017 d.f., P ≤ 0.001), but no interaction. The post-hoc ANCOVAs showed a significant effect of drinking group on both episodic memory (F = 3.70, 2/2019 d.f., P ≤ 0.03) and semantic memory (F = 5.89, 2/2019 d.f., P ≤ 0.003), as well as sex on both episodic memory (F = 51.84, 1/2019 d.f., P ≤ 0.001) and spatial visualization (F = 4.14, 1/2019 d.f., P ≤ 0.04). These age and education-adjusted means for each cognitive composite, shown by sex and drinking group, are illustrated in Fig. 1.



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Fig. 1. Figures for drinking only groups demonstrating sex differences on composites of episodic memory, spatial visualization, but not on semantic memory (age and education-adjusted means).

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The goal of our investigation was to examine the influence of alcohol consumption in a non-alcohol dependent population on tasks demonstrating clear cognitive sex differences. We found sex differences in spatial visualization that were apparent in the non- and light drinking groups; however, the higher performance of men on spatial visualization tasks declined in the moderate and heavy drinking groups compared with women drinkers in the same sex-normative drinking groups. Conversely, the better performance of women on episodic memory tasks was apparent across all levels of alcohol consumption compared with men. Thus, increased levels of alcohol consumption appear to mitigate sex differences in spatial visualization, but seem to have little influence on sex differences in episodic memory performance. Our results are in general agreement with sex differences found in two previous epidemiological studies (Dufouil et al., 1997Go; Elias et al., 1999Go), and importantly, we extend their findings with respect to sex-specific memory and visuospatial processes as well as linking biomarkers to alcohol consumption.

The tasks chosen for this analysis were part of the larger Betula study on memory, health and aging. Previous work with the data from the Betula study has demonstrated through a factor analysis (Nilsson et al., 1996; Herlitz et al., 1997Go) that the tasks used are reliable and show consistent sex differences (episodic memory and spatial visualization) or are sex neutral (semantic memory) (Yonker et al., 2003Go). When comparing cognitive performance between men and women based on alcohol consumption, it is important to examine tasks in which clear-cut sex differences have been established in order to understand how alcohol may influence those spheres of cognition that show a sex-sensitive function.

Biological processes may be at work in the observed sex differences of spatial visualization and episodic memory. Alcohol abuse, even without evidence of detectable alcoholic liver disease, can cause severe gonadal failure in both men and women (Van Thiel, 1990Go). A growing body of evidence has indicated that alcohol may promote the aromatization of androgens to oestrogens in males (Purohit, 2000Go). Additionally, a literature review has concluded that alcohol can induce a rise in oestrogen levels in women (Gill, 2000Go). We speculate that our results indicate the influence of alcohol-induced elevation of oestradiol levels impacting cognitive task performance. Previous research has found that higher levels of testosterone that aromatized to increased oestradiol levels in men may interfere with the spatial task performance (Janowsky et al., 1994Go; Yonker et al., 2003Go). Our results indicate that the spatial visualization superiority demonstrated by men in the non- and light drinking groups disappeared in the moderate and heavy drinking groups. We can speculate, therefore, that higher alcohol consumption could have raised oestradiol levels that, in turn, influenced the block design performance. On the other hand, oestradiol has often been associated with a higher episodic memory ability in women (Yonker et al., 2003Go). The mean episodic memory scores of the women showed a steady increase with increased alcohol consumption, leading to the assumption that alcohol-induced oestradiol levels could have benefited the episodic memory performance in women. Actual oestradiol values will help shed light on these speculations.

Studies in chronic alcoholics have found a substantial atrophy of various brain regions, most notably, the prefrontal and cerebellar cortex (Spencer and Hutchinson, 1999Go). The prefrontal cortex is the brain region principally involved in higher cognitive processes, particularly visuospatial tasks (Carlson et al., 1998Go). Although we did not have diagnoses of alcoholism in our heavy drinking male participants, it is possible that the levels of alcohol they reported consuming, particularly if that level was maintained over several years, could produce a brain atrophy of the prefrontal cortex. This atrophy of the prefrontal cortex may be the explanation for the relative spatial visualization deficits observed in our heavy drinking male participants. Longitudinal drinking and spatial visualization data will eventually provide results that could offer more support to this hypothesis of prefrontal brain atrophy over time.

