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Alcohol Intake and Risk of Dementia

Alcohol Intake and Risk of Dementia

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Alcohol Intake and Risk of Dementia
 Jose A. Luchsinger, MD,
Ã
Ming-Xin Tang, PhD,
Ã
Maliha Siddiqui, MPH, Steven Shea, MD,
#
and Richard Mayeux, MD
Ã
§ 
#
OBJECTIVES:
To examine the association between intakeof alcoholic beverages and risk of Alzheimer’s disease (AD)and dementia associated with stroke (DAS) in a cohort of elderly persons from New York City.
DESIGN:
Cohort study.
SETTING:
The Washington Heights Inwood–ColumbiaAging Project.
PARTICIPANTS:
Nine hundred eighty community-dwell-ing individuals aged 65 and older without dementia atbaseline and with data on alcohol intake recruited between1991 and 1996 and followed annually.
MEASUREMENTS:
Intakeofalcoholwasmeasuredusinga semiquantitative food frequency questionnaire at base-line. Subjects were followed annually, and incident demen-tia was diagnosed using
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
, criteria and classifiedas AD or DAS.
RESULTS:
After 4 years of follow-up, 260 individualsdeveloped dementia (199 AD, 61 DAS). After adjusting forage, sex, apolipoprotein E (APOE)-
e
4 status, education,and other alcoholic beverages, only intake of up to threedaily servings of wine was associated with a lower risk of AD (hazard ratio
5
0.55, 95% confidence interval
5
0.34–0.89). Intake of liquor, beer, and total alcohol was notassociated with a lower risk of AD. Stratified analyses bythe APOE-
e
4 allele revealed that the association betweenwine consumption and lower risk of AD was confined toindividuals without the APOE-
e
4 allele.
CONCLUSION:
Consumption of up to three servings of wine daily is associated with a lower risk of AD in elderlyindividuals without the APOE
e
-4 allele.
J Am Geriatr Soc52:540–546, 2004.
Key words: dementia; Alzheimer’s; alcohol; wine; elderly
W
ith the aging of the population, the prevalence of dementia is expected to increase significantly. Thereis no established treatment or preventive measure fordementia,butdelayingits onsetcouldsignificantlydecreaseits prevalence, with important public health implications.
1
Moderate alcohol intake has been associated with adecreased risk of dementia, mostly in European studies,
2–5
and there are conflicting data on whether moderate alcoholintake or intake of particular alcoholic beverages is relatedto a decreased risk of dementia. There is a paucity of dataon the relationship between alcohol intake and the inci-dence of dementia in the elderly in the United States, whomay have drinking patterns different from Europeans. Thisstudy was designed to examine the association between theintake of different types of alcoholic beverages anddementia in a cohort of persons aged 65 and older fromnorthern Manhattan.
METHODSStudy Population
Participants in the Washington Heights–Inwood ColumbiaAging Project cohort were drawn by random sampling of 2,126 healthy Medicare beneficiaries aged 65 and olderresiding within a geographically defined area of northernManhattan.
6
At entry, each subject underwent a structuredin-person interview including an assessment of health andfunction, a standard medical history, a physical andneurological examination, and a neuropsychological bat-tery.
7
Subjects were recruited between 1991 and 1996 andfollowed annually, repeating the baseline examination ateach follow-up. A food frequency questionnaire wasadministered to 1,422 individuals between baseline andthefirstfollow-up examination.Ofthese 1,422individuals,230 were excluded because of prevalent dementia, 210because of loss to follow-up, and two because of missingdietary data. Thus, the analytic sample comprised 980
Support for this work was provided by grants from the National Institute of Aging(AG07232andAG07702),theCharlesS.RobertsonMemorialGiftforresearch on Alzheimer’s disease, the Blanchette Hooker RockefellerFoundation,andtheNewYorkCityCouncilSpeaker’sfundforPublicHealthResearch.Address correspondence to Richard Mayeux, MD, Gertrude H. SergievskyCenter, PH-19, 630 West 168th St. New York, NY 10032.E-mail: rpm2@columbia.eduFrom the
Ã
Taub Institute for Research of Alzheimer’s Disease and theAging Brain;
w
Gertrude H. Sergievsky Center;
z
Division of GeneralMedicine, Department of Medicine,
§
Department of Neurology, and
k
DepartmentofPsychiatry,CollegeofPhysiciansandSurgeons;Departmentsof 
z
Biostatisticsand
#
Epidemiology,JosephP.MailmanSchoolofPublicHealth,Columbia University, New York.
 JAGS 52:540–546, 2004
r
2004 by the American Geriatrics Society
0002-8614/04/$15.00
 
