Content uploaded by Brian Buijsse
Author content
All content in this area was uploaded by Brian Buijsse on Sep 04, 2014
Content may be subject to copyright.
ORIGINAL ARTICLE
Coffee consumption is inversely associated with
cognitive decline in elderly European men: the FINE
Study
BM van Gelder
1
, B Buijsse
2,3
, M Tijhuis
1,{
, S Kalmijn
4
, S Giampaoli
5
, A Nissinen
6,7
and
D Kromhout
3
1
Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment, Bilthoven, The
Netherlands;
2
Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands;
3
Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands;
4
Julius Centre for Health Sciences and Primary
Care, University Medical Centre Utrecht, Utrecht, The Netherlands;
5
National Institute of Health, Rome, Italy;
6
National Public Health
Institute, Helsinki, Finland and
7
Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland
Objective: 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.
Results: 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 (Po0.001). 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 (Po0.001).
Conclusions: 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.
European Journal of Clinical Nutrition (2007) 61, 226–232. doi:10.1038/sj.ejcn.1602495; published online 16 August 2006
Keywords: coffee; cognition; elderly; epidemiology
Introduction
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
Received 19 September 2005; revised 21 April 2006; accepted 23 May 2006;
published online 16 August 2006
Correspondence: B van Gelder, Centre for Prevention and Health Services
Research, National Institute for Public Health and the Environment, PO Box 1,
3720 BA Bilthoven, The Netherlands.
E-mail: Boukje.van.Gelder@rivm.nl
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.
{
Deceased 9 November 2005
European Journal of Clinical Nutrition (2007) 61, 226–232
&
2007 Nature Publishing Group All rights reserved 0954-3007/07 $
30.00
www.nature.com/ejcn
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 A
2a
adenosine receptors in the
brain, which consequently stimulates cholinergic neurons
(Fredholm et al., 1999). Subsequently, these neurons protect
against b-amyloid-induced neurotoxicity, a precursor of
cognitive decline (Dall’Igna et al., 2003). If coffee consump-
tion 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.
Methods
Study population
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 ¼ 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 ¼ 272). From the
remaining 1031 men, subjects with diabetes (n ¼ 71) or a
history of myocardial infarction (n ¼ 70), stroke (n ¼ 87),
cancer (n ¼ 28) or more than one of these diseases (n ¼ 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.
Coffee consumption
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 consump-
tion 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
44 cups of coffee per day. The correlation coefficient
for coffee consumption in 1985 and 1990 ranged from
0.54 (Po0.001) for Finland till 0.72 (Po0.001) 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 ¼ 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.
Other variables
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
Coffee consumption and cognitive decline
BM van Gelder et al
227
European Journal of Clinical Nutrition
dividing weight by the square of height (kg/m
2
). 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: p30, 31–60, 61–120 and
4120 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.
Statistical analyses
Potential differences between consumers and non-consu-
mers 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 w
2
test. 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 long-
itudinal 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 function-
ing 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 associa-
tion 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.
Results
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 ¼ 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 (Po0.001). 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 ¼ 0.5) and the 10-year cognitive
decline of coffee consumers (1.7 points) and non-consumers
(2.9 points) did differ (P ¼ 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 (Po0.0001). However,
after adjustment for potential confounding factors this linear
trend was no longer present (P ¼ 0.20).
Although baseline cognitive functioning did not differ
among men who consumed 0, 1, 2, 3, 4 and 44 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
(Po0.001). The decline of 1.6 points in men who consumed
more than four cups of coffee was borderline significantly
Coffee consumption and cognitive decline
BM van Gelder et al
228
European Journal of Clinical Nutrition
smaller (P ¼ 0.07) compared to men who did not consume
coffee. Cognitive decline of men who consumed 1, 2, 3, 4
and 44 cups of coffee a day did not differ from each other
(P40.10).
