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Hi All,

Alcohol benefits brains, says the pdf-available article discussed

and presented below. The full article is last.

C B C . C A N e w s - F u l l S t o r y :

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Drink a day protects aging brain, women's study shows

Last Updated Wed, 19 Jan 2005 20:54:05 EST

CBC News

TORONTO - Older women who enjoy having a glass of wine with dinner

or an occasional nightcap may be helping to prevent the onset of

dementia, a new study suggests.

As part of the ongoing Nurses' Health Study, researchers in the

U.S. looked at almost 12,500 women between the ages of 70 and 81 for

up to 15 years.

Low-to-moderate consumption of alcohol shows health benefits.

The team tracked the women's alcohol consumption, and tested their

memory and concentration. The study appears in Thursday's issue of

The New England Journal of Medicine.

Researchers found women who drank an average of one drink per day

had a 20 per cent lower risk of cognitive impairment, compared to

nondrinkers.

Drinking less than 15 grams of alcohol per day in wine, beer and

spirits all showed benefits.

Doctors who study Alzheimer's and other forms of dementia say it

makes sense that alcohol protects the brain since it's been shown to

protect the heart.

One theory suggests alcohol improves blood flow to both organs.

" There's a lot of evidence now that the same kind of things that

are good for your overall cardiovascular system are good for your

brain as well, " said the study author and epidemiologist Francine

Grodstein of Brigham and Women's Hospital in Boston.

But it's impossible to say for sure that it's the alcohol alone

that helps cognitive abilities based on an observational study like

this one.

The study's authors aren't sure that having more than one drink a

day is beneficial since there weren't enough women in the study

drinking that much to draw conclusions.

The findings probably apply to men as well as women, although

other studies with more measurements over time are needed.

The take-home message is, " If you would like to enjoy a glass of

red wine with your dinner go ahead and enjoy it, " said Carol

Greenwood, a nutritional scientist at Toronto's Baycrest Centre.

In an editorial accompanying the study, Dr. Denis and

Bienias said those seeking to " maximize cognition in old age " should

keep in mind the harmful effects of alcohol abuse.

For those who can't drink alcohol or prefer not to, experts say

diet and exercise can be just as beneficial for the heart and, by

extension, the brain.

This week in New Engl J Med, 352 (3) Jan 20, 2005

Effect of Moderate Alcohol Consumption on Cognitive Function in

Women

The adverse effects of excess alcohol intake on cognitive function

are well established, but the effect of moderate alcohol consumption

is uncertain. This study assessed cognitive function in relation to

alcohol intake among women in the Nurses' Health Study who were 70 to

81 years of age and then reassessed it two years later.

The data suggest that up to one drink per day does not impair

cognitive function and may actually decrease cognitive decline.

Related Editorial

New Engl J Med, 352, Jan 20 (3) 2005 289-290

Alcohol Consumption and Cognition

Denis A. , M.D., and L. Bienias, Sc.D.

Related Article by Stampfer, M. J.

Loss of cognitive function in old age, especially severe cognitive

loss due to Alzheimer's disease, is a serious public health problem

that will only increase as the number of people in the oldest age

groups increases in the United States and other developed countries.

Effective preventive measures are the key to coping with this

potentially overwhelming problem as it emerges and are even more

important than is treatment of affected persons. Unfortunately, very

few effective means of either prevention or treatment have been

identified to date.

Studies that provide clues about prevention are therefore welcome.

In this issue of the Journal, Stampfer et al.1 report that as

compared with abstinence, low-to-moderate consumption of alcohol was

associated with better cognition both cross-sectionally and over time

in a study that involved more than 11,000 U.S. nurses. Consumption of

1.0 to 14.9 g of alcohol per day, or about one drink per day or less,

was associated with a reduced risk of cognitive impairment (relative

risk as compared with abstinence, 0.85; 95 percent confidence

interval, 0.74 to 0.98). The women's cognitive status was

characterized in terms of both their cross-sectional performance on

brief telephone tests of cognitive function and the difference in

results between tests administered an average of 1.8 years apart.

