Alcohol Consumption and Cognitive Performance in the Framingham Heart Study
Transcript of Alcohol Consumption and Cognitive Performance in the Framingham Heart Study
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American Journal of Epidemiology
Copyright O 199 9 by The Johns Hopkins University School of Hygiene and Public Health
All rights reserved
\fol.150, No. 6
Printed inU S A
Alcohol Consumption and Cognitive Performance in the Framingham Heart
Study
Penelope K. Elias,
1
Merrill F. Elias,
2
Ralph B. D'Agostino,
1
Halit Silbershatz,
1
a nd P hilip A. Wolf
3
Recent studies have indicated that moderate alcohol intake may be beneficial to cognitive functioning in
women,
although not necessarily in me n. Data from the Framingham Heart Study, a large, prospective study of
cardiovascular disease in Framingham, Massachusetts, were used to examine the relation between alcohol
consum ption an d cogn itive ability. The major research question was whether a different alcohol-cognition
relation wo uld be found for male and female drinkers. Men (n = 733) and w omen (n =
1,053),
aged 55-88 years,
were qu eried as to their weekly intake of alcohol, and these data were used to construct groups of abstainers,
very light, light, moderate, and heavy drinkers. Data from earlier reports of alcohol consumption were also
examined. Participants were administered eight tests which reflect performance in the domains of verbal
memory, learning, visual organization and memory, attention, abstract reasoning, and concept formation.
Multivariate linear regression analyses were used with statistical adjustment for age, education, occupation,
cardiovascular diseas e, and associated risk factors. Wom en who drank m oderately (2 -4 drinks/day) showed
superior performance in many cognitive domains relative to abstainers. For men, superior performance was
found within the range of 4 -8 drinks/day, although fewer significant relations were observed. These results were
confirmed by prospective analyses of 24-year drinking history.
Am J Epidemiol
1999;150:580-9.
alcohol drink ing; cardiovascular diseases; cognition; men; risk factors; women
Early studies of the relation between moderate alco-
hol consumption and cognitive functioning (1-5) sup-
ported the notion that drinking at any level was associ-
ated with poorer performance on cognitive tests. This
research was conducted primarily with relatively small
samples of young to middle-aged male social drinkers.
However, two studies (4, 6) corroborated these results
for a subsample of women whose drinking patterns
(amount and frequency of consumption) were similar
to their male coun terparts.
Subsequent research with male and female college
students (7-9) and elderly men (10) led to the conclu-
sion that no significant negative relation exists
Received for publication March 2, 1998, and accepted for publi-
cation January 22, 1999.
Abbreviations: AC, attention and concentration composite; BMI,
body mass Index; Cl, confidence interval; CVD, cardiovascular dis-
ease; HDL-C, high density lipoprotein cholesterol; K-A, Kaplan-
Albert; LJM, Learning and Im mediate Mem ory composite; OR, odds
ratio.
1
Depa rtmen t of Math em atics, Statistics and Consulting Unit,
Boston University, Boston, MA.
2
Department of Psychology, University of Maine, Orono, ME.
3
Department of Neurology, Boston University School of Medicine,
and the Section of Preventive Medicine and Epidemiology, Evans
Memorial Department of Clinical Research and Department of
Medicine, Boston Medical Center, Boston, MA.
Reprint requests to Dr. Penelope K. Elias, Department of
Mathematics, Statistics and Consulting Unit, Boston University, 111
Cummington St., Boston, MA 02215.
between social drinking and level of cognitive func-
tioning. In fact, Bates and Tracy (11) reported that
increasing levels of alcohol use among young female
social drinkers were related to better performance on
many cognitive tests.
More recent studies with older samples have indi-
cated that a U- or J-shaped curve m ay best describe the
relation between level of alcohol consumption and
cognitive performance (12-16). Drinkers of low to
moderate amounts of alcohol performed at a higher
level than abstainers or heavy drinkers. However, in
one report (12), statistical control for age, income,
education, and gen der rendered the findings
nonsignif-
icant. In another study (16), the protective effects of
moderate consumption were limited only to those par-
ticipants who exhibited chnical conditions associated
with atherosclerosis.
