To identify neuropsychiatric and somatic factors related to survival in early-onset Alzheimer's disease, we longitudinally studied 108 patients (35 male, 73 female) with early-onset Alzheimer's disease who were 46 to 64 years old at onset and 50 to 69 years old when diagnosed at our institution. A five-year follow-up, 30 patients had died. Pneumonia was the most common cause (73%), followed by malignancy (20%) and heart disease (7%). Kaplan-Meier survival curves showed a lower survival rate in patients with early-onset Alzheimer's disease than in age- and sex-matched life-table data in Japan. In Cox proportional hazards analysis, male gender, early disease onset, concurrent physical illness at time of diagnosis, and a low mini-mental state examination score increased the likelihood of death in patients with early-onset Alzheimer's disease. Our study confirmed that these patients have considerable excess mortality and a different pattern of cause of death than in the general population. Gender, age at onset, physical illness, and cognitive function strongly influenced survival. These factors may be predictors of mortality in patients with early-onset Alzheimer's disease that are useful in counseling patients and their families.