Discussion
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 decaffei-
nated 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 analys-
ing 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
Table 1 Selected characteristics of the study population at baseline, stratified by country and coffee consumption (n ¼ 676)
Characteristics Finland The Netherlands Italy
Non-consumers
(n ¼ 10)
Consumers
(n ¼ 91)
P
a
-value Non-consumers
(n ¼ 16)
Consumers
(n ¼ 320)
P
a
-value Non-consumers
(n ¼ 119)
Consumers
(n ¼ 120)
P
a
-value
Demographics
Age (mean (s.d.), years) 75.9 (5.2) 74.9 (4.4) 0.50 75.7 (5.1) 75.7 (4.3) 0.99 77.4 (4.0) 76.7 (3.5) 0.16
Education (mean (s.d.),
years received)
5.0 (2.9) 4.0 (2.5) 0.24 11.0 (2.5) 10.3 (4.3) 0.33 4.8 (2.7) 5.1 (2.5) 0.50
BMI (mean (s.d.), kg/m
2
) 28.3 (4.3) 26.1 (3.9) 0.10 25.4 (2.9) 25.8 (3.0) 0.63 25.9 (3.6) 26.5 (3.6) 0.17
Lifestyle
Cigarette smokers (numbers (%)) 0 (0) 10 (11) 0.59 2 (13) 75 (23) 0.31 18 (15) 26 (22) 0.19
Alcohol consumers (numbers (%)) 9 (90) 77 (85) 1.00 10 (63) 242 (76) 0.24 99 (83) 95 (79) 0.43
Leisure time physical activity
(mean (s.d.), min/week)
910 (1652) 622 (575) 0.60 609 (223) 636 (544) 0.35 698 (732) 883 (791) 0.063
Cognitive functioning
Unadjusted MMSE score
(mean (s.d.))
25.3 (3.9) 25.4 (3.1) 0.90 26.9 (2.2) 26.4 (2.3) 0.35 24.9 (2.9) 24.9 (2.7) 0.94
Adjusted MMSE score
(means (s.e.))
b
25.1 (0.93) 25.5 (0.30) 0.69 26.7 (0.52) 26.4 (0.12) 0.53 25.0 (0.23) 24.8 (0.23) 0.48
Abbreviations: MMSE, Mini-Mental State Examination; s.d., standard deviation; s.e., standard error.
a
P-value for difference between coffee consumers and non-consumers based on Student’s t-test, w
2
test, Fisher’s exact test or co-variance analysis.
b
Adjusted for age (continuous), education (continuous), cigarette smoking (yes/no), alcohol use (yes/no) and physical activity (categorical).
21
22
23
24
25
26
1990 2000
Stud
y
-
y
ears
MMSE-score
Consumers
Non-consumers
*
Figure 1 Coffee consumption at baseline and subsequent 10-year
cognitive decline in European elderly men. Adjustments were made
for age, education, country, alcohol consumption, smoking status
and physical activity. In analyses regarding cognitive decline, also
adjustments for baseline cognitive functioning were made. *Cogni-
tive decline of consumers is significantly different from non-
consumers (Po0.001).
Coffee consumption and cognitive decline
BM van Gelder et al
229
European Journal of Clinical Nutrition
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 relation-
ship 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 ¼ 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
Table 2 Baseline characteristics of the study population according to categories of coffee consumption
Characteristics Categories of daily coffee consumption P-value
for trend
a
0 cups
n ¼ 145
1 cups
n ¼ 133
2 cups
n ¼ 107
3 cups
n ¼ 105
4 cups
n ¼ 85
44cups
n ¼ 101
Country
Finland (no.) 10 1 13 14 34 29
Italy (no.) 119 85 23 10 0 2
The Netherlands (no.) 16 47 71 81 51 70
Demographic variables
Age (mean (s.e.), years) 77.2 (0.4) 77.1 (0.4) 75.7 (0.4) 75.6 (0.4) 75.2 (0.5) 74.8 (0.4) o0.0001
Education (mean (s.e.), years received) 6.6 (0.3) 6.9 (0.3) 8.4 (0.3) 8.5 (0.4) 7.6 (0.4) 7.7 (0.4) o0.0001
BMI (mean (s.e.), kg/m
2
) 25.9 (0.3) 26.2 (0.3) 25.7 (0.3) 25.8 (0.3) 26.2 (0.4) 26.1 (0.3) 0.90
Lifestyle
Cigarette smokers (%) 16 17 19 16 18 33 0.001
Alcohol consumers (%) 80 75 84 76 77 81 0.79
Leisure time physical activity (mean (s.e.), min/week) 689 (56) 687 (57) 681 (64) 717 (65) 658 (72) 718 (66) 0.97
Cognitive functioning
Unadjusted MMSE score (mean (s.e.)) 25.3 (0.2) 25.1 (0.2) 26.0 (0.3) 26.1 (0.3) 26.0 (0.3) 26.2 (0.3) o0.0001
Adjusted MMSE score (mean (s.e.))
