To investigate whether coffee consumption is associated with 10-year cognitive decline in elderly men, as results of previous studies obtained hitherto have been controversial and prospective information on this association has been lacking.
Design, subjects and setting:
Six hundred and seventy six healthy men born between 1900 and 1920 from Finland, Italy and the Netherlands participated in a 10-year prospective cohort study. Cognitive functioning was assessed using the Mini-Mental State Examination (0–30 points, with a higher score indicating better cognitive performance). Coffee consumption was estimated in cups per day. A mixed longitudinal model was used to investigate the association between baseline coffee consumption and 10-year cognitive decline. Multiple adjustments were made.
Men who consumed coffee had a 10-year cognitive decline of 1.2 points (4%). Non-consumers had an additional decline of 1.4 points (P<0.001). An inverse and J-shaped association was observed between the number of cups of coffee consumed and cognitive decline, with the least cognitive decline for three cups of coffee per day (0.6 points). This decline was 4.3 times smaller than the decline of non-consumers (P<0.001).
Findings suggest that consuming coffee reduces cognitive decline in elderly men. An inverse and J-shaped association may exist between the number of cups of coffee consumed and cognitive decline, with the least cognitive decline for men consuming three cups of coffee per day.
Coffee is regularly consumed by millions of people around the world. Most citizens of Western countries start their day with a fresh cup of coffee. Owing to its caffeine content, coffee is the best known psychoactive stimulant worldwide (Fredholm et al., 1999) and directly improves cognitive performance (Lieberman et al., 2002). Besides this short-term effect, caffeine may also have long-term beneficial effects on brain function (Maia and de Mendonca, 2002).
Although some studies have shown inconsistent results regarding the effect of caffeine on cognition (Smith, 2002), results from cross-sectional studies provide some evidence that caffeine use (Riedel and Jolles, 1996) or coffee consumption as such (Jarvis, 1993) is associated with better cognitive functioning. A possible underlying mechanism could be that caffeine enters the bloodstream and acts as an antagonist on the A2a adenosine receptors in the brain, which consequently stimulates cholinergic neurons (Fredholm et al., 1999). Subsequently, these neurons protect against β-amyloid-induced neurotoxicity, a precursor of cognitive decline (Dall'Igna et al., 2003). If coffee consumption could delay cognitive decline, this could have major public health implications because cognitive decline is very common in the elderly.
Longitudinal studies investigating the association between coffee consumption and cognitive decline in the elderly are not available. A retrospective observational study found that lifetime coffee consumption was positively associated with cognitive performance in elderly women, but not in elderly men (Johnson-Kozlow et al., 2002). In the present study, we investigated the association between coffee consumption and 10-year cognitive decline in healthy elderly men in the Finland, Italy and The Netherlands Elderly (FINE) Study, a prospective European cohort study.
The study population consisted of men born between 1900–1920 of the Finnish, Italian and Dutch cohorts of the Seven Countries Study (Keys et al., 1966). Five hundred and twenty-three Finnish men were still alive in 1989, of whom 470 men (90%) were re-examined. In 1990, 718 Dutch men were still alive and 560 of them were re-examined (78%). Of the Italian cohorts, 493 men were still alive in 1991 and 391 (79%) were re-examined.
Men with a Mini-Mental State Examination (MMSE) score below 18 (n=118) (Murden et al., 1991; Tombaugh and McIntyre, 1992) or those whose age, coffee consumption, education, smoking status and alcohol consumption was unknown in 1990 were excluded (n=272). From the remaining 1031 men, subjects with diabetes (n=71) or a history of myocardial infarction (n=70), stroke (n=87), cancer (n=28) or more than one of these diseases (n=68) were excluded from the study population because these men could have changed their coffee consumption habits owing to their disease. Complete information on all possible confounding factors was available for 676 of these 707 men in 1990, of whom 101 were Finnish, 336 were Dutch and 239 were of Italian origin. Repeated examinations of the MMSE took place in 1995 (except for Finland) and 2000. More information about the study population has been described in detail elsewhere (Bijnen et al., 1996). All men were examined according to the international protocol used in the surveys of the Seven Countries Study (Keys et al., 1966). Approval of the Medical Ethics Committee in the different countries was obtained for each participating centre and participants have given their informed consent.
