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[This following was written 14 Oct 2004 and posted on behalf of the original authors]

All:

RD wrote:

> http://www.scienceblog.com/community/article3928.html
>
> Frequent alcohol drinking in middle age harms the brain
>
> Frequent alcohol drinking in midlife is linked to mild mental (cognitive) impairment in old age, claims a study in this week's BMJ.
>
>Participants who drank no alcohol and those who drank alcohol
>frequently (several times a month) were both twice as likely to
>have mild cognitive impairment in old age than those who drank infrequently (less than once a month).

> The risk of dementia is also higher with heavier drinking, but only among those carrying a particular gene (apolipoprotein e4 allele) a known genetic risk factor for dementia.

---------------

[This refers to (0)].

> What I found surprising, is their definition of "frequent" as several times a month, while "infrequent" as LESS than once a month. ... How can there be such a dramatic effect from less than 12 drinks a year?? If you drink at all, seems to me a few drinks a month ("frequent" in their book!), say, one drink a week ..., or say 3 a week, I'd think physiologically you are a light/moderate drinker.
>
> Now, I'd expect damage from heavy drinking - but from light/moderate? Surprising. ... And then, I'm damaging my brain with NO drinks. Only with LESS than one drink a month (some 11 times a year!) do I not damage my brain. That's why they say "lies, damn lies and statistics".
>
> My take from this is that alcohol simply damages the brain in any quantity - if it can do so with consumption being as little as 1 time a month, then it is a brain damaging substance, period. So how to explain the artifact that NO drinking also is bad, while 11 drinks a year are "good"?

I agree that this result seems extremely surprising -- so I went digging on PubMed. The search:

Alcoholic Beverages AND dementia

... yielded 20 hits. Throwing out the articles with no abstracts, or which were about alcohol use amongst the already-demented, left 8 articles (0-7). Of these, all but (3,5) are prospective epidemiology. (3) says that "moderate consumption of wine was associated with a lower risk of developing AD. This result remains unchanged after adjustment for many potential confounders. The association between moderate alcohol consumption and risk of developing a dementia or AD was recently confirmed by prospective studies. In some studies, wine consumption was more specifically associated with a decreased risk, whereas beer or spirit consumption was not associated."

This appears to accurately summarize the available data: most studies do show a protective effect of alcohol, or of only wine, or of alcohol & esp wine; (0) showed an increased risk for total alcohol (4) found a reduction for wine but an increase for beer, and (6) was ambiguous: "While moderate wine consumption was found to be associated with a fourfold diminishing of the risk of Alzheimer's disease (OR = 0.26), as found in other studies, this effect was found to disappear when institutionalization was taken into account. Wine consumption was associated with an increased risk of decline over time in attention and in secondary memory."

Skimming thru' (0) I found in their Discussion: "the U shaped relation we found between alcohol consumption and mild cognitive impairment has also been found in other populations with respect to their different drinking patterns and different alcohol levels." Now, of course, their U shape is pretty bizarre, as Robert notes; fortunately, in following up on these studies, their categorization seems mor reasonable.

Their first reference is actually not very relevant; the next ( 8 ) found that "Compared with nondrinkers, the risk of a poor CASI score was lowered by 22% to 40% among men who consumed 1-60 ounces of alcohol per month." The next (9) found that "Alcohol use was associated with significantly less cognitive decline in alcohol drinkers when compared with nondrinkers for both sexes" but "When adjusted, a trend toward significantly less cognitive decline was seen in women drinkers, but not in men. Among female users, there was a trend toward less cognitive decline in women who used alcohol habitually as compared with those who were nonusers or heavy users. The authors conclude that, over long time periods, alcohol use is not associated with cognitive decline and, in women, may be associated with less decline."

(10) reports that "one to three drinks per day was significantly associated with a lower risk of any dementia (hazard ratio 0.58 ...) and vascular dementia (hazard ratio 0.29 ...]). We found no evidence that the relation between alcohol and dementia varied by type of alcoholic beverage."

(11) reports that "light to moderate drinking was significantly associated with a decreased risk of incident dementia and Alzheimer's disease compared with nondrinking (adjusted relative risk 0.5 ...). In the analysis of the subpopulation [of those with baseline Mini-Mental State Examination score > or =24], however, the inverse association ... was less evident and no longer statistically significant."

(12) briefly states that "wine consumption ... were associated with a reduced risk of Alzheimer's disease."

The optimal dose is not clearly resolved, but there is a trend: most studies where the dose is identified (2,6,7) fpund a risk reduction for ~ 3 glasses of wine/d; (1) says the reduction was for "moderate drinkers," & of course as we see in (0) this can be defined somewhat arbitrarily, but as these are French investigators I'm going to guess that it means at LEAST 1 glass/d & more likely a few. Again, ( 8 ) found 1-60 oz of alcohol/mo protective. (4), however, found the reduction for "Monthly and weekly intake of wine" but no change in risk for daily consumers vs teetotalers.