b
25.7 (0.2) 25.4 (0.2) 25.7 (0.2) 25.8 (0.2) 25.8 (0.3) 26.0 (0.2) 0.20
Abbreviations: BMI, body mass index; MMSE, Mini-Mental State Examination; s.e., standard error.
Values are percentages of participants, unless otherwise indicated.
a
Linear trend for associations with coffee consumption based on a general linear model, obtained by analyses of variance.
b
Adjusted for age (continuous), education (continuous), country, cigarette smoking (yes/no), alcohol use (yes/no) and physical activity (categorical).
-3
-2.5
-2
-1.5
-1
-0.5
0
01234>4
Cognitive decline
Decline
*
*
*
**
Cups of coffee a day
Figure 2 Magnitude of 10-year cognitive decline by number of
cups of coffee consumed at baseline. Multivariate adjusted for age,
education, country, alcohol consumption, smoking status, physical
activity and baseline cognitive functioning. *Significant different
from 0 cups of coffee a day (Po0.05). **Significant different from 0
cups of coffee a day (Po0.001).
Coffee consumption and cognitive decline
BM van Gelder et al
230
European Journal of Clinical Nutrition
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, concen-
tration, attention, learning, language and visual construc-
tion. 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 con-
sumption 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 respon-
sible 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 partici-
pants 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 (B45 mg). Caffeine seems to be the major
component in coffee that could be responsible for the
inverse association between coffee consumption and cogni-
tive 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 A
2a
adenosine receptors in the brain
(Fredholm et al., 1999). Subsequently, this stimulates the
secretion of cholinergic neurotransmitters (like acetylcho-
line), which in turn prevents b-amyloid-induced neurotoxi-
city 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 A
2a
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).
Conclusion
Our study showed that among elderly men coffee consump-
tion 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
Coffee consumption and cognitive decline
BM van Gelder et al
231
European Journal of Clinical Nutrition
adverse health effects, prudence is called for when consum-
ing too much coffee.
Acknowledgements
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.
References
Bijnen FC, Feskens EJ, Caspersen CJ, Giampaoli S, Nissinen AM,
Menotti A et al. (1996). Physical activity and cardiovascular risk
factors among elderly men in Finland, Italy, and the Netherlands.
Am J Epidemiol 143, 553–561.
Caspersen CJ, Bloemberg BP, Saris WH, Merritt RK, Kromhout D
(1991). The prevalence of selected physical activities and their
relation with coronary heart disease risk factors in elderly men:
the Zutphen Study, 1985. Am J Epidemiol 133, 1078–1092.
Christen Y (2000). Oxidative stress and Alzheimer disease. Am J Clin
Nutr 71, 621S–629S.
Dall’Igna OP, Porciuncula LO, Souza DO, Cunha RA, Lara DR (2003).
Neuroprotection by caffeine and adenosine A2A receptor blockade
of beta-amyloid neurotoxicity. Br J Pharmacol 138, 1207–1209.
Fillenbaum GG, George LK, Blazer DG (1988). Scoring nonresponse
on the Mini-Mental State Examination. Psychol Med 18,
1021–1025.
Folstein MF, Folstein SE, McHugh PR (1975). ‘Mini-mental state’. A
practical method for grading the cognitive state of patients for the
clinician. J Psychiatr Res 12, 189–198.
Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE (1999).
Actions of caffeine in the brain with special reference to factors
that contribute to its widespread use. Pharmacol Rev 51, 83–133.
Jarvis MJ (1993). Does caffeine intake enhance absolute levels of
cognitive performance? Psychopharmacology (Berlin) 110, 45–52.
Johnson-Kozlow M, Kritz-Silverstein D, Barrett-Connor E, Morton D
(2002). Coffee consumption and cognitive function among older
adults. Am J Epidemiol 156, 842–850.
Keys A, Aravanis C, Blackburn HW, Van Buchem FS, Buzina R,
Djordjevic BD et al. (1966). Epidemiological studies related to
coronary heart disease: characteristics of men aged 40–59 in seven
countries. Acta Med Scand Suppl 460, 1–392.
Kopf SR, Melani A, Pedata F, Pepeu G (1999). Adenosine and memory
storage: effect of A(1) and A(2) receptor antagonists. Psychophar-
macology (Berlin) 146, 214–219.
Kromhout D, Nissinen A, Menotti A, Bloemberg B, Pekkanen J,
Giampaoli S (1990). Total and HDL cholesterol and their correlates
in elderly men in Finland, Italy, and The Netherlands. Am J
Epidemiol 131, 855–863.
Launer LJ (1992). Overview of incidence studies of dementia
conducted in Europe. Neuroepidemiology 11 (Suppl 1), 2–13.
Lieberman HR, Tharion WJ, Shukitt-Hale B, Speckman KL, Tulley R
(2002). Effects of caffeine, sleep loss, and stress on cognitive
performance and mood during US Navy SEAL training. Sea-Air-
Land. Psychopharmacology (Berlin) 164, 250–261.
Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB et al.
(2002). Risk factors for Alzheimer’s disease: a prospective analysis
from the Canadian Study of Health and Aging. Am J Epidemiol 156,
445–453.
Lorist MM, Tops M (2003). Caffeine, fatigue, and cognition. Brain
Cogn 53, 82–94.
Lyketsos CG, Garrett E, Liang KY, Anthony JC (1999). Cannabis use
and cognitive decline in persons under 65 years of age. Am J
Epidemiol 149, 794–800.
Maia L, de Mendonca A (2002). Does caffeine intake protect from
Alzheimer’s disease? Eur J Neurol 9, 377–382.
Murden RA, McRae TD, Kaner S, Bucknam ME (1991). Mini-Mental
State exam scores vary with education in blacks and whites. JAm
Geriatr Soc 39, 149–155.
Nardini M, Cirillo E, Natella F, Scaccini C (2002). Absorption of
phenolic acids in humans after coffee consumption. J Agric Food
Chem 50, 5735–5741.
Natella F, Nardini M, Giannetti I, Dattilo C, Scaccini C (2002). Coffee
drinking influences plasma antioxidant capacity in humans.
J Agric Food Chem 50, 6211–6216.
Riedel WJ, Jolles J (1996). Cognition enhancers in age-related
cognitive decline. Drugs Aging 8, 245–274.
Siu AL (1991). Screening for dementia and investigating its causes.
Ann Intern Med 115, 122–132.
Smith A (2002). Effects of caffeine on human behavior. Food Chem
Toxicol 40, 1243–1255.
Svilaas A, Sakhi AK, Andersen LF, Svilaas T, Strom EC, Jacobs Jr DR
et al. (2004). Intakes of antioxidants in coffee, wine, and
vegetables are correlated with plasma carotenoids in humans.
JNutr134, 562–567.
Tombaugh TN, McIntyre NJ (1992). The Mini-Mental State Examina-
tion: a comprehensive review. J Am Geriatr Soc 40, 922–935.
Van Boxtel MP, Schmitt JA, Bosma H, Jolles J (2003). The effects of
habitual caffeine use on cognitive change: a longitudinal perspec-
tive. Pharmacol Biochem Behav 75, 921–927.
Coffee consumption and cognitive decline
BM van Gelder et al
232
European Journal of Clinical Nutrition