Information on the frequency of cups of coffee consumption in Finland and Italy was obtained with a standardized self-administered questionnaire (How much coffee do you consume on average each day? (expressed in number of cups per day)). In The Netherlands, this information was collected in a dietary survey in which a cross-check dietary history method was used (Kromhout et al., 1990). Participants were interviewed by a dietitian about their usual food consumption including coffee during the past 2–4 weeks. Both methods provided information about the usual coffee consumption per day during the past month. In Finland and Italy, participants reported the number of cups of coffee consumed per day. In The Netherlands, coffee consumption was coded in millilitre (ml) and converted into cups of coffee by assuming that one cup of coffee contained 125 ml. Coffee consumption was categorized into yes/no and into 0 to 4 and >4 cups of coffee per day. The correlation coefficient for coffee consumption in 1985 and 1990 ranged from 0.54 (P<0.001) for Finland till 0.72 (P<0.001) for The Netherlands.
Assessment of cognitive function
The MMSE was used to assess global cognitive function in each survey year (with the exception of the 5-year follow-up survey in Finland) and includes questions on orientation to time and place, registration, attention and calculation, recall, language and visual construction (Folstein et al., 1975). The MMSE was originally designed for clinical use, but is now extensively used in epidemiological studies and has proven to be a reliable and valid indicator of cognitive impairment with a good test–retest reliability (Siu, 1991; Launer, 1992; Tombaugh and McIntyre, 1992). Although the MMSE is a measure of global cognitive functioning and does not assess different cognitive domains in detail, it is sensitive enough to detect ‘clinically significant’ global cognitive decline (Lyketsos et al., 1999).
The MMSE score ranges from 0 to 30; a higher score indicates better cognitive performance. If a subject did not answer four or more individual items (of a total of 20), the total MMSE score was considered missing (n=6). If less than four items were missing, missing items were rated as zero and a total MMSE score was still calculated (Fillenbaum et al., 1988). In 1990, information on cognitive functioning of 676 Finnish, Italian and Dutch men was obtained. In 1995, 383 Italian and Dutch men participated in the survey and 285 Finnish, Italian and Dutch men in 2000.
Demographic and lifestyle information was obtained in all cohorts with standardized questionnaires. Education was assessed as the number of years of education. Height and weight were measured while men were wearing light clothing and no shoes. Body mass index was calculated by dividing weight by the square of height (kg/m2). Smoking status was categorized into non- and current smoker and alcohol consumption into consumers and non-consumers. Physical activity was assessed by a validated questionnaire designed for retired men (Caspersen et al., 1991). The total daily duration of physical activity was calculated and categorized into four groups: ⩽30, 31–60, 61–120 and >120 min/day. Information about the prevalence of diabetes and a history of myocardial infarction, stroke or cancer was obtained by questionnaires and validated with information from hospital registries or general practitioners.
Potential differences between consumers and non-consumers of coffee in each country were tested using analyses of variance or Student's t-test for normal distributed continuous variables, and Mann–Whitney U-test in case variables were not normally distributed. Categorical data were tested for difference with χ2test. Differences in continuous variables across coffee consumption categories were obtained by analyses of variance.
A general linear model was used to compare baseline cognitive functioning between coffee consumers and non-consumers in 1990. To determine the effect of baseline coffee consumption on 10-year cognitive decline a mixed longitudinal random coefficient model (SAS PROC MIXED procedure) was used, with the intercept and the time period as random effects. This procedure takes into account the intra-correlation of repeated measurements carried out at the same subject and does not exclude subjects with incomplete data at follow-up. Baseline coffee consumption (yes/no) was entered as a class variable in the model and the variable time as a continuous variable. To investigate whether 10-year cognitive decline differed between coffee consumers and non-consumers, the product of coffee consumption (yes/no) with time was included into the model. Cognitive decline (in points) for consumers and additional cognitive decline for the non-consumers (compared to the decline of the consumers) were given in the output of the programme.
