Abstract
The present study aimed to establish whether habitual alcohol consumption benefits verbal and spatial working memory performance after addressing the main criticisms that have been raised against the finding that alcohol benefits cognition. An adult lifespan sample of 1,652 healthy adults between 21 and 80 years of age participated in the study. Participants were classified as lifetime nondrinkers or drinkers, and several demographic and biological variables were controlled. Alcohol consumption was assessed through a lifestyle questionnaire created for the study. Working memory was measured through a 2-back computerized task. Discrimination and speed in verbal and spatial working memory among drinkers were superior to those among nondrinkers. Total alcohol intake across life and the amount of alcohol intake per week predicted higher verbal and spatial working memory discrimination. Beer drinkers showed more accurate and faster responses in verbal and spatial working memory than nondrinkers, wine drinkers and spirit drinkers. The optimal amount of alcohol intake to benefit working memory for women and men was 100 g per week, which is equivalent to one drink per day. After consuming 350 g of alcohol per week, equivalent to 25 drinks per week, the effects of alcohol on working memory become more negative than the effects of alcohol abstinence. While alcohol consumption is considered a risk factor for several diseases, we found that moderate alcohol intake benefits working memory performance throughout the adult lifespan to a greater extent than whole-life abstinence.
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Introduction
Alcohol abuse undoubtedly has harmful effects on several health areas (Wood et al., 2018), and the only safe amount of alcohol consumption to avoid health damage has been suggested to be zero (GBD 2016 Alcohol Collaborators, 2018). Although alcohol consumption might be a precursor of several health problems, numerous studies have provided evidence that moderate alcohol consumption benefits cognitive function and protects against all types of dementia, including Alzheimer’s disease. These findings have been replicated by several reviews and meta-analyses, two of which are remarkable due to the number of studies covered—49 (Panza et al., 2009) and 143 (Neafsey & Collins, 2011) studies. A sco** review that analyzed 28 systematic reviews reached the same conclusion (Rehm et al., 2019).
Alcohol research controversies
Evidence from the literature indicates that moderate alcohol consumption might benefit brain function (e.g., Stancampiano et al., 2004). However, researchers in this field have reached various conclusions regarding the effect of alcohol consumption. The strongest arguments against the studies concluding that moderate alcohol consumption benefits cognitive function are related to methodological procedures. For example, cognitive differences between drinkers and nondrinkers have been attributed to participants’ misclassification because several studies included individuals who quit drinking together with pure abstainers in the group of nondrinkers (Shaper et al., 1988). However, individuals who quit drinking might have adopted this choice because they are affected by an illness; consequently, the nondrinker group might be at a disadvantage compared with the drinker group. Thus, any difference between groups could not be controlled by this underlying confounder. The potential effect of this confounding is even stronger when the studies include older adults. Another argument against the studies concluding that alcohol benefits cognition is the lack of sufficient control variables.
These limitations—the inadequate selection of nondrinker participants or the insufficient inclusion of control variables—contribute to the strong controversy regarding whether the effects of alcohol are linear or U-shaped. Linear effects indicate that higher alcohol intake corresponds to greater harmful effects. The linear effects of alcohol on memory functioning were first proposed based on the continuous memory deficits observed during social drinking, drinking-induced amnesia or blackouts, until severe alcoholic syndromes (Ryback, 1971). U-shaped effects were supported by the association between moderate alcohol intake and higher cognitive performance observed among moderate drinkers compared to nondrinkers or heavy drinkers (for a review, see Kim et al., 2012).
The linear effects of alcohol on memory are undeniable in individuals ranging from social drinkers to alcoholic drinkers, such as those with Wernicke-Korsakoff syndrome. However, U-shaped effects of alcohol on cognition are controversial. Nevertheless, there is compelling evidence suggesting that moderate alcohol consumption is associated with higher cognitive performance than abstaining or drinking heavily. A prospective cohort study (Zhang et al., 2020) that included a representative sample of 19,887 adults in the United States with a mean age of 62 years found U-shaped effects on total cognition scores. Participants from this study were followed for nine years, and the optimal drinking dose to maintain a low risk of cognitive decline was 12 drinks per week.
Effects of alcohol on cognition
The benefit of moderate alcohol consumption for cognition can be further debated because this conclusion is founded on global measures of cognition. Most studies used a single assessment test, such as the Mini-Mental State Examination (MMSE), or a battery of neuropsychological tests to obtain a global cognitive measurement (Neafsey & Collins, 2011; Panza et al., 2009). However, the benefits for cognition might be overestimated because some cognitive abilities are unaffected by advancing age, while others, such as memory processes, are severely impaired (Glisky, 2007). Thus, a global cognitive measurement obscures the exact effect of alcohol on specific cognitive processes.
For example, a study that followed 1,488 individuals for 11.5 years (Leroi et al., 2002) reported that cognition declined less in habitual drinkers than in nondrinkers, in terms of MMSE scores. Likewise, a cross-sectional study (Wright et al., 2006) conducted on 2,215 participants with a mean age of 68 years reported that compared to abstainers, women who drank between 1 drink/week and 2 drinks/day had higher MMSE scores. Global cognitive measures have been obtained even by telephone interviews (Stampfer et al., 2005). This method was employed to assess 10,102 women between 70 and 81 years old who were followed for two years. Moderate alcohol consumption, defined as consuming up to 15 g per day (equivalent to one drink) in this study, was associated with better cognitive scores than nondrinkers.
Furthermore, the benefit of moderate alcohol consumption on cognition has been observed mainly in older adults (e.g., Peters et al., 2008) because most studies have focused on this life stage. Indeed, studies examining young and middle-aged adults found no cognitive differences between drinkers and nondrinkers (Neafsey & Collins, 2011). However, these findings are based on studies focusing on these specific life stages and have not been directly compared with findings for older adults in the same study and under the same circumstances.
