We examined apolipoprotein E (Apo E) polymorphism and methylenetetrahydrofolate reductase (MTHFR) 677 C to T mutation by using the polymerase chain reaction (PCR) method in 100 elderly Japanese aged 60 or more, and assessed whether these genetic factors are associated with an increased risk for the clinical phenotypes of senile dementia, Alzheimer's disease (AD) and vascular dementia (VD) by cross-sectional survey. It was found that the Apo E epsilon 4 allele were associated with an increased prevalence of AD as previously reported. Although, it was not strongly related to the severity of senile dementia, a weak association between the ApoE genotype and the severity of dementia was suggested. The proportion of patients with senile dementia was higher in the group of carriers of MTHFR mutation than in the group of noncarriers. Furthermore, the proportion of male patients with senile dementia was higher in the group of homozygous for the mutation (+/+) than the group without the mutation (-/-). Notably in VD patients, 5 of 7 males had the +/+ genotype. The results suggest that the ApoE epsilon 4 genotype and the MTHFR mutation are associated with the clinical phenotype and the clinical onset of senile dementia.