Additional analyses regarding the association between the number of cups of coffee consumed and cognitive functioning were performed. Again, a general linear model was used to obtain baseline MMSE scores for each category and a mixed longitudinal random coefficient model for the cognitive decline per category. To test whether the association between the number of cups of coffee consumed per day and the magnitude of cognitive decline fits a parabolic function, we added the quadratic term of the number of cups of coffee consumed, to the model. Then we tested with the likelihood ratio test which model our data best fitted.
Adjustments were made for possible confounding factors age, education, country, alcohol consumption, smoking status and physical activity. Analyses assessing the 10-year cognitive decline between coffee consumption categories were additionally adjusted for baseline cognitive functioning. All statistical analyses were carried out using SAS software (version 8.2; SAS Institute Inc., Cary, NC, USA). Two-sided P-values of 0.05 or less were considered to be statistically significant.
Consumers and non-consumers
Table 1 displays the characteristics of consumers and non-consumers of coffee in Finland, Italy and The Netherlands. Overall, there were no differences in characteristics between consumers and non-consumers of coffee of each country, although Italian coffee consumers tended to be more physically active than Italian non-consumers.
Cognitive functioning in 1990s did not differ between men who consumed (25.7 points) and men who did not consume coffee (25.7 points, P=0.93), after adjustment for potential confounding factors Figure 1. However, men who consumed coffee had a 10-year cognitive decline of 1.2 points and men who did not consume coffee had an additional decline of 1.4 points (P<0.001). One hundred and nineteen men in the reference category of non-consumers were of Italian descent (82%). Despite this, even among only Italian coffee consumers and non-consumers, similar results were obtained. Baseline cognitive functioning of Italian coffee consumers (24.8 points) and non-consumers did not differ (25.0, P=0.5) and the 10-year cognitive decline of coffee consumers (1.7 points) and non-consumers (2.9 points) did differ (P=0.03). Italian non-consumers had an additional cognitive decline of 1.2 points, which was 0.2 points smaller than the additional decline of non-consumers of all three countries together.
Number of cups of coffee consumed
The number of cups of coffee consumed was inversely associated with age and positively with years of education and the percentage of smokers Table 2. Furthermore, Italian men drank less cups of coffee than men from Finland and The Netherlands. A linear trend was present for the number of coffee cups consumed and the unadjusted baseline cognitive test scores, with better cognitive functioning for men consuming more cups of coffee (P<0.0001). However, after adjustment for potential confounding factors this linear trend was no longer present (P=0.20).
Although baseline cognitive functioning did not differ among men who consumed 0, 1, 2, 3, 4 and >4 cups of coffee per day after adjustments, the 10-year cognitive decline did. An inverse and J-shaped association was present (tested with the likelihood ratio test), with the smallest 10-year cognitive decline for men consuming three cups of coffee per day (0.6 points) Figure 2. This decline is two points smaller compared to the decline of non-consumers (P<0.001). The decline of 1.6 points in men who consumed more than four cups of coffee was borderline significantly smaller (P=0.07) compared to men who did not consume coffee. Cognitive decline of men who consumed 1, 2, 3, 4 and >4 cups of coffee a day did not differ from each other (P>0.10).
The present study showed that coffee consumption was inversely associated with cognitive decline. Men who consumed coffee had a two times smaller 10-year cognitive decline than non-consumers. We also observed an inverse and J-shaped association between the number of cups of coffee per day consumed and 10-year cognitive decline, with the least decline for men consuming three cups of coffee per day.
Some methodological issues deserve to be discussed. Eighty-two per cent of the participants in the reference group of non-consumers were of Italian descent, whereas this percentage was only 23% in the consumers, therefore confounding by country may have influenced our results. However, this is less likely because the additional cognitive decline of the Finnish, Dutch and Italian non-consumers was even stronger than the additional cognitive decline of the Italian non-consumers only. Analyses regarding the dose–response relationship between coffee consumption and cognitive decline could not be performed in each country separately. About 50% of the Italian men did not drink coffee and the number of men in each category of coffee consumption in Finnish and Dutch men was too low for meaningful analyses. It is unlikely that a substantial number of elderly men in the three countries consumed decaffeinated coffee. However, if that is the case, the observed association between coffee consumption and cognitive decline would have been underestimated if caffeine is the responsible agent for this association.
