Objective: To determine whether preclinical Alzheimer disease (AD), as detected by the amyloid-imaging agent Pittsburgh Compound B (PiB) in cognitively normal older adults, is associated with risk of symptomatic AD. Design: A longitudinal cohort study of cognitively normal older adults assessed with positron emission tomography (PET) to determine the mean cortical binding potential for PiB and followed up with annual clinical and cognitive assessments for progression to very mild dementia of the Alzheimer type (DAT). Setting: The Alzheimer's Disease Research Center, Washington University, St Louis, Missouri. Participants: One hundred fifty-nine participants with a mean age of 71.5 years with a Clinical Dementia Rating (CDR) of 0 on a PET PiB scan at baseline. Main Outcome Measure: Progression from CDR 0 to CDR 0.5 status (very mild dementia). Results: Twenty-three participants progressed to CDR 0.5 at follow-up assessment (range, 1-5 assessments after PET PiB). Of these, 9 also were diagnosed with DAT. Higher mean cortical binding potential values for PiB (hazard ratio, 4.85; 95% confidence interval, 1.22-19.01; P=.02) and age (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=.03) predicted progression to CDR 0.5 DAT. The CDR 0.5 DAT group showed decline in 3 cognitive domains (episodic memory, semantic memory, and visuospatial performance) and had volume loss in the parahippocampal gyrus (includes entorhinal cortex) compared with individuals who remained at CDR 0. Conclusion: Preclinical AD as detected by PET PiB is not benign, as it is associated with progression to symptomatic AD.