Effects of alcohol on working memory
The purpose of the present study was to provide reliable evidence of the potential benefits of moderate alcohol intake by considering the shortcomings of previous studies. We focused on working memory because independently examining each cognitive domain, particularly those that drastically change during the course of adulthood, is necessary to advance our knowledge of cognitive function. Working memory is one of the cognitive domains most affected by the aging process (Cansino et al., 2013; Park et al., 2002). Global measures of cognition are useful screening tests to estimate the general cognitive function of an individual but do not provide any information about the function of specific cognitive domains.
Working memory is active during most of our waking time and is crucial to accomplish all everyday mental operations, such as understanding a conversation, following instructions, or solving problems. Working memory refers to our ability to retain information for a short period—a few seconds—and to transform that information according to the purpose of the task at hand (Baddeley & Hitch, 1974). Several other models of working memory have expanded our understanding of this process, such as the embedded-process model (Cowan, 1999), which emphasizes the limited capacity, interaction with long-term memory, and need for attention to process information of working memory.
Moreover, working memory is used to execute our plans (Miller et al., 1960), and for that reason, it is crucial for cognitive function. Therefore, working memory should not be viewed as an isolated system because its control processes support the accomplishment of goals of other systems, such as sensory systems, motor systems, and long-term memory systems (D’Esposito & Postle, 2015). Due to the relevance of working memory to overall cognition, it is important to examine how habitual consumption of alcohol may influence its function. The effect of regular moderate alcohol consumption exclusively on working memory has not been previously examined in observational studies because, as mentioned, most studies have focused on global cognitive measures.
However, several studies have investigated the effects of acute alcohol administration on working memory. According to a meta-analysis that included 32 studies (Spinola et al., 2022), experimentally controlled administration of alcohol produced small to mild working memory deficits in young adults. We examined working memory with an n-back task (Kirchner, 1958) in the verbal and spatial domains. We used a 2-back level of difficulty because such a task requires the use of the main processes that define working memory, such as storage, binding, retrieval, updating, monitoring and interference control. The tasks were computerized, which allowed us to precisely measure the accuracy and speed of accessing information from working memory. The effect of alcohol intake on working memory speed has not been examined previously in an observational study.
Current study
In summary, the effects of habitual alcohol consumption on cognition have been extensively investigated in older adults but less frequently explored in young and middle-aged adults. Longitudinal and cross-sectional observational studies have consistently found that moderate alcohol consumption benefits cognitive performance compared to alcohol abstinence or heavy alcohol intake. However, these findings have been questioned due to issues with methodological procedures, such as misclassification of complete abstainers and lack of sufficient control variables. Additionally, most studies have examined the effects of alcohol consumption on global cognitive measures that may be imprecise because they are based on several cognitive domains; not all of these domains may be influenced by alcohol as aging only affects specific cognitive domains.
Therefore, we exclusively examined the effects of alcohol consumption on working memory due to its crucial role in several cognitive processes. Moreover, we employed a computerized task that allowed us to assess discrimination and speed in verbal and spatial working memory. These measurements have not been collected before because observational studies have mostly used paper-and-pencil assessments that are less accurate and provide less experimental control. Additionally, we examined a lifespan sample of 1,652 healthy adults between 21 and 80 years old. To the best of our knowledge, this study is the first to examine the effects of habitual alcohol consumption on working memory in an adult lifespan sample. If alcohol has a positive effect on memory, these effects should be observed at any age; thus, a lifespan sample allows us to confirm this prediction. Moreover, we carefully included only complete abstainers (for their entire lives) in the nondrinking group to ensure that such participants were not mixed with former drinkers. Furthermore, we examined individuals of all ages to rule out the possibility that nondrinkers might be affected by any illness that could explain memory performance differences between drinkers and nondrinkers. To assess the effect of alcohol intake on working memory, we first controlled for several demographic and biological variables to overcome one of the main criticisms of previous studies. Among these variables, we included scores on the Beck Depression Inventory (BDI) (Beck, 1987), vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (Wechsler, 1981), and MMSE (Folstein et al., 1975). Therefore, the exact amount of variation in working memory explained by alcohol consumption was estimated after controlling for several variables, including depression traits, intellectual difficulties and global cognition.
The aims of the current study were as follows. (i) We aimed to compare discrimination and speed in verbal and spatial working memory between habitual alcohol drinkers and nondrinkers. (ii) We aimed to estimate the effects of total alcohol intake and quantity of alcohol intake per week (including quantity of specific alcoholic drinks—beer, wine, liqueur and spirit—consumed) on discrimination and speed in verbal and spatial working memory. The exact influence of alcohol on working memory was estimated after controlling for several demographic and biological variables. (iii) We aimed to examine differences in discrimination and speed in verbal and spatial working memory between groups that consumed different alcoholic drinks and nondrinkers. (iv) We aimed to examine whether drinking patterns changed across the adult lifespan. The quantity of alcohol intake per week and the quantity of each type of alcoholic drink consumed per week was compared across the six decades between 21 and 80 years old. (v) We aimed to evaluate whether individuals exhibited an alcohol consumption trend over decades. (vi) We aimed to construct dose‒response curves for verbal and spatial working memory as a function of the quantity of alcohol intake per week, controlling for demographic and biological variables.