It is especially important to examine data for men
and women separately when alcohol consumption is a
predictor variable, because their consumption levels
are very different. In virtually every study which
included both sexes, women consumed alcohol less
frequently and in smaller amounts than men (4, 6-8,
11-15,
17). The issue of sex differences in the relation
of alcohol consumption and cognitive performance
was addressed by Dufouil et al. (17), using data from
the Epidem iology of Vascular Aging (EVA) study. This
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Alcohol Consumption and Cognitive Performance 581
research included 574 men and 815 women, aged
59-71 years. No association between drinking and
cognition was found for the male participants; for the
female participants, moderate alcohol consumption
was associated with better performance on seven often
cognitive tests and an overall composite score.
Indeed, physiologic evidence also supports the strat-
egy of a priori gender stratification. Women are more
vulnerable than men to the adverse effects of heavy
alcohol consumption in terms of brain shrinkage (18).
At six drinks per day, women are at higher risk of
death from non-cardiovascular disease causes than
men (19). Moderate levels of alcohol consumption
also have decidedly different effects in men and
women, including effects on high density lipoprotein
cholesterol (HDL-C) levels (20, 21), hypertensive
blood pressures (22), and degree of peripheral arterial
disease (23). Regarding all-cause mortality, the benefi-
cial effects of alcohol occur at approximately two stan-
dard drinks per day less in women than in men (24).
The present study involved a large prospective, com-
munity-based sample of men and women who partici-
pated in the Framingham Heart Study from 1948 to
1976. From study inception, biennial physical exam ina-
tions were conducted for the purpose of assessing mor-
bidity and risk factors associated with cardiovascular
disease. At Exam s 14/15, a subset of study participants
was given a series of neuropsychological tests, the
Kaplan-Albert (K-A) battery. Previous studies with this
sample (25 ,26 ) indicated a positive association between
current amount of alcohol consumed on a weekly basis
and performance on the neuropsychological tests. The
present study was designed to explore more fully the
alcohol-cognition relation in the Framingham Heart
Study cohort Most importantly, we wished to examine
gender differences in the relation between current and
past drinking patterns and cognitive test performance.
MATERIALS AND METHODS
Study design
During Exam s 14 or 15 (19741976), participants in
the Framingham Heart Study were administered the
Kaplan-Albert (K-A) neuropsychological test battery
(27-3 0). The study cohort consisted of 2,123 subjects,
aged 55-89 years, who underwent neuropsychological
testing (75 percent of the potential subject pool). The
subjects who were not tested did not differ from the
study cohort in terms of age, sex, or education (25).
All participants were screened for cardiovascular
risk factors and events at the biennial examinations
and extensive medical histories were taken. Of the
2,123 eligible participants, 317 persons were excluded
based on the following criteria: 1) diagnosis of stroke
{n =122); 2) diagnosis of dementia n =12); 3) com-
pleted fewer than the eight subtests of the K-A battery
(n = 17 3); and 4) missing data for the predictor or con-
trol variables (n = 10). The present study sample con-
sisted of 1,806 individuals.
Measurement of alcohol consumption
At Exams 2, 7, 12, 13, 14, and 15, participants were
asked the following questions as part of the medical
history interview: 1) How man y bottles, cans, or
glasses of beer do you consume in a we ek? 2) How
many glasses of wine do you consume in a wee k? 3)
How many cocktails, highballs, or straight drinks do
you consume in a week ? This information w as used
to create a drinking variable measured in ounces of
pure alcohol consumed per w eek based on the follow-
ing conversion equation:
Drink (oz/week) = (0.57 x no. of cocktails) + (0.444
x no. of beers) + (0.4 x no. of glasses of wine).