subjects. The 916 individuals excluded due to loss tofollow-up or no dietary information were older than thefinal sample (mean age
Æ
standard deviation
5
88.2
Æ
8.6vs 73.3
Æ
5.8) and had a similar proportion of women(70% vs 67%).
Diagnosis of Dementia and Cognitive Impairment
A group of neurologists, psychiatrists, and neuropsychol-ogists made a diagnosis of dementia and assignment of specific cause by consensus based on the informationgathered at the initial and yearly follow-up visits. Thediagnosis of dementia was based on
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
criteria
8
and required evidence of cognitive deficit on theneuropsychologicaltestbatteryandevidenceofimpairmentin social or occupational function; persons with a globalsummary score on the Clinical Dementia Rating (CDR) of 0.5 or more were considered to have dementia.
9
Diagnosisof Alzheimer’s disease (AD) was based on the NationalInstitute of Neurological and Cognitive Disorders andStroke
F
Alzheimer’s Disease and Related Disorders Asso-ciation criteria.
10
Diagnosis of dementia associated withstroke (DAS) was made in all subjects with a history of stroke. Because moderate alcohol intake is related to alower risk of stroke,
11
a less-conservative definition of DASwas used to avoid finding an association between alcoholand AD because of misclassification of DAS as AD. Brainimaging was available in 85% of cases of stroke; in theremainder,WorldHealthOrganizationcriteriawereusedtodefine stroke.
12
Subjects without dementia but with ahistory of stroke at the baseline examination were includedin the analyses. These criteria and diagnostic methods havebeen used extensively in analysis of data in this cohort.
Dietary Data
Dietary data were obtained using a 61-item version of Willett’s semiquantitative food frequency questionnaire(SFFQ)(ChanningLaboratory,Cambridge,MA).
13
Trainedinterviewers administered in English or Spanish the SFFQby telephone between the baseline and first follow-upexaminations.Thequestionnaireinquiredaboutservingsof beer, liquor, and wine by serving frequency; possibleanswers were one to three servings/month, one serving aweek, two to four servings a week, five to six servings aweek, one serving a day, two to three servings a day, four tofive servings a day, and more than six servings a day. Oneserving of beer was equivalent to 12 oz (12.8 g of alcohol),one serving of liquor was equivalent to 1.5 oz (14 g of alcohol), and one wine serving was equivalent to 4 oz (11 gof alcohol). In light of the possibility of nonspecific alcoholeffects and specific nonalcoholic effects of the differentbeverages, alcohol intake was examined in two ways: byexamining the association between beer, liquor, and wineservings separately with incident dementia and by examin-ing the association between total alcohol servings anddementia. Individuals were classified as nondrinkers (0servings reported), light drinkers (1 serving a month to 6servings a week), moderate drinkers (1 to 3 servings a day),and heavy drinkers (
4
3 servings a day); this classificationwas made trying to resemble previous publications in thisfield
2
for the sake of comparability and following theformat of the questionnaire. Because of a low number of moderate drinkers, the light and moderate drinkers wereaggregated in one category (1 serving a month to 3 servingsa day). Heavy alcohol intake was included despite the lownumber of individuals in this category because heavyalcohol intake may increase the risk of dementia.
14
SFFQshave been used and validated for the determination of nutrient intake in the elderly.
15–19
The validity of the foodfrequency questionnaire used in the Washington Heights–Inwood Columbia Aging Project cohort was assessed in asubsample of 78 individuals using two 7-day food recordsasthecriterion.Thecorrelationforenergy-adjustedalcoholintake was 0.44 (
P
o
.01) (M. Siddiqui, personal commu-nication, December 7, 2000). The reliability of the alcoholintake measure was compared between two SFFQs admi-nistered 2 months apart, and the measurements were notsignificantly different.
Definition of Covariates
Ethnic group was based on self-report using the format of the 1990 census.
20
Individuals were also asked whetherthey were of Hispanic origin. Participants were thenassigned to one of three groups: black (non-Hispanic),Hispanic, or white (non-Hispanic). Ethnic group was notfoundtosignificantlyalterthemodelsandwasnotincludedin the analyses. Data on years of education and heartdisease were also obtained by self-report. Education wasexamined as a continuous variable (education in years) andas a categorical variable (
6 years of education, 7–12 yearsof education, 13–16 years of education, and
4
16 years of education). Apolipoprotein (APO) genotype was deter-mined using the method of Hixson and Vernier.
21
Partici-pants were classified as positive for the APOE-
e
4 allelegenotype if they had one or two
e
4 alleles.
Data Analysis
Individuals were compared according to their beverageintake. Chi-square tests were used to compare sex, APOE-
e
4 status, and the presence of heart disease. Analyses of variance and
tests were used to compare mean age andnumber of years of education. Cox proportional hazardsregression was used for multivariate analyses, with thetime-to-event variable in the models specified as time frombaselineexaminationtoonsetofdementia.Individualswithdementia not caused by the subtype of interest werecensored at the time of onset of dementia. The final modelwas stratified by education category using the STRATAstatement in the SAS procedure PROC PHREG (SASInstitute, Inc., Cary, NC). Three types of analyses wereconducted: one in which servings of beer, liquor, and winewere related separately to dementia subtypes; another inwhich all beverage types were included in one model; andanother relating servings of total alcohol to dementia anddementia subtypes. Alcohol intake and other covariateswere treated as baseline time-constant covariates. Themultivariate model examining AD as an outcome includedage, sex, APOE-
e
4, and education as covariates, and themodels examining dementia and DAS as outcomes alsoincluded the presence of heart disease as a covariate.Inclusion of diabetes mellitus, hypertension, lipid levels,and smoking did not add predictive ability and were not
ALCOHOL INTAKE AND RISK OF DEMENTIA
541 JAGS APRIL 2004–VOL. 52, NO. 4
 
