The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer's disease

Objective: This study examined the association between a history of heavy alcohol use and smoking, presence of the apolipoprotein-E epsilon 4 allele (APOE ε4), and age of disease onset in a community dwelling sample of 685 Alzheimer's disease (AD) patients spanning three ethnic groups. Design: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic. Subjects: A clinic-based cohort of white non-Hispanic (WNH; n=397), white Hispanic (WH; n=264), and African-American (AA; n=24) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria. Measurements: The age of onset of AD was obtained from a knowledgeable family member. All patients were assessed for APOE genotype. History of alcohol and tobacco consumption prior to the onset of dementia was obtained via an interview with the patient and the primary caregiver. A history of heavy drinking was defined as >2 drinks per day and a history of heavy smoking was defined as ≥1 pack per day. Results: Presence of an APOE ε4 allele, a history of heavy drinking, or a history of heavy smoking were each associated with an earlier onset of AD by 2-3 years. Patients with all three risk factors were likely to be diagnosed with AD nearly 10 years earlier than those with none of the risk factors. Conclusion: The results suggest that APOE ε4 and heavy drinking and heavy smoking lower the age of onset for AD in an additive fashion. Copyright