The investigators clearly recognized the importance of prevention

by focusing on the relation of a modifiable everyday behavior to the

preservation of cognitive function in later life. They examined this

relation in a large, longitudinal observational study — the Nurses'

Health Study — and considered alcohol consumption over a long period,

up to 15 years. Cognitive function was assessed by a telephone

interview, a fairly new technique, but there is little suggestion

that the use of this technique underestimated cognitive decline

because of undue loss of impaired subjects on repeated testing.

Overenthusiasm for a potentially preventive measure, however, can

be risky, and as with all studies, this report has important

limitations that we must recognize and understand. The use of an

observational study to provide information on the relation of a

lifestyle variable or a health habit to cognition presents difficult

and complex challenges, especially when that potentially beneficial

habit is alcohol consumption. Low-to-moderate alcohol consumption has

previously been linked to several positive health outcomes, most

convincingly to a decreased risk of coronary heart disease,2 but

alcohol abuse is also linked to a wide range of health and social

problems according to both common knowledge and formal study.3

Two limitations of the present report deserve particular

attention. The first is the direction of the observed association.

This study examined whether light-to-moderate alcohol consumption was

related to a change in cognitive function. We must recognize,

however, that older persons who are in good cognitive and physical

health may be more likely than less healthy peers to indulge in low-

to-moderate alcohol consumption as part of their social activities.

Precise information about older people is limited, but persons who

consume moderate amounts of alcohol appear, on average, to have more

favorable general health and social characteristics than abstainers.4

Although the observed relation between alcohol and cognition

persisted after Stampfer et al. adjusted their analyses for a number

of social and health characteristics, demonstrating that the changes

in cognition are actually attributable to alcohol consumption is

impossible in an observational study.

A second and perhaps more important limitation is complex and

concerns meaningful measurement of cognition as an outcome. As

already noted, Stampfer et al. assessed cognition in two ways, cross-

sectionally and as change over time. Assessment of cognition at a

single point in time, as in a cross-sectional analysis, is very

likely not an informative means of examining cognitive impairment

among older persons. Education and culture strongly influence the

results of cognitive testing and may also be related to health habits

such as alcohol consumption in subtle, difficult-to-measure ways.

Among older persons, however, the educational and cultural factors

that influence the results of cognitive testing are usually constant

over time. To the extent that this is true, these factors influence

the measurement of cognition at each point in time, but they do not

influence the change in results over time for each person. Thus, a

change in results is a far more meaningful measure of cognition than

is cross-sectional testing.

One must estimate how well Stampfer et al. were able to assess

changes in cognitive function over time. The authors attempted to do

so by setting a standard for impaired test performance at the second

measurement and including the baseline level of performance as a

predictor in the model. Unfortunately, the intuition that one can

fully assess change as an outcome and distinguish it from the initial

level of performance on the basis of measurements at only two times

is misleading, since any difference between performance at two points

in time necessarily reflects much of the initial cross-sectional

level.5 A model assessing change from measurement at three or more

times6,7 can adjust for this problem by allowing simultaneous but

separate estimation of the level and the change over time and can

more accurately distinguish factors associated with the level of

cognitive performance (e.g., cultural influences) while empirically

testing whether other factors of interest (e.g., alcohol consumption)

are related to a change in cognitive performance.

The prevention of cognitive decline in old age as well as the

conditions underlying it is one of the major public health challenges

of the 21st century. Few things are as valuable as the unimpaired

ability to reason. In the light of the importance and complexity of

the issue, what can readers reasonably conclude about the relation

between mild-to-moderate alcohol consumption and cognition? The

report by Stampfer and colleagues represents an incremental advance

but necessarily leaves a substantial residue of uncertainty. We must

await future studies, preferably population-based, that combine the

strengths of the present investigation — large size, rigorous

conduct, and measurement of the exposure over a long period — with

measurement of cognition at a sufficient number of points in time to

ensure that we are actually examining changes in cognition. In the

meantime, persons seeking to maximize cognition in old age must keep

in mind both the uncertainty of the current results and the knowledge

that alcohol consumption can be a double-edged sword, with the

dangers of overindulgence being all too familiar.

References

Stampfer MJ, Kang JH, Chen J, Cherry R, Grodstein F. Effects of

moderate alcohol consumption on cognitive function in women. N Engl J

Med 2005;352:245-253.[Abstract/Full Text]

Stampfer MJ, Colditz GA, Willett WC, et al. A prospective study of

moderate alcohol consumption and the risk of coronary disease and

stroke in women. N Engl J Med 1988;319:267-273.[Abstract]

10th Special report to the U.S. Congress on alcohol and health:

highlights from current research. Bethesda, Md.: National Institute

on Alcohol Abuse and Alcoholism, June 2000.