Our overall results suggest an inverse and J-shaped association. This association was also present when analysing the association between mean coffee consumption of 1985 and 1990 and subsequent cognitive decline, which confirms the inverse and J-shaped association using the 1990 data only. However, the cognitive decline of men who consumed 1, 2, 3, 4 or more than 4 cups of coffee was not statistically different from each other. Therefore, more research is needed to investigate the dose-response relationship between coffee consumption and cognitive decline.
High drop-out rates owing to non-response or death may have caused selection bias. To reduce this effect, a mixed longitudinal random coefficient model was used. This procedure takes into account the intra-correlation of at least two measurements performed by the same subject and does not exclude subjects with incomplete data at follow-up. In spite of the high drop-out, analyses with only coffee consumers and non-consumers who participated until 2000 confirmed our results. In addition, analyses regarding the number of cups of coffee consumed among survivors tended also to an inverse and J-shaped (nonsignificant) association, despite the small number of survivors in each category.
Men with an MMSE score in 1990 below 18 (n=118) were excluded from our study population as these men had already an impaired cognition at baseline and therefore they could have made mistakes when reporting the number of cups of coffee consumed. Additional analyses in which we also included men with a chronic disease at baseline and men with missing values on possible confounding factors at baseline confirmed the results found in the present study among apparently healthy participants. Therefore, the results obtained in the present study can be generalized to the general population. However, men with an impaired cognition at baseline did not participate in the present study, therefore, the results of the present study are particularly generalizable to Western European men with an intact cognition while reporting the number of cups of coffee consumed. Results of other prospective studies on coffee consumption and cognitive decline are not available. Furthermore, coffee consumption behaviour may differ between men and women. Therefore, owing to the lack of data, it is not possible to answer the question whether results of our study can be generalized to women.
We used the MMSE to assess global cognitive functioning. Although the MMSE is a screening test, it is a reliable and valid indicator of cognitive impairment and has a good test–retest reliability and is often used in epidemiological studies (Siu, 1991; Launer, 1992; Tombaugh and McIntyre, 1992). A limitation of the MMSE is that it measures global cognitive functioning and does not assess specific cognitive domains in detail. Therefore, future studies should include a more extensive cognitive test battery and should focus on specific cognitive domains, for example, memory, concentration, attention, learning, language and visual construction. Furthermore, the MMSE is not sensitive enough to detect mild cognitive impairment and to discriminate among cognitively intact and mildly cognitively impaired persons (Tombaugh and McIntyre, 1992). However, with the MMSE it is possible to detect ‘clinically significant’ global cognitive decline (Lyketsos et al., 1999). In the present study, differences in baseline cognitive functioning could not be detected between cognitively impaired and cognitively intact persons in the cross-sectional analyses, as these persons were mildly or not cognitively impaired. During the follow-up period, when cognitive impairment increased, differences in cognitive decline among different categories of coffee consumers could be detected. Furthermore, the use of repeated measurements reduces the measurement error in the longitudinal analyses.
Coffee consumption was assessed with a self-administered questionnaire, which could have caused reporting bias. Men could have over-reported or under-reported their actual intake of coffee. An influence of this bias on the results regarding coffee or non-coffee consumption and cognitive decline does not seem likely. Also, men who were severely cognitively impaired at baseline were excluded from our study population and the question regarding coffee consumption was based on current and not on past coffee intake. Information on coffee consumption for the present study population was also collected in the three countries in 1985. The correlation between the amount of cups of coffee consumption in 1985 and 1990 ranged from 0.54 for Finland to 0.72 for the Netherlands. This indicates that the reported amount of cups of coffee consumption was not only an indicator of the number of cups of coffee consumed at the baseline survey but also suggests that the relative position in the distribution of coffee consumers was rather stable over time. Presumably, habitual coffee consumption was responsible for the effect observed in the present study.
