The longer life expectancy now experienced by persons with Down syndrome (DS) makes it necessary to know the factors influencing survival in older persons with this syndrome. In a prospective longitudinal cohort study of dementia and mortality, 506 persons with DS aged 45 and older were followed for a mean of 4.5 years (range 0.0-7.6 years). Cognitive and social functioning were tested at baseline and annual follow-up. The diagnosis of dementia was determined according to a standardized protocol. Cox proportional hazards modeling was used for survival analysis. Relative preservation of cognitive and functional ability is associated with better survival in this study population. Clinically, the most important disorders in persons with DS that are related to mortality are dementia, mobility restrictions, visual impairment, and epilepsy but not cardiovascular diseases. Also, level of intellectual disability and institutionalization are associated with mortality.