We investigated the risk of cognitive deterioration in relation to alcohol consumption and smoking according to the apolipoprotein E (ApoE) polymorphism. The ApoE epsilon4 allele is an established risk factor for dementia and cognitive impairment. There are also some recent indications that vascular risk factors, including alcohol and tobacco consumption, might play a role in cognition. Our data are from the Epidemiology of Vascular Aging (EVA) study, a prospective study of 1,389 subjects ages 59-71 years at study entry, living the city of Nantes, France, and followed at 4 years after entry. Information on subjects' alcohol and tobacco consumption was collected from a structured questionnaire on food habits. Cognitive performance was assessed by the Mini-Mental State Examination (MMSE). Cognitive deterioration was defined as a decrease of 3 points or more in the Mini-Mental State Examination between study entry and 4-year follow-up. Drinking was associated with a decreased risk of cognitive deterioration in non-ApoE epsilon4 carriers, whereas an opposite association was observed in ApoE epsilon4 carriers. The risk of cognitive deterioration associated with tobacco consumption was also modified according to ApoE genotype, with smokers being at decreased risk of cognitive deterioration among ApoE epsilon4 allele carriers and at increased risk in noncarriers. The effects of alcohol consumption and smoking on the risk of cognitive deterioration appears to be strongly modified by the presence of ApoE epsilon4 allele.