The major strengths of this study are its longitudinal design and the opportunity to adjust for several possible confounding factors. No other study had ever investigated this association prospectively among healthy elderly and results of earlier reported epidemiological studies have limitations. The Rancho Bernardo Study showed with a retrospective design that lifetime coffee consumption was associated with better cognitive functioning among women but not among men (Johnson-Kozlow et al., 2002). The Canadian Study of Health and Aging showed that participants who consumed coffee nearly every day had a lower risk of becoming afflicted with Alzheimer's disease (Lindsay et al., 2002). The Health and Lifestyle survey showed that the more cups of coffee that were consumed the better the cognitive functioning. However this study was cross-sectional (Jarvis, 1993). In contrast to the previous results, the present longitudinal study shows that coffee consumption compared to no coffee consumption is associated with a smaller 10-year cognitive decline.
Coffee is a major source of caffeine and one cup of coffee contains about 85 mg of caffeine, almost twice the caffeine content of tea (∼45 mg). Caffeine seems to be the major component in coffee that could be responsible for the inverse association between coffee consumption and cognitive decline. Caffeine intake has been related to a lower risk of Alzheimer's disease (Maia and de Mendonca, 2002) and it may improve cognitive functions like memory, learning, vigilance and mood (Lieberman et al., 2002). On the other hand, some studies reported that caffeine intake was not associated with cognitive change (van Boxtel et al., 2003) or showed inconsistent results (Smith, 2002; Lorist and Tops, 2003).
A possible mechanism underlying the association between caffeine intake and cognitive functioning comes from animal experiments. Research with mice showed that while drinking coffee, caffeine enters the bloodstream and acts as an antagonist on the A2a adenosine receptors in the brain (Fredholm et al., 1999). Subsequently, this stimulates the secretion of cholinergic neurotransmitters (like acetylcholine), which in turn prevents β-amyloid-induced neurotoxicity in cerebellar neurons (Dall'Igna et al., 2003). Precise neuronal cellular mechanisms are not yet known and the generalizability of animal research to humans has its limitations. Furthermore, some animal studies suggest that the A2a adenosine receptor has an effect on the memory part of the brain, the hippocampus (Kopf et al., 1999).
Besides caffeine, coffee contains many other substances, like magnesium and many phenolic acids, of which chlorogenic acid is the most abundant one (Nardini et al., 2002). Consumption of coffee increases the antioxidant capacity in plasma (Natella et al., 2002; Svilaas et al., 2004), which may provide a protective effect against free radicals that cause oxidative damage to neurons, which appear to be very vulnerable to the effects of free radicals (Christen, 2000).
Our study showed that among elderly men coffee consumption was associated with a smaller cognitive decline compared to non-consumers. Consuming three cups of coffee per day was associated with the smallest cognitive decline. Because of the worldwide use of coffee, the increasing ageing of populations and related cognitive decline and because coffee consumption is a modifiable lifestyle habit, the results of the present study could have important public health implications if confirmed in other prospective studies. However, because coffee could also cause adverse health effects, prudence is called for when consuming too much coffee.
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The FINE Study is a part of the HALE project (Healthy Ageing: Longitudinal study in Europe) and supported by a grant from the European Union (QLK6-CT-2000-00211) to D Kromhout.
Guarantor: B van Gelder.
Contributors: All authors have contributed substantially to conception and design of the study, or analyses and interpretation of the data. They approved the final version and will take public responsibility for the content of this paper. There are no conflicts of interest with other organizations:BM van Gelder prepared part of the database, analyzed the data, and wrote the draft of the paper. B Buijsse, M Tijhuis and S Kalmijn contributed to the data analysis and drafting of the paper. S Kalmijn, S Giampaoli, A Nissinen and D Kromhout all contributed to the data collection. S Giampaoli, A Nissinen and D Kromhout are principal investigators of the FINE study in respectively Italy, Finland and The Netherlands. D Kromhout contributed to the drafting of the paper. All authors contributed to the final version of the paper and gave their approval to publish this final version.
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van Gelder, B., Buijsse, B., Tijhuis, M. et al. Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study. Eur J Clin Nutr 61, 226–232 (2007). https://doi.org/10.1038/sj.ejcn.1602495
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