The drink variable was used to define groups charac-
terized by level of current drinking: very light
drinkers, 3.5 oz/week (28
oz/week (>933 ml). Based on criteria established by
the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) (31), a drink was defined as
12 oz (355 ml) of beer, 5 oz (148 ml) of wine, or 1.5
oz (44 ml) of distilled spirits, each of which contains
approximately 0.5 oz (15 ml) of pure alcohol. Thus,
these groups may be described in terms of drinks/day:
very light drinkers, ^1 drink/day; light drinke rs, 1-2
drinks/day; moderate drinkers (>2 and Adrinks/day);
heavy drinkers (>4 and 8 drinks/day.
As in previous studies (4, 6-8, 11-15, 17), the dis-
tributions of male and female drinkers differed consid-
erably. Amounts of alcohol consumed in mean
oz/week were 5.0 6.5 for men (range, 0-45) and 1.8
3.0 for women (range, 0-23). Both distributions
were positively skewed, with only 10 men and no
women falling into the highest drinking category (very
heavy drinkers). Only nine women fell into the heavy
drinking category. It was decided to eliminate the very
heavy drinking category entirely, and, for the analyses
involving women, to also eliminate the heavy drinking
category. Thus, the final study sample consisted of 733
men and 1,053 women.
Finally, because previous research (32) had demon-
strated that recently abstinent alcohol abusers showed
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582 Elias et al.
cognitive impairment on some of the tests in the K-A
battery, we were concerned that the abstainer group
may have included some ex-heavy drinkers who might
bias our results. However, inspection of the data from
the previous exam ination (Exam 13, 2 years earlier)
revealed that in no case did a current abstainer report
heavy drinking at that time. Rather, all abstainers in
our cross-sectional analyses either never drank or
drank rightly to moderately in the 4 years prior to neu-
ropsychological testing.
Neuropsychological test battery
The K-A battery consists of eight subtests from the
Wechsler Adult Intelligence Scale (WAIS), the
Wechsler Memory Scale (WMS), and the Multilingual
Aphasia Examination (27). The tests were chosen to
sample cognitive performance in multiple domains,
including immediate and long-term verbal memory,
paired associates learning, visual organization and
memory, attention, abstract reasoning, and concept
formation (33). The K-A battery is sensitive to cogni-
tive decline with age, education, and cardiovascular
disease (2 7-3 0). Tests were presented in the following
standard sequence: Logical Memory-Immediate
Recall, Visual Reproductions, Paired Associates
Learning, Digit Span Forward, Digit Span Backward,
Word Fluency, Similarities, and Logical Memory-
Delayed Recall. The K-A battery takes approximately
30 minutes to administer.
The full sample m eans and standard deviations were
used to transform raw test scores to standardized z
scores. A total composite score, consisting of the aver-
age of thez scores obtained for each of the eight tests,
was also calculated for each individual. This score
reflected global test competence (27) and has been
used as the primary variable in studies of the effects of
age,
blood pressure, and type II diabetes on cognitive
performance in the Framingham Heart Study cohort
(25,
29, 30).
For the purpose of variable reduction and based on
the results of an earlier factor analysis of the K-A bat-
tery (28), two additional co mp osites were constructed.
The first composite is labeled Learning and
Immediate Memory (LIM) and is the average of the z
scores for Logical Memory-Immediate Recall +
Visual Reproductions + Paired Associates. This com-
posite reflects both immediate learning and secondary
memory processes (28). The second composite is
labeled Attention and Concentration (AC) and is the
average of Digit Span Forward + Digit Span
Backward. Although the AC composite involves
memory processes, it primarily reflects immediate
registration of information, attention, and passive
span of apprehension , as well as double tracking in
which memory and digit reversing are accomplished
simultaneously (28, 33).
Statistical control variables
Results of linear regression analyses were adjusted
for five statistical control v ariables. Three of the se vari-
ables were coded as is usual in studies involving the
Framingham data: age (in years at time of neuropsy-
chological testing); education (on a scale of 1-4, with
0-8 years = 1; 9-11 years = 2; 12 years = 3; and >12
years = 4); occupation (on a scale of 1-7, with execu-
tive/professional = 1; managerial = 2; administrative
personnel = 3; clerical and sales = 4; skilled manual
employee = 5; semi-skilled employee = 6; and
unskilled employee = 7). Gender was not included as a
control variable, because all analyses were done for
men and women separately, as explained below.