> Mostly, what I take away from this, is how useless are studies where there are such huge numbers of confounding factors. One can't really conclude anything.

One can & should take confounders into account, tho' in this case it doesn't seem to've clarified matters: (0) adjusted for age, sex, and education, along with "variables related with midlife alcohol drinking frequency (midlife body mass index, total cholesterol concentration, smoking status (smoker or non-smoker), and follow up time) and for other vascular factors (midlife systolic and diastolic blood pressure, history of myocardial infarction and stroke at follow up)." In light of the apparent special effect of wine, it seems more important that they did not distinguish between kinds of alcohol.

Above all, I think that rather it says we have to be cautious about looking at only 1 study.

The evidence on alcohol & dementia shows a clear trend toward a protective effect, most clearly for wine; while this alone would not convince me to take up drinking, the evidence for other positive health outcomes -- most notably, for total mortality -- is now piled up to the point where I'm quite seriously considering a daily glass of red wine.

-MR


0: Anttila T, Helkala EL, Viitanen M, Kareholt I, Fratiglioni L, Winblad B,
Soininen H, Tuomilehto J, Nissinen A, Kivipelto M.
Alcohol drinking in middle age and subsequent risk of mild cognitive impairment
and dementia in old age: a prospective population based study.
BMJ. 2004 Sep 4;329(7465):539. Epub 2004 Aug 10.
PMID: 15304383 [PubMed - indexed for MEDLINE]

1: Larrieu S, Letenneur L, Helmer C, Dartigues JF, Barberger-Gateau P.
Nutritional factors and risk of incident dementia in the PAQUID longitudinal
cohort.
J Nutr Health Aging. 2004;8(3):150-4.
PMID: 15129300 [PubMed - indexed for MEDLINE]

2: Luchsinger JA, Tang MX, Siddiqui M, Shea S, Mayeux R.
Alcohol intake and risk of dementia.
J Am Geriatr Soc. 2004 Apr;52(4):540-6.
PMID: 15066068 [PubMed - indexed for MEDLINE]

3: Letenneur L, Larrieu S, Barberger-Gateau P.
Alcohol and tobacco consumption as risk factors of dementia: a review of
epidemiological studies.
Biomed Pharmacother. 2004 Mar;58(2):95-9. Review.
PMID: 14992790 [PubMed - indexed for MEDLINE]

4: Truelsen T, Thudium D, Gronbaek M; Copenhagen City Heart Study.
Amount and type of alcohol and risk of dementia: the Copenhagen City Heart
Study.
Neurology. 2002 Nov 12;59(9):1313-9.
PMID: 12427876 [PubMed - indexed for MEDLINE]

5: Schlienger JL.
[Beneficial and deleterious effects of alcoholic beverages]
Rev Prat. 1999 Feb 15;49(4):367-72. Review. French.
PMID: 10319684 [PubMed - indexed for MEDLINE]

6: Leibovici D, Ritchie K, Ledesert B, Touchon J.
The effects of wine and tobacco consumption on cognitive performance in the
elderly: a longitudinal study of relative risk.
Int J Epidemiol. 1999 Feb;28(1):77-81.
PMID: 10195668 [PubMed - indexed for MEDLINE]

7: Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R,
Renaud S, Breteler MB.
Wine consumption and dementia in the elderly: a prospective community study in
the Bordeaux area.
Rev Neurol (Paris). 1997 Apr;153(3):185-92.
PMID: 9296132 [PubMed - indexed for MEDLINE]

8. Galanis DJ, Joseph C, Masaki KH, Petrovitch H, Ross GW, White L.
A longitudinal study of drinking and cognitive performance in elderly Japanese
American men: the Honolulu-Asia Aging Study.
Am J Public Health. 2000 Aug;90( 8 ):1254-9.
PMID: 10937006 [PubMed - indexed for MEDLINE]

9. Leroi I, Sheppard JM, Lyketsos CG.
Cognitive function after 11.5 years of alcohol use: relation to alcohol use.
Am J Epidemiol. 2002 Oct 15;156( 8 ):747-52.
PMID: 12370163 [PubMed - indexed for MEDLINE]

10: Ruitenberg A, van Swieten JC, Witteman JC, Mehta KM, van Duijn CM, Hofman A,
Breteler MM.
Alcohol consumption and risk of dementia: the Rotterdam Study.
Lancet. 2002 Jan 26;359(9303):281-6.
PMID: 11830193 [PubMed - indexed for MEDLINE]

11: Huang W, Qiu C, Winblad B, Fratiglioni L.
Alcohol consumption and incidence of dementia in a community sample aged 75
years and older.
J Clin Epidemiol. 2002 Oct;55(10):959-64.
PMID: 12464371 [PubMed - indexed for MEDLINE]