The main question motivating this study was whether habitual alcohol consumption influences discrimination and speed in verbal and spatial working memory throughout the adult lifespan. We tested several hypotheses (listed below). The first two hypotheses were based on the fact that numerous studies (Neafsey & Collins, 2011) have shown that moderate alcohol consumption has positive effects on cognition; therefore, we expected that this benefit would also be observed for working memory. Part of the second and third hypotheses are based on the protective effects of wine consumption against cognitive decline, as demonstrated in a meta-analysis that included 12 longitudinal studies (Lucerón-Lucas-Torres et al., 2022). The fourth and fifth hypotheses were based on alcohol consumption changes reported in a study that included 6,011 individuals (Britton & Bell, 2015). The sixth hypothesis was based on the finding that moderate alcohol drinkers showed higher cognitive performance than nondrinkers and heavy drinkers (Kim et al., 2012).
Hypothesis 1
Discrimination and speed in verbal and spatial working memory will be higher in drinkers than in nondrinkers across the entire lifespan sample.
Hypothesis 2
Total alcohol intake and quantity of alcohol intake will significantly predict higher discrimination and speed in verbal and spatial working memory after controlling for possible cofounders. Among different alcoholic drinks, wine will provide stronger benefits for working memory than beer, liqueur, or spirits.
Hypothesis 3
Discrimination and speed in verbal and spatial working memory will be higher for wine drinkers than for beer, liqueur and spirit drinkers as well as nondrinkers.
Hypothesis 4
The quantity of alcohol intake per week and quantity of each type of alcoholic drink consumed per week will change across the decades between 21 and 80 years old.
Hypothesis 5
A trend toward less consumption of alcohol per week will be observed across decades.
Hypothesis 6
The dose‒response curves will exhibit a U-shape, indicating that moderate alcohol intake has greater positive effects on verbal and spatial working memory than alcohol abstinence and heavy drinking.
Materials and methods
Participants
A sample of 1,652 healthy adults (831 women, 821 men) between 21 and 80 years old participated in the study. Table 1 displays the participants’ characteristics and scores on neuropsychological tests among drinkers and nondrinkers. The sample population was recruited through word of mouth, advertisements, flyers and appeals to community groups. The inclusion criteria were completion of at least eight years of education, normal or corrected-to-normal vision, a score ≤ 20 on the BDI (Beck, 1987), a score ≥ 24 on the MMSE (Folstein et al., 1975), and a score ≥ 26 on the vocabulary subtest of the WAIS-R (Wechsler, 1981). These performance scores guaranteed that the participants were not suffering from depression, dementia, or intellectual difficulties. The exclusion criteria were addiction to drugs or alcohol, consumption of medication that acted on the nervous system in the previous six months, a diagnosis of neurological or psychiatric diseases, and head trauma. The study was approved by the Bioethics Committee of the School of Medicine at the National Autonomous University of Mexico.
The experiments were performed in accordance with the Declaration of Helsinki. All participants provided informed consent and received a monetary reward for their participation.
Measures
A questionnaire was created for the current study to examine alcohol consumption and other lifestyle variables. Participants indicated the number of glasses of alcohol that they usually had when they drank and reported the alcoholic beverage that they drank the most frequently (beer, wine, liqueur or spirits). Alcohol consumption frequency was classified into 10 categories (never, once a year, three times per year, six times per year, once per month, two or three times per month, one or two times per week, three or four times per week, almost every day and daily). Likewise, participants reported how long they had been drinking and from what age. Total alcohol intake was calculated as the frequency per duration. According to the National Institute on Alcohol Abuse and Alcoholism (2022), a standard drink contains 14 g of pure alcohol regardless of the alcoholic beverage. This conclusion is based on the fact that the amount of alcohol in one alcoholic drink is approximately equivalent even if drinks are served in different container sizes and the percentage of alcohol by volume varies among them. Therefore, the amount of alcohol intake per week was estimated as the product of the number of drinks per 14 g.
N-back stimuli
Twelve uppercase letters (B, F, G, K, L, N, P, Q, R, S, T and X) were used in the verbal version of the n-back task. Each letter had vertical and horizontal visual angles of 1.5° and 1°, respectively. The letters were presented in a dark gray color at the center of a white screen to maintain low contrast. A dark gray circle with a visual angle diameter of 1.5° was used in the spatial version of the n-back task. The screen was white in color, and a black cross (vertical and horizontal visual angles of 0.5°) was continuously displayed at the center of the screen. The circle was displayed in one of 12 possible positions around the center of the screen. The distance between the circle and the center of the screen was 4°. The letters for the verbal task and the positions for the spatial task were selected randomly and with the same probability.
Procedures
The participants attended two sessions lasting approximately two hours each. Prior to being invited to attend the first session, a set of prescreening questions was used to determine whether potential participants fulfilled the inclusion and exclusion criteria. The first session occurred in a silent room in which only one participant and the experimenter were present. During the first session, the participants were further interviewed to determine whether they satisfied the inclusion and exclusion criteria. Next, the participants completed the WAIS-R Vocabulary subtest, the MMSE and the BDI, and their vision was tested. Participants who were eligible for the study were asked to provide their informed consent. Then, the participants were interviewed about their lifestyle and alcohol consumption. The purpose of the interview was to collect information on education level, employment status, income, health status, medication intake, alcohol consumption, and cultural, social, mental and physical activities. The questions were formulated as a semistructured interview. Finally, the participants’ weight and height were measured. The second session took place one week after the first session. In the second session, participants’ glucose, cholesterol and triglycerides were measured in a nonfasting state with the Accutrend Plus System (Roche Diagnostics, Rotkreuz, Switzerland). These measurements were taken in a counterbalanced order. Then, blood pressure and heart rate were measured with a digital upper arm sphygmomanometer (Hem-712 C, Omron, Kyoto, Japan). Subsequently, the participants performed a working memory task and a source memory task (data not shown) in a sound-dampened chamber. The participants performed the verbal and spatial n-back tasks in counterbalanced order, and within each domain, they were subjected to two levels of difficulty (1-back and 2-back) in counterbalanced order. Data from the 1-back task were not included in the analyses because this task demands few processing resources, and some participants’ performance showed ceiling effects. Prior to performing each of the four n-back tasks, the participants performed brief versions of each task as training. The participants performed the task seated in a high-back armchair located 100 cm away from the monitor screen. A response panel was located on a platform placed on either the left or right arm of the chair at a comfortable distance according to the participants’ handedness. Stimulus presentation and response recording were controlled by E-Prime software, version 1.0 (Psychological Software Tools, Pittsburgh, PA, USA).