Because each participant in the Framingham Heart
Study had undergone a thorough physical examination
biennially since 1948, we were able to accurately
ascertain the presence of five risk factors for cardio-
vascular disease and six initial cardiovascular events.
Rather than test statistical models which included a
total of 14 control variables, we simplified the models
by designing two control variables which reflect the
extent of risk for cardiovascular disease and the occur-
rence of previous cardiovascular events.
A risk factor index was constructed as a scale (0-5)
with each risk factor coded 1 (present) or 0 (absent).
Each individual received a risk factor score based on
the sum of the five codes. The risk factors were deter-
mined as follows: 1) hypertension, defined as present
if systolic blood pressure was >140 mmHg or diastolic
blood pressure was ^90 mm Hg on each of two succes-
sive readings obtained by the clinic physician or the
individual was on antihypertensive medication; 2) dia-
betes mellitus, defined as present if non-fasting glu-
cose level was at least 11.11 mm ol/liter (200 mg/dL ) or
the individual was using insulin or an oral hypo-
glycemic agent on or before the K-A test; 3) smoking,
defined as present if
th
individual reported smoking at
least one cigarette per day during the past year, 4) high
body mass index (BMI), defined as present if BMI
(weight (kg)/height (m)
2
) was >29; 5) high total serum
cholesterol, defined as present if cholesterol levels
were >200 mg/dL (>5.20 mmol/liter).
Lastly, a statistical control variable was constructed
based on the presence or absence of cardiovascular
disease prior to K-A testing. Presence of cardiovascu-
lar disease was determined by a panel of three physi-
cians utilizing criteria published elsewhere (34). The
diseases represented by this variable included myocar-
dial infarction, angina p ectoris, coronary insufficiency,
intermittent claudication, congestive heart failure, and
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Alcohol Consum ption and Cognitive Performance 58 3
transient ischemic attack. The disease variable was
coded 1 (any of the diseases present) or 0 (all diseases
absent). It differed from the risk factor index in that it
was not cumulative. Thus, an individual who suffered
one cardiovascular event received a score of 1 as did
an individual who suffered >2 events.
Statistical analyses
The distributions for alcohol consum ption variables
differed substantially for men and women, the former
group drinking at a much higher level than the latter.
Thus, an a priori decision was made to analyze the
data for men and women separately. All analyses
employed a multivariate linear regression model.
Dependent variables included the three composite
scores (LIM, AC, and Total) and the three remaining
tests (Similarities, Word Fluency, and Delayed
M emo ry). Data were analyzed using the general linear
models procedure of the SAS statistical software
package (35).
For the analyses of current alcohol consumption
and cognitive performance, the independent variable
was level of drinking (drinking group). These analy-
ses closely paralleled methods used in recent studies
of alcohol consumption and cognition (e.g., 14, 17)
or cardiovascular disease (e.g., 44). Dummy vari-
ables were created to represent the alcohol consump-
tion groups for the men (very light, light, moderate,
and heavy) and women (very light, light, and moder-
ate).
Each individual was coded 0 or 1 to indicate his
or her group membership. In one set of analyses, the
referent group was abstainers; in another set of
analyses, abstainers were excluded and the referent
group was very light drinkers. All drinking level
groups were simultaneously entered into the regres-
sion model, along with the five control variables.
Thus, each drinking group was compared with the
abstainer or very light drinker groups with statistical
control for the other drinking groups and the control
variables.
For the analyses of past drinking levels and current
cognitive performance, the independent variable was
mean ounces of alcohol consumed per week, defined
as the sum of oz/week reported at Exams 2, 7, 12, and
13, divided by 4. Thus, this variable represents the
average oz of alcohol consumed per week over 24
years. Because neuropsychological testing began at
Exam 14, at least 2 years intervened between the final
alcohol measurement and cognitive assessment.
Finally, we conducted linear regression analyses
with each risk factor and cardiovascular disease vari-
able entered simultaneously and independently into
the statistical models rather than being included in
their respective disease indices. This procedure
yielded identical results to analyses employing the
indices and thus we report only the latter below.