included in the final models. SAS version 7 for Windowswas used for all analyses (SAS Institute, Inc.).
RESULTS
The 980 individuals contributed 4,023 years of observation(mean observation time
5
4.1
Æ
1.5 years). The mean ageof the sample was 73.3
Æ
5.8, and 67% were women. Onehundred forty-four individuals reported beer intake (15%),138reportedliquorintake(14%),162reportedwineintake(17%), and 690 reported no intake of alcoholic beverages(70%). The incidence of AD was 4.9 cases per 100 person-years(199cases),andtheincidenceofDASwas1.5per100person years (61 cases).Table1showsthecomparisonofclinicalcharacteristicsamong different levels of intake for beer, liquor, and wine.Individuals with light to moderate intake of beer were lesslikely to be female (70.9% vs 46.0%;
P
o
.001) and haveheart disease (31.0% vs 18.7%;
P
5
.003) than subjectswho did not report drinking beer. Individuals with heavyintake were less likely to be female (70.9% vs 33.3%;
P
5
.044) than nondrinkers. Individuals who reported lightto moderate intake were less likely to be female (70.5% vs50.3%;
P
o
.001), had more years of education (9 vs 12years;
P
o
.001), and were less likely to have heart disease(30.6% vs 21.5%;
P
5
.008) than individuals who reportedno intake of liquor. Those who reported light to moderateintake of wine were less likely to be female (71.3 vs 42.0;
P
o
.001), had more years of education (9 vs 12;
P
o
.001),and were less likely to have heart disease (30.6 vs 19.6;
P
5
.019) than those who reported no wine intake. Similardifferences were observed for total alcohol intake.Analyses using multivariate proportional hazardsmodels examining the association between each alcoholicbeverage type individually and the outcomes of interestrevealed that only light to moderate intake of wine wassignificantly associated with a lower risk of incidentdementia (hazard ratio (HR)
5
0.64, 95% confidenceinterval (CI)
5
0.43–0.96;
P
5
.031) compared with indivi-duals who reported no wine intake. In similar analysesexamining AD as anoutcome (Table 2), a similarresult wasfound in a model adjusting for age and sex (HR
5
0.59,95% CI
5
0.38–0.91;
P
5
.018), but this association be-came nonsignificant after including education and APOE-
e
4 in the model (HR
5
0.69, 95% CI
5
0.45–1.09;
P
5
.118). Analyses examining dementia associated withstroke as an outcome (Table 3) showed that, in the fullmodel, the HR for light to moderate wine intake wassimilar to that in the previous analyses but not statisti-cally significant (HR
5
0.47, 95% CI
5
0.18,1.20;
P
5
.116). The analyses relating beer and liquor intakedid not reveal a significant association with any of theoutcomes.Analyses were conducted relating total alcohol intakein grams to dementia. Daily intake of alcohol in grams wascategorized to resemble the classification by servings usedfortheanalysesbybeveragetypeassumingthateachservingwasapproximately12gofalcohol:0g(nointake),0.1–36g(light to moderate intake), and more than 36 g (heavyintake). None of the HRs and CIs was suggestive of asignificant association between any level of alcohol intake
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542
LUCHSINGER ET AL.
APRIL 2004–VOL. 52, NO. 4 JAGS

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