OBJECTIVES To test the prediction of survival using magnetic resonance imaging (MRI)-derived global and regional brain volumes in subjects aged 78 to 79 without dementia. DESIGN Observational follow-up study. SETTING University teaching hospital. PARTICIPANTS Participants born in 1921, recruited in 1997/98 to a longitudinal study, who underwent brain MRI in 1999/2000. MEASUREMENTS Vital status on May 12, 2006, global and regional brain volumes. RESULTS Thirty-seven of 98 (34.9%) participants died during follow-up. After adjustment for cognitive ability at time of MRI examination, childhood intelligence, sex, hypertension, smoking history, obesity, hyperlipidemia, and age at MRI, proportion of intracranial volume occupied by the brain (brain fraction) predicted death before age 85 (P=.04). Participants with brain fraction less than 0.726 had more than twice the relative risk (2.8, 95% confidence interval=1.1-7.3) of death than participants with brain fraction greater 0.726. Lower survival was significantly associated with lower gray matter volumes in bilateral parietal and left frontoparietal areas and with lower white matter volumes in left parietal and right posterior temporal regions. Cox regression analysis showed that parietal white matter volume (P=.003), a subsequent diagnosis of dementia (P <.001), and sex (P=.004) were independent predictors of survival. CONCLUSION In participants aged 78 to 79, a lower global brain fraction predicted survival to approximately age 85. Smaller regional volumetric brain reductions, seen in Alzheimer's disease (AD), also predicted survival independent of dementia. The presence of prodromal AD probably explain the main findings.