RESULTS
Demographic characteristics for the men and
women are shown in table 1. The wom en were slightly
older and had a higher mean risk factor index com-
pared with men, specifically because of a higher inci-
dence of hypertension and higher cholesterol levels.
However, the proportion of the sample with type n
diabetes was lower among the women than among the
men. The women also had significantly less pre-exist-
ing cardiovascular disease than the men.
Table 2 shows the demographic characteristics for
each of the drinking groups for men and women sepa-
rately. For both men and wom en, mean level of drink-
ing decreased as age increased. Educational level was
higher among the groups that drank more heavily,
TABLE 1. Demographic characteristics of men and women In
the Framlngham Heart Study who took the Kaplan-Albert
Battery, Framlngham, Massachusetts, 1974-197 6
Characteristic Men n =733)
Women
n = 1,053)
p value*
Age (years), mean (SD t) 66.4(7.2) 67.5(7.4)
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al
TABLE 2 Covartates ofalcohol consumption among
men and
womenIn
the
Framlngham Heart Study who took
the
K aplan-Albert
Battery, Framlngham, Massachusetts, 1974-1976
M en
Age (years), mean(SDt)
Education, mean
(SD)$
Occupat ion, mean
(SD)
Alcohol oz/week,
U
mean(SD)
Risk factors, mean
(SD)
Hypertension(%)
TypeIIdiabetes(%)
Cigarette smoking(%)
High BM I t(%)
High cholesterol
(%)
Pre-existing CVDf
(%)tt
Women
Age (years), mean(SD)
Education, mean (SD)}:
Occupat ion, m ean
(SD)
Alcohol oz/week, mean
(SD)
Risk factors, m ean
(SD)
Hypertension(%)
TypeIIdiabetes(%)
Cigarette smoking(%)
High
BMI
(%)
High cholesterol
(%)
Pre-existing
CVD
(%)ft
Abstain
r=158
67.7
(8.0)
2.5(1.0)
4.4(1.6)
1.7(1.0)
46.8
10.1
26.6
20.3
65.2
29.7
n
=407
69.3
(7.7)
2.5(1.2)
4.4(1.5)
2.0
(1.0)
63.1
10.6
17.4
28.7
83.8
17.7
Very light
n
=
244
66.6
(7.3)
2.9(1.0)
3.9(1.6)
1.4(0.9)
. 1.6(0.9)
46.7
9.0
18.0
25.0
64.8
20.9
n
= 462
66.9
(7.0)
2.8(1.1)
4.0 1.5)
1.3(0.9)
1.8(0.9)
54.1
4.8
22.5
21.4
85.1
13.4
Light
n
137
66.8 (7.0)
2.9(1.1)
3.9(1.7)
5.1(1.1)
1.8(1.0)
48.2
12.4
20.4
27.7
70.8
24.1
n=99
66.3
(7.4)
3.2(1.0)
3.3(1.6)
4.7 (0.9)
1.8(0.8)
48.4
5.1
31.3
13.1
83.8
15.2
Moderate
n
137
64.8 (6.6)
2.9(1.0)
3.8(1.7)
9.6(1.8)
1.9 (0.9)
55.5
8.8
30.7
24.8
73.7
21.9
n
=
85
64.1
(5.7)
3.3(1.0)
3.8(1.5)
8.8(1.5)
1.9(0.8)
52.9
0.0
48.2
7 .1
83.5
7.1
Heavy
n
=
57
64.8 (5.6)
2.7(1.1)
4.2(1.5)
18.7(3.7)
1.9(0.1)
63.2
5.3
31.6
19.3
70.2
21.1
p value*
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Alcohol Consum ption and Cognitive Performance 58 5
TABLE 3. Results of linear regression analyses describing the relation between current level of alcohol consumption and
neuropsychological test performance on the Kaplan-Albert battery for participants In the Framlngham Heart Study, Framlngham,
Massachusetts, 1974-19761
Sex and test on
Kaplan-Albert battery