Working memory paradigm
For both the verbal and spatial n-back tasks, each trial started with presentation of the stimulus (letter or circle) for 300 ms, followed by a period of 2700 ms. After this time, the next stimulus was displayed. During the 3000-ms period following stimulus onset, the participants were allowed to provide their response. In the verbal 2-back task, the participants indicated whether the current letter was equal or not equal to the letter displayed two trials prior. In the spatial version of the 2-back task, the participants indicated whether the current circle was presented in the same position as the circle displayed two trials before. The participants performed 72 trials from each version of the task, 33% of which were target trials (letters or positions equivalent to those of the current trial).
Data analysis
Working memory was estimated as the discrimination levels on the verbal and spatial.
2-back tasks using d-prime (d′) values because they are not affected by the participants’ criteria for performing the tasks. All variables were examined with descriptive analyses, and those with skewness exceeding ± 3 were natural log-transformed. Differences in discrimination and speed in the verbal and spatial working memory tasks and in participant characteristics between the nondrinker and drinker groups were analyzed using independent-sample t tests (two-tailed). For variables with unequal variance between groups, the degrees of freedom were corrected with Satterthwaite’s procedure. For dichotomous variables, we employed χ2 analyses. To correct for multiple comparisons, we used the Bonferroni procedure.
Hierarchical regression analyses were conducted to further determine the influence of alcohol consumption on verbal and spatial working memory discrimination levels and speed in both memory processes. Hierarchical regression analyses were estimated for total alcohol intake and for the quantity of alcohol intake per week (g/w). Additionally, these two variables were analyzed for specific alcoholic beverages (beer, wine, liqueur and spirits). For the first step, the following demographic variables were introduced: age, sex, years of education, vocabulary scores, MMSE scores and BDI scores. For the second step, the following biological variables were entered: body mass index (BMI), glucose, cholesterol, triglycerides, heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Finally, for the third step, we entered the alcohol variable: total intake, intake quantity, or the total intake and intake quantity of each type of alcoholic drink. This procedure allowed the determination of the exact influence of alcohol on working memory performance after controlling for possible confounders.
To estimate whether distinct types of alcoholic drinks differentially influence memory performance, one-way analysis of variance (ANOVA) was conducted. Significant results were further analyzed by Tukey’s honest significant difference (HSD) tests to determine significant differences in memory performance between groups that consumed different alcoholic drinks and nondrinkers. To examine whether drinking patterns change across the lifespan, a one-way analysis of variance (ANOVA) was conducted on the quantity of alcohol intake per week across the six decades between 21 and 80 years old. Additionally, this same variable was analyzed for each type of alcoholic drink. Significant differences between decades were further analyzed by Tukey’s HSD tests. Trend analyses based on Cuzick’s test (Cuzick, 1985) were conducted to examine whether an alcohol consumption trend over decades exists.
The dose‒response effects were analyzed using the Stata module developed by Bia and Mattei (2008). This procedure incorporates the generalized propensity score proposed by Hirano and Imbens (2004). The dose‒response functions for verbal and spatial working memory performance were estimated for the quantity of alcohol intake with the same control variables introduced in the hierarchical regression analyses and 1000 bootstrap repetitions. All analyses were conducted by using Stata v. 16 (Texas, USA).
Results
Descriptive analysis results for all variables are displayed in Supplemental Material Table S1. Four variables still had skewness larger than ± 3 (total wine and liqueur intake and the quantities of wine and liqueur intake) after being log-transformed. Table 1 displays the demographic and biological characteristics of nondrinkers and drinkers. Significant differences were observed in age, sex and MMSE scores. However, age no longer significantly differed between the groups after applying the appropriate p value cutoff (p < .004) according to the Bonferroni procedure.
Working memory differences between drinkers and nondrinkers
The participants’ performance in the verbal and spatial working memory tasks is depicted in Fig. 1. Hypothesis 1 was that discrimination and speed in verbal and spatial working memory will be higher in drinkers than in nondrinkers; this hypothesis was supported. Discrimination for verbal (t(1650) = -3.30, p < .001, d = -0.19) and spatial (t(1650) = -4.17, p < .001, d = -0.26) working memory significantly differed between the nondrinker and drinker groups. Likewise, the speed at which correct responses were provided in the verbal (t(1,650) = 2.44, p = .015, d = 0.15) and spatial (t(1,650) = 2.31, p = .021, d = 0.14) working memory tasks differed significantly between nondrinkers and drinkers.
