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Heavy Drinking, Smoking Linked to
Earlier Onset of Alzheimer’s Disease
CHICAGO—
Heavy drinking and smoking are risk factors for earlier development of late-onset Alzheimer’s disease, according to Ranjan Duara, MD. The APOE ε4 genotype, a known risk factor for Alzheimer’s disease, is additive to smoking and drinking, but these risk factors are not synergistic, he reported at the 60th Annual Meeting of the American Academy of Neurology.
“These findings emphasize the importance of public health messages aimed at limiting drinking and avoiding cigarette smoking, especially in persons with the APOE ε4 genotype and a family history of Alzheimer’s disease,” said Dr. Duara. “By changing these behaviors, the age of onset of Alzheimer’s disease can be extended. It is also important not to de-emphasize exercise, healthy diet, and social connections, which are thought to delay onset of Alzheimer’s disease.” Dr. Duara is Medical Director of the Wien Center for Alzheimer’s Disease and Memory Disorders at Mount Sinai Medical Center in Miami Beach.
RISK FACTORS AND AGE OF ALZHEIMER'S DISEASE ONSET
A total of 938 people 60 or older who were diagnosed with probable or possible Alzheimer’s disease were included in the study, which was designed to assess the impact of alcohol use, smoking, and APOE allele on late-onset Alzheimer’s disease. The prevalence of Alzheimer’s disease increases with age and roughly doubles every five years from age 65 on, noted Dr. Duara. “We wanted to look at these risk factors, because if the onset of Alzheimer’s disease could be delayed by about five years, the estimated overall prevalence could be reduced by almost 50%,” he said. “Factors that are modifiable could have a dramatic impact on the number of cases of Alzheimer’s disease.”
The APOE genotype lies on chromosome 19 and has several alleles—each allele can be associated with increased or decreased risk for a particular disease. In the case of Alzheimer’s disease, ε4 is associated with earlier age of disease onset, while ε2 is associated with a lower risk of the disease. Frequently, individuals can carry gene pairs with different alleles. For example, an individual might carry the combination of the APOE ε3 and ε4 alleles (expressed as ε34). One copy of ε4 confers a two to five times increased risk of Alzheimer’s disease, whereas two copies of this genotype (eg, ε44) are associated with a fivefold to 10-fold increase, explained Dr. Duara.
Alcohol consumption has a multidimensional impact on Alzheimer’s disease. Moderate consumption of alcohol appears to be protective, but some studies have suggested that heavy drinking increases the risk of Alzheimer’s disease. Initially, smoking was thought to be protective; however, most researchers now agree that it is a risk factor for the disease, Dr. Duara said.
ALCOHOL, SMOKING, AND APOE ε4
Complete data on 686 of the 938 patients was available. Informants (spouses or other family members or caregivers) were asked about age of disease onset, as well as smoking and alcohol consumption. Participants were given blood tests for APOE genotype. Mean age of onset was about 75. Mean Mini-Mental State Examination score was 18 (reflecting the upper level of moderate dementia). Sixty-four percent of the patients were female; 58% were white non-Hispanic, 38% were white Hispanic, and 4% were African American.
Twenty-seven percent of subjects were ε4-positive. Fifty-four percent had never smoked, 19% smoked less than one pack of cigarettes per day, 14% smoked one pack per day, and 13% smoked more than one pack per day. Thirty-two percent were mild drinkers (less than one drink per day), 11% were moderate drinkers (one to two drinks per day), and 7% were heavy drinkers (more than two drinks per day).
If no risk factors were present, mean age of onset was 77.2. The mean age of Alzheimer’s disease onset for those with the APOE ε23, ε33, ε34, and ε44 genotypes was 77.6, 76.6, 74.0, and 71.3 years, respectively. Among all heavy smokers the mean age of onset was 73.2 years, and among all heavy drinkers it was 71.5 years.
When risk factors were combined, age of onset was earlier. Those who were ε4-positive and smokers had a significantly younger age of onset, as did those who were ε4-positive and drinkers. Each of these combinations reduced the age of onset by an average of three years. Patients with all three risk factors had a mean age of onset of 68.5, which was highly significant, Dr. Duara said.
This was a retrospective study based on informants’ reports on age of onset and risk factors, so there is potential for selective recall bias, Dr. Duara commented. He added that the effect of combined risk factors on age of Alzheimer’s disease onset needs replication in a large, randomized, population-based study. “Thirty percent to 40% of our subjects were Hispanics, originally from Cuba, and they may have had additional risk factors that affected results,” he said.
APOE SCREENING NOT A RECOMMENDED MEASURE FOR ALZHEIMER'S DISEASE
Dr. Duara concluded that APOE screening “is not a useful measure for risk of developing Alzheimer’s disease, and the use of APOE as a screening measure for Alzheimer’s disease among older persons has not been recommended. But as we learn more about the interaction of APOE genotype and other risk factors and about how changes in lifestyle and diet and the rigor with which we control cardiovascular disease may reduce risk, these current recommendations may change. If people have a better understanding of their risk for developing Alzheimer’s disease, they may be more vigilant about making changes in their lifestyle to reduce their risk.”
—Alice Goodman
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