Heavy Drinking, Smoking Lead to Earlier Onset of Alzheimer's Disease

Caroline Cassels

April 22, 2008

April 22, 2008 (Chicago, Illinois) — New research suggests that heavy drinking and smoking significantly lower the age of onset for Alzheimer's disease (AD), with an individual effect that is roughly equivalent to the APOE ε4 allele alone. The research was presented here at the American Academy of Neurology 60th Annual Meeting.

Investigators at the Mount Sinai Medical Center in Miami Beach, Florida found that heavy smokers developed AD 2.3 years sooner than nonsmokers and that heavy drinkers developed the disease 4.8 years earlier than those who were not heavy drinkers. Individuals with the APOE ε4 variant developed AD 3 years earlier than those without the variant.

However, study subjects with all 3 risk factors developed the disease an average of 8.5 years earlier than their counterparts who had none of these risks.

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"While it is already known from many previous studies that these 3 risk factors affect Alzheimer's risk, this is the first time that they have been looked at in combination, and it is the first time they have been looked at in terms of how they affect disease onset," principal investigator Ranjan Duara, MD, told Medscape Neurology & Neurosurgery

According to Dr. Duara, the researchers wanted to look at modifiable risk factors that could potentially influence the age of onset of AD. He noted that recent longitudinal studies have shown that smoking increases the risk for AD and dementia by approximately 50%.

Dramatic Impact

While moderate alcohol consumption has been shown to protect against AD, Dr. Duara pointed out that heavy drinking has been shown to increase AD risk.

"We know the prevalence of Alzheimer's increases with age and roughly doubles every 5 years starting at about age 65. If disease onset could be delayed by about 5 years, it is estimated that the overall prevalence of Alzheimer's could be reduced by almost 50%. So modifiable factors that could delay disease could have a dramatic effect," he said.

The clinic-based study included 938 patients age 60 years or older who had possible or probable AD according to National Institute of Neurological Communication Disorders and Stroke–Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

During an initial intake interview, reliable informants were used to determine patients' age of disease onset as well as smoking and drinking history. In addition, all study subjects were screened for the APOE ε4 variant.

Heavy drinkers were those defined as those who drank more than 2 alcoholic drinks per day, moderate drinkers 1 to 2 drinks per day, and mild drinkers less than 1 drink per day.

Similarly, heavy smokers were defined as those who smoked 2 or more packs of cigarettes per day, moderate smokers 1 to 2 packs daily, and mild smokers less than 1 pack per day.

Cumulative Effect

The final analysis included 686 patients who had a full complement of study data. The mean age of onset was about 75 years. The average score on the Mini-Mental State Examination (MMSE) was about 18, putting the study cohort at the upper level of moderate dementia.

Of the study population, 27% was positive for the APOE ε4 variant. In terms of smoking, 54% of individuals never smoked, 19% smoked less than 1 pack per day, and 13% smoked more than 1 pack of cigarettes per day.

About 50% of the study participants were nondrinkers; 32%, 11%, and 7% were mild, moderate, and heavy drinkers, respectively.

"We found that, individually, each of these risk factors lowered age of onset of disease by about 2 to 3 years. However, when these risk factors occurred together, there was a cumulative effect, such that if they had any 2 [risk factors], they developed the disease 5 to 6 years earlier, and if they had all 3, the disease onset was 8 to 9 years earlier," said Dr. Duara.

While the study results were "highly significant," Dr. Duara said further research is required to confirm the findings in a randomized, population-based study.

Nevertheless, he said, the public health implications are clear. While heavy alcohol use and smoking are already known risk factors for a number of diseases, particularly heart disease, Dr. Duara said the associated risk for Alzheimer's disease has not been emphasized strongly enough.

"Alzheimer's is a major burden in this country, not only for the patients but for their caregivers. Anything we can do to delay the age of onset will have a very important public health benefit. I think doctors, and general practitioners in particular, should be emphasizing Alzheimer's-disease prevention as an additional reason for moderation in drinking and avoiding smoking," he said.

The study was supported by the State of Florida Department of Elder Affairs.

American Academy of Neurology 60th Annual Meeting: Abstract P04.071. Presented April 16, 2008.

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