Men
Delayed Memory
Word Fluency
Similarities
LIM composite^
AC composite
Total composite^]
Women
Delayed Memory
Word Fluency
Similarities
LIM comp osite
AC composite
Total composite
Very light
3.5 oz/wk
P
0.0319
-0.0800
-0.0853
0.0727
-0.0945
-0.0122
0.0580
0.1072
0.1030
0.0454
0.0963
0.0619
SE
0.0949
0.0865
0.0822
0.0878
0.0972
0.0533
0.0603
0.0601
0.0552
0.0572
0.0629
0.0345
Ught
3.6-7 oz/wk
P
0.1278
0.0379
0.0489
-0.1113
-0.1479
0.0254
0.2044*
0.0926
0.1022
0.2543**
0.0590
0.1236*
SE
0.1079
0.0984
0.0935
0.0999
0.1105
0.0607
0.1000
0.0997
0.0914
0.0572
0.1043
0.0571
Moderate
7.1-14 oz/wk
P
0.2705
0.0984
0.0297
0.1902
-0.0279
0.0999
SE
* 0.1093
0.0997
0.0947
0.1012
0.1120
0.0615
0.3318** 0.1069
0.3839
0.2044
0.3414
0.2665
0.2512
* 0.1066
* 0.0978
** 0.1034
0.1115
** 0.0611
14.1
P
0.3423
0.1490
0.0596
0.1467
0.3085
0.1925
Heavy
-28 oz/wk
SE
0.1433
0.1307
0.1241
0.1326
0.1326
* 0.0805
*p
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58 6 Elias et al.
TABLE 4. R esults of linear regression analyses describing the relation between current level of alcohol
consumption and neuropsych ologlcal test performance on the Kaplan-Albert Battery for non-abstaining
participants In the Framlngham Heart Study, Framlngham, Massachusetts, 1974-19761
Sex and test on
Kaplan-Albert battery
Men
Memory Delayed
Word Fluency
Similarities
UM composite:}:
AC composite
Total compositefl
Women
Memory Delayed
Word Fluency
Similarities
LIM composite
AC composite
Total composite
Light
3.6-7 oz/wk
0.0928
-0 .1093
0.1282
0.0322
-0.0570
0.0331
0.1550
0.0004
0.0042
0.2134*
-0.0451
0.0657
SE
0.0992
0.0903
0.0849
0.0914
0.1089
0.0553
0.1013
0.0992
0.0859
0.0970
0.1031
0.0565
Moderate
7.1-14 oz/wk
P
0.2331*
0.1645
0.1003
0.1070
0.0557
0.1033
0.2969**
0.3050**
0.1120
0.3118**
0.1703
0.2064**
SE
0.1004
0.0914
0.0859
0.0925
0.1021
0.0560
0.1084
0.1063
0.0920
0.1038
0.1104
0 . 0 6 0 5
Heavy
14.1-28 oz/wk
P SE
0.2382* 0.1373
0.1932 0.1249
0.1019 0.1175
0.0672 0.1275
0.3532** 0.1021
0.1787* 0.0765
*p
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Alcohol Consum ption and Cognitive Performance 58 7
TABLE 5. Results of linear regression analyses describing the
relation between drinking history mean oz/week over 24
years) and neuropsychologlcal test performance on the
Kaplan-Albert Battery for participants in the Fram lngham
Heart Study, Framlngham, Massachusetts, 197 4-1976 *
Sex and test on
Kaplan-Albert Battery
Men (n = 741)
Delayed Memory
Word Fluency
Similarities
LIM composite^
AC composi te
Total compositeH
Women (n=
1,059)
Delayed Memory
Word Fluency
Similarities
LIM composite
AC composite
Total composite
P
0.0127
0.0071
-0.0018
-0.0031
0.0035
0.0022
0.0185
0.0298
0.0084
0.0215
0.0254
0.0165
SE
0.0058
0.0052
0.0050
0.0053
0.0059
0.0032
0.0096
0.0096
0.0088
0.0091
0.0100
0.0055
p value
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