Fillmore KM, Golding JM, Graves KL, et al. Alcohol consumption and

mortality. I. Characteristics of drinking groups. Addiction

1998;93:183-203.[CrossRef][iSI][Medline]

Rogosa D, Brandt D, Zimowski M. A growth curve approach to the

measurement of change. Psychol Bull 1982;92:726-748.[CrossRef][iSI]

Laird NM, Ware JH. Random-effects models for longitudinal data.

Biometrics 1982;38:963-974.[iSI][Medline]

Diggle P J, Heagerty P, Liang K-Y, Zeger SL. Analysis of longitudinal

data. 2nd ed. New York: Oxford University Press, 2002.

New Engl J Med, 352 (3) Jan 20, 2005, 245-253.

Effects of Moderate Alcohol Consumption on Cognitive Function in

Women

M. J. Stampfer, Jae Hee Kang, Sc.D., Chen, M.P.H.,

Cherry, M.D., and Francine Grodstein

ABSTRACT

Background The adverse effects of excess alcohol intake on cognitive

function are well established, but the effect of moderate consumption

is uncertain.

Methods Between 1995 and 2001, we evaluated cognitive function in

12,480 participants in the Nurses' Health Study who were 70 to 81

years old, with follow-up assessments in 11,102 two years later. The

level of alcohol consumption was ascertained regularly beginning in

1980. We calculated multivariate-adjusted mean cognitive scores and

multivariate-adjusted risks of cognitive impairment (defined as the

lowest 10 percent of the scores) and a substantial decline in

cognitive function over time (defined as a change that was in the

worst 10 percent of the distribution of the decline). We also

stratified analyses according to the apolipoprotein E genotype in a

subgroup of women.

Results After multivariate adjustment, moderate drinkers (those who

consumed less than 15.0 g of alcohol per day [about one drink]) had

better mean cognitive scores than nondrinkers. Among moderate

drinkers, as compared with nondrinkers, the relative risk of

impairment was 0.77 on our test of general cognition (95 percent

confidence interval, 0.67 to 0.88) and 0.81 on the basis of a global

cognitive score combining the results of all tests (95 percent

confidence interval, 0.70 to 0.93). The results for cognitive decline

were similar; for example, on our test of general cognition, the

relative risk of a substantial decline in performance over a two-year

period was 0.85 (95 percent confidence interval, 0.74 to 0.98) among

moderate drinkers, as compared with nondrinkers. There were no

significant associations between higher levels of drinking (15.0 to

30.0 g per day) and the risk of cognitive impairment or decline.

There were no significant differences in risks according to the

beverage (e.g., wine or beer) and no interaction with the

apolipoprotein E genotype.

Conclusions Our data suggest that in women, up to one drink per day

does not impair cognitive function and may actually decrease the risk

of cognitive decline.

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Habitual excess alcohol intake impairs the brain,1 but the effect

of moderate consumption is unclear. A cognitive benefit from moderate

alcohol intake is plausible, given the strong link between moderate

alcohol intake and the decreased risk of cardiovascular disease2,3;

cognitive impairment and cardiovascular disease share common risk

factors.4 In addition, Ruitenberg et al. reported that moderate

alcohol consumption was related to a decreased risk of both vascular

and nonvascular dementia5 and proposed that moderate alcohol

consumption may increase the release of brain acetylcholine. Most

studies,6,7,8,9,10,11,12,13,14,15 but not all,16,17,18 have tended to

show that moderate drinkers do better on cognitive tests than

nondrinkers; however, few studies have had samples that were large

enough to yield statistically significant results or to assess long-

term, stable patterns of alcohol intake and very early signs of

cognitive decline. Also, many studies have been limited by inadequate

control for confounding, and none have examined specific alcoholic

beverages. We addressed these issues in the Nurses' Health Study.

... Mini–Mental State Examination (MMSE). ... we constructed

separate regression models for alcohol from beer, white wine, red

wine, and spirits and controlled for alcohol from the other sources

within each level of total alcohol intake.

