To determine if superior health at old age protects against cognitive impairment (CI) and Alzheimer's disease (AD), we prospectively studied 100 optimally healthy oldest-old (85 years) individuals. Initially, subjects represented the top 3% of the oldest old for health. During 5.6 ± 0.3 years of follow-up, 34 subjects developed CI, and 23 progressed to AD. By age 100, probability of CI and AD were .65 ± .09 and .49 ± .10. Median onset age was 97 years for CI and 100 for AD. Clearly, superior health at old age does not guarantee protection against cognitive decline. Lifetime risks were similar to the general population but onset ages were later, suggesting factors that delay onset are key to improving cognitive health in the elderly. In this population, absence of apolipoprotein E-ε4 and male gender were associated with delayed onset, whereas estrogen use and education had no detectable effect on cognitive outcome.