The mean and individual working memory discrimination and speed in the nondrinker and drinker groups. Error bars represent the 95% confidence intervals for the mean
The influence of total alcohol intake and quantity of alcohol intake
We hypothesized that total alcohol intake and quantity of alcohol intake would predict higher discrimination and speed in verbal and spatial working memory after controlling for several demographic and biological variables. Additionally, we expected that total wine intake and quantity of wine intake would benefit working memory performance to a greater extent than other alcoholic drinks (Hypothesis 2). This hypothesis was partially supported. Total alcohol intake and quantity of alcohol intake significantly predicted discrimination in verbal and spatial working memory but not speed. Wine did not influence working memory; instead, the consumption of beer and spirits showed significant effects. The results of the hierarchical regression analyses for total alcohol intake predicting working memory performance in the final step are displayed in Table 2; the results for the quantity of alcohol intake predicting working memory are shown in Table 3. The hierarchical results for the total intake and intake quantities of beer, wine, liqueur and spirits predicting working memory discrimination are displayed in Supplementary Material Tables S2, S3, S4 and S5, respectively. These analyses revealed that the intake quantity of beer in the third step significantly predicted verbal working memory (β = 0.05, 95% CI = [0.01, 0.09], p = .029) (R2 = 0.283, p < .001) (∆R2 = 0.002, ∆F = 4.747, p = .029). Additionally, the total intake of spirits in the third step significantly predicted spatial working memory (β = 0.05, 95% CI = [0.00, 0.09], p = .034) (R2 = 0.310, p < .001) (∆R2 = 0.002, ∆F = 4.387, p = .036). Because total alcohol intake and the quantity of alcohol intake did not significantly predict speed in working memory, speed was not further analyzed for each type of alcoholic drink.
The differential influences of types of alcoholic drinks on working memory
Hypothesis 3
predicted that discrimination and speed in verbal and spatial working memory would be higher for wine drinkers than for beer, liqueur and spirit drinkers as well as nondrinkers. This hypothesis was not supported; working memory performance was higher in beer drinkers than in drinkers of other alcoholic drinks and nondrinkers. The working memory performance for nondrinkers and drinkers of beer, wine, liqueur, and spirits is displayed in Fig. 2. Discrimination in the verbal [F(4, 1647) = 18.29, p < .001, partial η2 = 0.04)] and spatial [F(4, 1647) = 19.90, p < .001, partial η2 = 0.05)] working memory tasks differed significantly among groups. Tukey HSD tests revealed that for both verbal and spatial working memory, beer drinkers’ discrimination levels were superior to those for nondrinkers and drinkers of wine, liqueur and spirits. Likewise, speed in correct verbal [F(4, 1647) = 5.53, p < .001, partial η2 = 0.01)] and spatial [F(4, 1647) = 5.57, p < .001, partial η2 = 0.01)] working memory responses differed significantly between groups. Post hoc Tukey HSD tests revealed that beer drinkers were faster than wine drinkers, spirit drinkers and nondrinkers in both verbal and spatial working memory.
The mean and individual working memory discrimination and speed for individuals who never drank and individuals who drank beer, wine, liqueur, or spirits more often. Error bars represent the 95% confidence intervals for the mean
Changes in alcohol consumption patterns across the lifespan
We predicted that the quantity of alcohol intake per week and quantity of each type of alcoholic drink consumed per week would change across decades of the adult lifespan (Hypothesis 4). Likewise, we hypothesized that across decades, there would be a trend toward consuming less alcohol per week (Hypothesis 5). Hypothesis 4 was supported regarding total alcohol intake per week but not each type of alcoholic drink. Hypothesis 5 was supported. The quantity of alcohol intake per week among decades was significant [F(5, 1328) = 2.53, p = .028, partial η2 = 0.01)]. Tukey HSD tests revealed that the amount of alcohol intake per week was higher in individuals aged 21–30 years (M ± SD: 2.99 g/w ± 1.48) than in those aged 41–50 years (2.65 g/w ± 1.61), 51–60 years (2.61 g/w ± 1.68), 61–70 years (2.68 g/w ± 1.58) and 71–80 years (2.51 g/w ± 1.50). The amount of alcohol intake among individuals between 31 and 40 years old (2.75 g/w ± 1.51) did not differ from that in the other decades. The quantity of beer [F(5, 407) = 1.80, p = .112, partial η2 = 0.02)], wine [F(5, 181) = 0.16, p = .976, partial η2 = 0.004)], liqueur [F(5, 39) = 0.81, p = .548, partial η2 = 0.09)] or spirit [F(5, 683) = 0.30, p = .913, partial η2 = 0.002)] intake did not vary significantly among decades. The trend analysis based on the Cuzick test was significant for the quantity of alcohol intake across decades (z = -3.31, p < .001).
Dose‒response curves
Hypothesis 6
predicted that dose‒response curves would show a U-shape, demonstrating that moderate alcohol intake benefits verbal and spatial working memory to a greater extent than alcohol abstinence or heavy drinking. This hypothesis was supported. Figure 3 depicts the dose‒response function and the treatment effect function or derivative for the quantity of alcohol intake per week as the treatment variable.
Dose‒response function for working memory discrimination and the treatment effect function (marginal or derivative) for the quantity of alcohol intake per week as the treatment variable. Additionally, the 95% confidence intervals are displayed after 1000 bootstrap replications
Discussion
The more relevant findings were that discrimination in both verbal and spatial working memory was higher in individuals who drink than in individuals who never drank. Furthermore, drinkers were faster in accessing information from verbal and spatial working memory than nondrinkers. After controlling for several demographic and biological variables, participants’ lifelong intake of alcohol and the amount of alcohol intake per week significantly predicted enhanced discrimination in verbal and spatial working memory. The quantity of beer intake and the total intake of spirits significantly predicted verbal and spatial working memory discrimination, respectively. Drinkers who preferably consumed beer showed higher verbal and spatial working memory discrimination than wine drinkers, liqueur drinkers, spirit drinkers and nondrinkers. Beer drinkers also showed faster responses in verbal and spatial working memory than wine drinkers, spirit drinkers and nondrinkers. The amount of alcohol intake showed a U-shaped dose‒response effect on both verbal and spatial working memory, indicating that 100 g/w of alcohol provides the best memory benefits. Next, we discuss these findings in detail.
