alcohol consumption and cognitive performance in the framingham heart study

8/11/2019 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

58 0

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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

Am J Epidemiol Vol. 150, No. 6, 1999


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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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584 Eliaset

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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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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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


9/10


10/10

Alcohol Consu mption and Cognitive Performance 58 9

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