In regression models, we considered the following potential

confounding variables, possibly related to both cognitive function

and alcohol intake: age at the time of the interview (continuous);

highest educational degree (registered nurse or associate's degree,

bachelor's degree, or graduate degree); a history of hypertension,

high cholesterol levels, diabetes, or heart disease (yes vs. no);

level of physical activity, measured in metabolic-equivalent hours

per week (quintiles); age at menopause; use of postmenopausal hormone

therapy (current, past, or never); use of vitamin E supplements (yes

vs. no); body-mass index (the weight in kilograms divided by the

square of the height in meters [less than 22.0, 22.0 to 24.9, 25.0 to

29.9, or 30.0 or more]); cigarette-smoking status (current, past, or

never); aspirin use (once or twice per week, three or more times per

week, or none); ibuprofen use (yes vs. no); scores for the mental

health index ...

Results

In this cohort, 51 percent of the women were nondrinkers, 44 percent

drank 1.0 to 14.9 g of alcohol per day (up to about one drink), and 5

percent consumed 15.0 to 30.0 g per day. Health and lifestyle

characteristics generally did not vary substantially according to

alcohol intake (Table 1).

Women consuming less than 15.0 g of alcohol per day tended to have

slightly better mean cognitive scores than nondrinkers (Table 1).

After adjustment for potential confounding factors, such women had

significantly better mean cognitive scores than nondrinkers on all

three primary outcomes (Table 2 and Figure 1). We found no

significant differences in cognitive performance between nondrinkers

and those drinking 15.0 to 30.0 g of alcohol per day, although the

size of the latter group was small (648 women). For the TICS, each

additional year of age was associated with a mean difference of 0.15

point; thus, for participants who were 70 to 81 years of age,

drinking 1.0 to 14.9 g of alcohol per day was cognitively equivalent

to being approximately a year and a half younger (mean difference,

0.21; range, 0.11 to 0.30).

Women who drank less than 15.0 g of alcohol per day had a risk of

cognitive impairment that was approximately 20 percent lower than

that among nondrinkers (Table 2), with and without adjustment for

confounders, which was statistically significant for all three

primary outcomes. For example, for the global cognitive score, women

who drank 1.0 to 14.9 g of alcohol per day had an adjusted relative

risk of cognitive impairment of 0.81 (95 percent confidence interval,

0.70 to 0.93), as compared with nondrinkers.

Although we measured cognitive decline over a short period (mean,

1.8 years), women who drank 1.0 to 14.9 g of alcohol per day had a

lower risk of substantial cognitive decline during this period than

did nondrinkers (Table 3). The findings were statistically

significant for the TICS score and the verbal memory score.

For women who drank 1.0 to 14.9 g of alcohol per day, as compared

with nondrinkers, each type of beverage was significantly associated

with a lower risk of cognitive impairment, with relative risks

according to the global cognitive score ranging from 0.68 for beer to

0.84 for red wine. All the confidence intervals for specific

beverages broadly overlapped. When we analyzed the likelihood of a

substantial decline in cognitive function, the results were similar

to those for baseline analyses, with no marked differences according

to the type of beverage.

Finally, excluding women with diabetes from the analysis did not

change the results. Also, we found no material interactions between

alcohol intake and the apolipoprotein E 4 allele. With respect to the

global cognitive score, the relative risk of cognitive impairment

among moderate drinkers, as compared with nondrinkers, was 0.84 (95

percent confidence interval, 0.59 to 1.21) among those without the 4

allele and 0.84 (95 percent confidence interval, 0.46 to 1.53) among

those with the allele.

Discussion

We found that older women who consumed up to one drink per day had

consistently better cognitive performance than nondrinkers. Overall,

as compared with nondrinkers, women who drank 1.0 to 14.9 g of

alcohol per day had a decrease in the risk of cognitive impairment of

about 20 percent. Moreover, moderate drinkers were less likely to

have a substantial decline in cognitive function over a two-year

period. We found similar inverse associations for all types of

alcoholic beverages.

