In this article, the challenges faced by several noted population studies for Alzheimer dementia in operationalizing current clinical diagnostic criteria for Alzheimer's disease (AD) have been reviewed. Differences in case ascertainment, methodological biases, cultural and educational influences on test performance, inclusion of special populations such as underrepresented minorities and the oldest old, and detection of the earliest symptomatic stages of underlying AD have been considered. Classification of Alzheimer dementia may be improved by the incorporation of biomarkers for AD if the sensitivity, specificity, and predictive value of the biomarkers are established and if they are appropriate for epidemiological studies, as may occur should a plasma biomarker be developed. Biomarkers for AD could also facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in "mixed dementia".