Habitual alcohol consumption enhances working memory discrimination and speed compared with life-long abstinence; thus, alcohol has a broad effect on working memory performance. Moreover, the fact that both verbal working memory and spatial working memory benefit from alcohol intake indicates that the positive effects of alcohol encompass not only separated storage and rehearsal for verbal and spatial information but also central executive functioning, which is responsible for the control processes within the working memory system, such as assigning resources and allocating attention.A remarkable finding is that alcohol intake increases the velocity of accessing information from both verbal and spatial working memory. Alcohol effects on memory speed, measured by means of exact reaction times, have not been reported previously. Speed has been examined for perceptual processing, but the results have not been consistent. Alcohol consumption has been associated with faster perceptual processing when measured by paper-and-pencil instruments (Kumari et al., 2014; Zanjani et al., 2013) but with slower processing when measured by reaction times (Piumatti et al., 2018). The present results showed that at least for highly demanding cognitive processes, such as working memory, alcohol consumption increases speedy processing without affecting exactitude because this effect was observed in accurate responses.
The benefits of alcohol found here do not contradict findings in previous studies that observed harmful effects of alcohol consumption because these negative effects have been found to be potential precursors of specific diseases (Wood et al., 2018) or a risk factor for death or disability (GBD 2016 Alcohol Collaborators, 2018) but are not directly related to brain functioning or cognition. The present results do not contradict the finding that working memory is impaired when individuals are under the effects of alcohol in controlled experiments (Spinola et al., 2022) because in the present study, the benefits of alcohol on working memory were observed in individuals who habitually drink certain amounts of alcohol. Therefore, the mechanisms explaining the benefits of alcohol consumption differ from those explaining the harmful effects on severe diseases or during alcohol consumption.
Several mechanisms that might explain the benefits of alcohol have been observed. In studies with rats, low doses of ethanol have been found to increase the release of acetylcholine in the prefrontal cortex (Stancampiano et al., 2004). Another direct influence on brain function was observed in rats that were chronically given low doses of ethanol (Kalev-Zylinska & During, 2007). This study revealed that the rats showed improved memory, and this improvement was directly related to the increase in the expression of N-methyl-D-aspartate receptors (NMDARs) in the hippocampus, which are highly involved in the control of synaptic plasticity and memory. Alcohol effects on the increase in acetylcholine in the prefrontal cortex (Stancampiano et al., 2004) and on NMDAR expression in the hippocampus (Kalev-Zylinska & During, 2007) clearly explain the specific benefits observed for working memory in the current study because both brain regions are involved in working memory processes (Stern et al., 2001).
The contribution of the prefrontal cortex to working memory was discovered through extracellular recordings in monkeys (Fuster & Alexander, 1971; Kubota & Niki, 1971). These studies observed persistent neural activity during the retention period of working memory tasks. Subsequent research (for a review, see D’Esposito & Postle, 2015) revealed that the continuous activity observed in the prefrontal cortex was not merely related to the retention of information. This activity also reflects the maintenance of goals, strategies and rules that guide several brain systems to accomplish the task at hand. The prefrontal cortex is densely innervated by cholinergic projections; in particular, acetylcholine is known to contribute to working memory because its depletion in the prefrontal cortex severely impairs working memory (Wallace & Bertrand, 2013). Therefore, the increase in acetylcholine in the prefrontal cortex, as a consequence of moderate alcohol consumption (Stancampiano et al., 2004), may explain the observed benefits of alcohol consumption on working memory performance in the present study.
Hippocampal participation in working memory is supported by the finding that lesions of the medial temporal lobe in monkeys impair working memory (e.g., Gaffan, 1974). Hippocampal NMDAR expression is considered the main molecular mechanism that contributes to the initiation of synaptic plasticity and memory (Li & Tsien, 2009). The activation of postsynaptic NMDARs induces long-term potentiation, a synaptic modification that may contribute to long-term memory. Notably, NMDARs also contribute to working memory, which relies on sustained neuronal activity instead of synaptic modification. In particular, NMDARs produce recurrent excitatory and reverberant synapses that may be crucial for maintaining information within working memory (Lisman et al., 1998). The role of NMDARs in working memory was confirmed by the fact that their blockage severely impairs this function (e.g., Zhang et al., 2013). Moreover, alcohol increases the expression of NMDARs, which are a relevant receptor for ethanol within the brain (Kalev-Zylinska & During, 2007); this finding may also explain the benefit of moderate alcohol intake for working memory observed in the current study.
Studies in humans have also outlined several mechanisms explaining the benefit of moderate alcohol intake. However, these mechanisms are more general and not directly related to cognitive function. A meta-analysis (Rimm et al., 1999) including 42 studies that measured high-density lipoprotein (HDL) cholesterol before and after experimental alcohol administration for 1 to 9 weeks observed that alcohol increases the concentrations of HDL. Thus, a causal effect of alcohol intake on lipid configuration may prevent cerebrovascular complications. Another mechanism is the direct effect of moderate alcohol consumption on systemic inflammatory markers related to cerebrovascular disease. In a randomized study (Sierksma et al., 2002) in which a diet regimen was assigned to the participants—men consumed four glasses of beer and women consumed three glasses of beer at dinner for three weeks—the results revealed that plasma C-reactive protein and fibrinogen levels decreased compared to those in participants who were given nonalcohol beer. These findings have been replicated, and even more inflammatory markers that diminish as a result of moderate alcohol consumption have been detected. Imhof et al. (2004) observed in three representative samples from Germany, Scotland and France that moderate alcohol consumption was associated with lower blood levels of the inflammatory marker C-reactive protein, total white blood cell counts, fibrinogen, plasma viscosity and albumin.