Our study had several limitations. We could not assess the effect

of high levels of alcohol intake, since there were few heavy drinkers

in our cohort. Also, cognitive decline was assessed only over a two-

year interval; thus, the association between alcohol consumption and

longer-term cognitive decline could not be evaluated. Information on

alcohol consumption was self-reported, perhaps leading to some

misclassification. However, our assessment of alcohol intake was

validated on the basis of dietary records and levels of biochemical

markers and has been used to predict several disease outcomes in this

cohort.34,35

Our telephone assessment of cognitive function may also have

resulted in some misclassification. However, we found that this

approach has high rates of reliability and validity in comparison

with in-person assessments. Furthermore, using results from the

telephone assessment method, we have observed strong associations

with established predictors of cognitive function (age, level of

education, and apolipoprotein E genotype); the magnitude of these

associations is similar to that reported with the use of in-person

cognitive interviews,27,30 further confirming the validity of our

methods. Misclassification of alcohol intake or cognition would tend

to result in an underestimate of the associations.

We cannot exclude the possibility that women with poor cognition

decreased their alcohol intake (reverse causation). This seems

unlikely, however, since we specifically excluded heavier drinkers

and limited our analyses to those with stable patterns of alcohol

intake. Finally, there may be uncontrolled confounding. Moderate

drinkers had several favorable health characteristics that may

influence cognitive function, such as a decreased incidence of

diabetes. However, analyses that excluded women with diabetes yielded

similar results. Adjustment for many potential confounders had little

effect on the results, suggesting that confounding is unlikely to

explain the observed associations. The finding of similar effects for

each alcoholic beverage also lends support to a causal interpretation

of the association, since patterns of confounding tend to differ

according to the type of beverage. Nonetheless, we cannot rule out

the possibility of confounding by unmeasured factors.

Our observations are generally similar to those in previous

studies of alcohol intake and cognitive function. Such studies were

all substantially smaller than ours and often showed nonsignificant

inverse relations. Two small studies16,17 showed no correlation

between the level of alcohol consumption and cognitive function, but

four others showed nonsignificant trends toward better cognitive

scores among moderate drinkers.6,7,8,9 Three large cross-sectional

studies of U.S. blacks,10 French men and women,12 and Japanese

Americans36 all showed significantly better cognitive performance

among moderate drinkers than among nondrinkers. Similar results were

obtained in five prospective studies.11,14,15,37,38 In a study of 333

men, Launer et al.13 reported that the prevalence of cognitive

impairment was significantly lower among men with moderate alcohol

intake than among nondrinkers, but alcohol intake was not associated

with cognitive decline, perhaps owing to the small sample.

Several studies showed an apparently stronger association between

alcohol intake and cognitive function among women than among men.

This difference may reflect a true effect of sex or perhaps less

misclassification of moderate alcohol consumption among women.

Several mechanisms have been proposed to explain the association of

moderate alcohol consumption with better cognition. The most

plausible relates to the consistently lower rates of cardiovascular

disease among moderate alcohol drinkers in many studies.2,3 This risk

reduction has been attributed partly to alcohol-induced elevations in

HDL cholesterol and reductions in fibrinogen and other thrombotic

factors.3 Thus, moderate intake of alcohol may also help preserve

brain vasculature, may prevent subclinical strokes, and could thus

result in better cognitive function. In support of this concept,

Mukamal et al.39 found that among older persons without

cerebrovascular disease, those with moderate alcohol intake had fewer

white-matter abnormalities and infarcts on magnetic resonance imaging

than nondrinkers. The same authors found pronounced reductions in the

risk of both vascular dementia and Alzheimer's disease among persons

consuming one to six drinks per week.40

Several studies have assessed whether there is an interaction

between alcohol intake and the apolipoprotein E genotype. Ruitenberg

et al.5 reported a stronger inverse association between the level of

alcohol intake and the risk of dementia among persons with the

apolipoprotein E 4 allele than among those without this allele,

although the difference between the groups was not significant;

Mukamal et al. reported the opposite trend.40 Conflicting findings

were also reported for cognitive decline.28,29 On the basis of these

results and our finding of no interaction between alcohol intake and

the apolipoprotein E 4 genotype, any pronounced interaction seems

unlikely.

Although the adverse effects of excessive alcohol intake are well

known and caution should be exercised in recommending even moderate

alcohol intake, our results combined with those of other studies

suggest that women who consume up to one drink per day have less

cognitive impairment and better cognitive function than nondrinkers.

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