Parsons and Nixon (1998)Go have put forth the alcohol-causal-threshold hypothesis to help explain the existing literature and propose directions for future research. On studying our data in which sex-specific tasks were used, we could propose that in men, the significant sex advantage in spatial visualization performance disappears with an average of 3 drinks/day. Therefore, for men in our study, the proposed threshold for spatial visualization deficits is 3 drinks/day. This result lends support to the conclusions drawn by Parsons (1998)Go that at least 21 drinks/week can facilitate the appearance of neurocognitive inefficiencies or deficits in social drinkers. We are not able to apply the alcohol-causal-threshold hypothesis to the women in our study, since the episodic memory advantage displayed by women was consistent for all drinking groups. It is possible that our data for women could lend support to the J-shaped curve hypothesis for social drinkers, such that low to moderate drinkers performed at a better cognitive level than did non-drinkers or heavy and/or alcohol-dependent drinkers (Hendrie et al., 1996Go). We cannot unequivocally support the J-shaped hypothesis strictly with our data because we did not have reported levels of alcohol consumption in the abuse or dependence range for women, or diagnoses of alcohol dependence. Based on our results, we propose that any hypothesis explaining cognitive function and alcohol consumption should take gender into account, as well as the type of cognitive deficit.

A possible limitation of our study is the validity of self-reported measures of alcohol consumption. Although most studies on drinking and cognition use self-report drinking measures, a legitimate concern arises about the bias resulting from an inaccurate recall or intentional misreporting. In the Betula study, participants were asked how much they typically drank in 1 month; therefore, no long-term recall was required. Furthermore, the question on alcohol consumption was a very small part of the overall questionnaire, the main focus of which was general health and lifestyle issues, so there was no obvious threat to participants that could have led to less-than-candid responses. The significant correlations of GGT and MVC with drinks/day gave the expected positive results. Therefore, we are confident that the self-reported alcohol consumption values utilized in our study are unbiased.

The non-drinkers in our study were older, had lower education, had more prescription medication use and felt less healthy than drinkers. Abstinence from alcohol tends to increase among older individuals (Adams et al., 1990Go). Additionally, less healthier lifestyles tend to amass in individuals with lower education levels, and systemic diseases have been associated with a lower cognitive function (Waldstein and Elias, 2003Go). It is possible, therefore, that the socio-economic and quality of life factors, such as poor nutrition and increased disease, could have contributed residual effects related to a poorer cognitive performance, even though age and education variables were statistically controlled in our analyses. Irrespective of differences among the non-drinking group, reanalysis of the data with only three drinking groups illustrated the same overall pattern of effects.

In summary, sex differences in cognitive function appear to be impacted by alcohol consumption for spatial visualization, but not episodic memory. Our results lend support to the alcohol-causal-threshold hypothesis (Parsons, 1998Go), specifically spatial visualization in men. The results observed with episodic memory in women tend to support the J-shaped curve hypothesis (Hendrie et al., 1996Go). It is important to note that, even with as few as 3 drinks/day, men begin to show a cognitive impairment in visuospatial ability. The clinical, social and lifestyle relevance of this impaired cognitive ability in men is not yet known; nonetheless, the negative impact could be substantial. Furthermore, our results lend support that among women, alcohol consumption may have a beneficial effect on cognitive ability, specifically episodic memory. Our study highlights that sex differences are important factors to consider in relation to alcohol consumption. Not only do men and women differ in their drinking behaviour and alcohol metabolism, but their susceptibility to cognitive deficits in tasks in which they typically excel is also differentially influenced by alcohol consumption.


    ACKNOWLEDGEMENTS
 
This study was funded in part by NIH grant # AA013307. In addition, the Betula study was supported by the Bank of Sweden Tercentenary Foundation, the Swedish Council for Planning and Coordination of Research, the Swedish Council for Research in the Humanities and Social Sciences, and the Swedish Council for Social Research. We thank all members of the Betula project for collaboration and data collection.


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 RESULTS
 DISCUSSION
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