Importantly, we also found that drinkers and nondrinkers differed in age, sex and MMSE scores. However, age was no longer significant according to the multiple comparison-corrected probability. The lower MMSE scores observed in the drinker group compared to the nondrinker group revealed that general cognition measures that cover several cognitive domains provide scores that may obscure performance on specific processes, such as memory. However, this result contradicts several previous studies that have consistently found that alcohol benefits general cognition (Neafsey & Collins, 2011; Panza et al., 2009). The difference in sex is due to more women belonging to the nondrinker group than to the drinker group, which may be attributed to cultural factors.
Total alcohol intake throughout life and the amount of alcohol consumed every week positively influenced verbal and spatial working memory discrimination after controlling for age, sex, MMSE scores, and several other biological and demographic variables. Moreover, the effects of alcohol within the hierarchical models significantly contributed to the explanation of working memory performance. The amount of beer intake enhanced verbal working memory, whereas the total intake of spirits increased spatial working memory after controlling for several variables, an effect that also contributed significantly to the models. Thus, the alcohol content of these beverages was more influential than the additional components with health benefits, such as antioxidant properties. Surprisingly, total spirit intake influenced spatial working memory, a task more difficult than the verbal working memory task, because in addition to a high amount of kilocalories, the composition of spirits is almost exclusively ethanol according to the United States Department of Agriculture (2019).
Remarkably, in all hierarchical regression models that turned out to be significant for total alcohol intake, quantity of alcohol intake, quantity of beer intake and total spirit intake, the influence of these variables on working memory performance was low, as indicated by ΔR2 values. All of these models explained less than 1% of the variance in working memory. This finding demonstrates that working memory variance is mostly explained by the demographic and biological variables controlled in the model and only slightly explained by alcohol intake.
In comparisons of the groups that drank mostly beer, wine, liqueur, or spirits with nondrinkers, beer drinkers outperformed drinkers of all other beverages and nondrinkers. Beer drinkers were also faster in the verbal and spatial working memory tasks than all other groups except for liqueur drinkers. Importantly, this finding was not influenced by participants’ age because across all decades, the consumption of beer, wine, liqueur and spirits was equivalent. We asked participants which type of alcoholic beverage they drank more often because most individuals drank several types of alcoholic drinks. The choice of a specific type of drink might be related to the social context, physical environment or emotional condition, among others. However, these specific situations occur occasionally; thus, it is highly likely that individuals who drink daily under similar conditions would choose to drink their preferred type of drink rather than another type of drink.
Beer (Chen & Blumberg, 2009) and wine (Markoski et al., 2016) are rich in polyphenols, such as flavonoids and resveratrol, which have potent antioxidant and anti-inflammatory properties. In the current study, beer showed stronger benefits for working memory than wine, which may be attributed to the additional nutrient components found in beer. Beer contains more protein, B vitamins and some minerals than wine (Sohrabvandi et al., 2012), which may explain the greater positive effects on working memory observed in beer drinkers. However, among all the additional compounds found in beer, vitamin B6 may have a more significant role because among 64 nutrients, vitamin B6 was one of the few nutrients that benefited working memory performance across the entire adult lifespan (Cansino et al., 2023).
Although beer has additional nutrients that increase its positive effects on working memory performance, the main beneficial effects should be attributed to its ethanol content because the memory effects of all these additional nutrients present in a variety of foods are not as evident as those of consuming alcoholic drinks. Across the adult lifespan, we found a descending trend in alcohol consumption. However, only individuals between 21 and 30 years old consumed more alcohol than individuals between 41 and 80 years old. Therefore, alcohol consumption remains quite stable across adulthood. Moreover, no preferred drink in a specific decade was identified because all types of drinks are consumed across the adult lifespan.
The dose‒response function indicates the expected discrimination level for verbal and spatial working memory for each amount of alcohol intake per week. The function reveals that for both memory processes, the optimal amount of alcohol is 100 g/w, which is approximately 7 drinks per week. This optimal amount applies to women and men because we estimated the dose‒response function after controlling for sex and the rest of the demographic and biological variables. This outcome concurs with several studies that concluded that moderate alcohol intake benefits cognition (Rehm et al., 2019). The estimated derivative function reveals that after 100 g/w of alcohol, the probability effects on memory become negative, with a sharper decrease at the beginning and an almost imperceptible decrease at the end, indicating that the treatment effect does not confer an additional decrease in either of the two types of memory. However, the critical amount of alcohol intake is approximately 350 g/w, which is equivalent to 25 drinks per week, because after this amount, memory performance starts to decline even more than that of whole-life abstainers.
Theoretical and practical implications
The present findings are significant because they contribute to unraveling the strong controversies surrounding an extensive research field that has been questioned for decades because of methodological weaknesses. By carefully selecting whole-life abstainers as the reference group, we were able to provide reliable evidence that habitual moderate alcohol intake, and above all, beer consumption, benefits verbal and spatial working memory discrimination and speed across the entire lifespan. Nevertheless, when several demographic and biological variables are controlled, the effects of moderate alcohol consumption benefit working memory discrimination but not speed. Moreover, the theoretical implications are robust because the benefits of moderate alcohol intake on human working memory extend previous findings in rats that identified that the moderate administration of alcohol has direct effects on brain regions that support working memory. The present study improves our knowledge of previous findings by showing the effects of moderate alcohol intake on the specific cognitive domain of working memory. These effects were observed for the first time on accurate measures of discrimination and speed in verbal and spatial working memory, revealing that the effects of alcohol consumption on memory are equivalent across the entire adult lifespan. This study also reports dose‒response curves that offer precise effects of each gram of alcohol intake per week on working memory.
