Alcohol and Dementias -- What To Advise?

Summarized by Robert W. Griffith, MD
March 7, 2002

Introduction

Once again the Rotterdam Study has produced findings suggesting a significant protective effect of a familiar factor on the risk of dementia. This time, it's alcohol consumption. Light to moderate alcohol intake is known to reduce the risk of coronary heart disease, ischemic stroke, and total mortality. It's also accepted that vascular disease is associated with cognitive impairment and dementia, so that it seemed reasonable to the Rotterdam investigators to assess the possible association between alcohol intake and the frequency of dementia. An earlier study has shown a significant inverse association between the amount of wine consumed and the risk of dementia. ¹

Method

All persons 55 or older living in a suburb of the Dutch city in 1990-1993 were invited to participate in the Rotterdam Study. Almost 8,000 (78%) accepted, and over 7,000 of these participants who were free of dementia at baseline (and therefore at risk of developing it) were enrolled. Food-frequency questionnaires were administered at the second visit during the enrollment phase, and 5,395 of those returned were deemed adequate for analysis.

Participants were asked if they ever drank alcohol. If they said 'yes', they were asked about the frequency. Those that drank alcohol at least twice a month were asked to give details on the average amounts of specific drinks taken (wine, beer, liquor, or fortified wine). Changes in pattern of alcohol use were explored, as well as possible binge drinking (>6 drinks on one day). Categories for alcohol frequency were built: none, </=1 drink per week, >/=1 per week but </=1 day, 1-3 drinks per day, and >/=4 per day.

General practitioners reported all cases of suspected dementia during the study period, up to December 1999, and screening was also done at follow-up examinations. Dementia screening followed a 3-step protocol: first, a short test of cognition (MMSE & GMS ²), then full cognitive testing, including an interview of an informant; finally, suspected dementia cases were examined by a neurologist and had neuropsychological tests, and, in some cases, magnetic resonance imaging (MRI) of the brain. In those with dementia, a distinction was made between Alzheimer disease and vascular dementia.

Data were collected on possible confounding variables: age, sex, diabetes, systolic blood pressure, education, smoking, body mass index (BMI), history of stroke or myocardial infarction, and apolipoprotein E (APOE) genotype.

Evaluations were directed at determining the risk of dementia associated with alcohol consumption, using Cox's proportional hazards regression analysis. Hazards ratios were calculated after adjusting for the above variables.

Results

The average follow-up period was 6 years. During that time, 197 participants developed dementia. Alzheimer disease was diagnosed in 146 (74%), vascular dementia in 29 (15%), and other types (e.g. Parkinson's) in 22 (11%).

Median alcohol consumption was about 1 drink every 3½ days. Men drank more than women, consuming chiefly beer and liquor; women drank more fortified wine.

As shown in the table below, taking 1-3 drinks a day was found to be significantly associated with a reduced risk of all dementias and of vascular dementias.

Adjusted Hazard Ratios (95% CI) for dementias, using 'no alcohol' = 1.0

	</=1 drink/week	>/=1/wk, but </=1/day	1-3 drinks/day	>/=4 drinks/day
All dementias	0.82 (0.56-1.22)	0.75 (0.51-1.11)	0.58 (0.38-0.90)	1.0 (0.39-2.59)
Alzheimer's	0.91 (0.58-1.44)	0.91 (0.58-1.44)	0.72 (0.43-1.20)	1.17 (0.35-3.55)
Vascular	0.79 (0.30-2.08)	0.36 (0.12-1.08)	0.30 (0.10-0.92)	1.53 (0.31-7.56)
Other types	0.39 (0.10-1.46)	0.49 (0.17-1.46)	0.37 (0.11-1.18)	Insufficient nos.

These effects were more prominent in men; the age-adjusted all-dementias hazard ratios for 1-3 drinks/day were 0.39 for men, and 0.80 for women, respectively.

Further analyses failed to show an effect of the type of alcohol consumed or of the APOE genotype. The hazards ratios for 1-3 drinks/day estimated after exclusion of subjects who changed their drinking pattern during the study period and exclusion of binge drinkers were 0.57 and 0.56, respectively.

Comments

The authors of the study suggest two possible explanations for their findings. First, alcohol might act through reduction of cardiovascular risk factors, either by inhibiting platelet aggregation or improving the serum lipid profile. The finding that vascular dementias were preferentially influenced is in accord with this mechanism.

Second, alcohol might have a direct action on cognitive function by releasing acetylcholine in the hippocampus. In lab animals, low alcohol concentrations stimulate, while high concentrations inhibit acetylcholine release.

Although these results suggest strongly that light-to-moderate alcohol drinking has a beneficial effect on the development of dementias (especially vascular dementia), they should not be used to advise non-drinkers to take it up, or for rare drinkers to increase their consumption. However, the findings should remove any guilt light-to-moderate drinkers may feel as they enjoy their daily glass (or two). And, they should be used to emphasize that any possible benefits are clearly lost if the drinker exceeds, on average, 4-a-day.

Source

• Alcohol consumption and risk of dementia: the Rotterdam Study. A. Ruitenberg, JC. van Sweiten, JCM. Witteman,  et al., Lancet, 2002, vol. 359, pp. 281--286

Footnotes
1. Orgogozo JM, Dartigues JF, Lafont S, et al. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux are. Rev Neurol (Paris) 1997;153:185-192
2. MMSE = Mini Mental-State Examination, GMS = Geriatric Mental State

Related Links
The PAQUID Study
NSAIDs and Alzheimer Disease -- What to Advise?
Two Treatable Risk Factors for Alzheimer's Disease

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