Identifying persons with mild cognitive complaints who are at risk for Alzheimer's disease (AD) will enable the start of antidementia treatments before extensive brain damage develops. Recent research developments link the apolipoprotein E-4 (APOE-4) allele to late-onset familial and late-onset sporadic AD. Studies of relatives at risk for familial AD using brain imaging (positron emission tomography [PET]) and genetic assessments suggest that relatives with the APOE-4 allele have lower parietal metabolism than those without this allele. Approaches that might increase sensitivity and specificity include, among others, pharmacologic challenges of short-acting anticholinergic agents and memory activation during functional scanning. Such strategies should eventually assist in early detection of AD and in vivo therapeutic monitoring of brain function during experimental antidementia treatment trials.