The practical implications are important because it has traditionally been claimed that alcohol should be completely avoided to prevent health damage; however, we observed that across all adulthood, the consumption of moderate alcohol is habitual, and only 19.3% of participants distributed across all decades were abstainers. Moreover, participants of all ages drink all types of alcoholic beverages. These findings indicate that programs that encourage alcohol abstinence to preserve health or avoid serious consequences, such as alcohol dependency, have failed. Therefore, individuals should be more accurately informed about the specific amounts of alcohol intake that may cause no damage and even benefit some cognitive functions, such as memory. However, health advisors or society in general should not encourage drinking alcohol because each individual may have special health conditions or genetic features for which alcohol consumption could be associated with other consequences. Working memory and other types of memory are universal, i.e., their functioning is equal across all individuals. Likewise, alcohol has a universal physiological influence on body functioning. Therefore, although the present study was not planned to be representative of any specific population, the results obtained here might be applicable beyond the current sample.
Limitations and future directions
The present study has several limitations; one limitation is that participants’ reports of their alcohol consumption may be affected by inaccuracies or by social desirability bias. Nevertheless, these measurement errors are expected to be random. Despite this limitation, observational studies allow the examination of a variable in real-life situations, which is not possible in interventional experiments. Another limitation is that causality conclusions cannot be confirmed in a cross-sectional study. However, because we assessed participants’ alcohol intake patterns across their entire lives, we consider that the influence of previous and actual alcohol consumption on memory was reliably measured.
Future research should focus on assessing the effects of moderate alcohol consumption on other types of memory and on different cognitive domains to actually map whether alcohol has a general effect on cognition or whether its effects are selective. The employment of precise methods to measure each cognitive domain is strongly advised because several paper-and-pencil instruments do not examine pure processes and are less controllable. Observational studies are valuable to assess alcohol consumption in real-life conditions; however, alcohol intake measurement could be improved by requesting participants to report their consumption every day for a significant period to obtain more precise measurements. Moreover, reports could be highly specific to obtain information such as the type of drink, the drink brand, and the container employed to accurately estimate the amount of alcohol intake and its effects on cognition.
Conclusions
Discrimination and speed in verbal and spatial working memory among drinkers were superior to those among nondrinkers, a finding that supports one of our hypotheses. The direct effects of alcohol (increasing acetylcholine and NMDAR expression in brain regions crucial for working memory) may underlie the benefits of moderate alcohol consumption observed in the present study. Moreover, total alcohol intake over the lifespan and the amount of alcohol intake per week improved working memory discrimination after controlling for several demographic and biological variables. This outcome partially supports another of one our hypotheses, although we did not find significant effects of alcohol consumption on working memory speed. However, the significant influence of alcohol intake on working memory performance was small after controlling for several demographic and biological variables. Therefore, the effects of moderate alcohol consumption on working memory might be small in real-life conditions because all individuals possess varying combinations of demographic and biological factors.
Beer drinkers showed higher working memory discrimination levels and faster responses than nondrinkers and wine or spirits drinkers. This outcome contradicts our hypothesis that wine would have greater benefits for working memory performance. Although beer and wine are rich in antioxidants and anti-inflammatory components, beer also contains B vitamins and protein, which might explain its superior effects on working memory. We predicted a change in alcohol consumption across the adult lifespan; this hypothesis was supported for alcohol consumption in general but not for specific types of drinks. Only individuals between 21 and 30 years old drank more than individuals in other decades. Although the same amount of beer, wine, liqueur and spirits was consumed over the adult lifespan, there was a trend to drink less alcohol with increasing age. This outcome supports another one of our hypotheses. If alcohol consumption is so widely used at all ages, it is important to consistently inform people that only moderate alcohol consumption has benefits, as was observed for working memory, instead of promoting total abstinence, a goal that is difficult to achieve.
The dose‒response curves showed a U-shape, indicating that verbal and spatial working memory discrimination were higher in moderate alcohol drinkers than in abstainers and heavy drinkers, confirming another of our hypotheses. Consumption of up to 100 g of alcohol per week, which is equivalent to one drink per day, was the optimal amount of alcohol to enhance verbal and spatial working memory performance. Remarkably, this finding was observed after controlling for demographic and biological factors. The present study increases our understanding of the effects of alcohol consumption by specifically examining working memory across adulthood, extending findings mostly obtained for global cognition in older adults. Therefore, the results of the present study apply to individuals of all ages across the entire adult lifespan.
Data Availability
Data are available upon reasonable request.
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Funding
This work was supported by the National Autonomous University of Mexico, General Direction of Academic Personal Affairs (DGAPA) (grant numbers IN304202, IN300206, IN300309, ID300312, IG300115, IG300618, and IG300121).
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Selene Cansino wrote the manuscript and conceptualized and designed the study. Frine Torres-Tejo and Cinthya Estrada-Manilla performed the experiments. Cinthya Estrada-Manilla organized the database. Selene Cansino and Silvia Ruiz-Velasco analyzed the data. All authors contributed to the article and approved the submitted version.
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This study was approved by the Bioethics Committee of the School of Medicine at the National Autonomous University of Mexico. The experiments were performed in accordance with the Declaration of Helsinki. All of the participants provided informed consent.
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Cansino, S., Torres-Trejo, F., Estrada-Manilla, C. et al. Does habitual moderate alcohol consumption enhance working memory performance?. Curr Psychol 43, 13785–13801 (2024). https://doi.org/10.1007/s12144-023-05459-3
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DOI: https://doi.org/10.1007/s12144-023-05459-3