Designing clinical trials for early (pre-dementia) Alzheimer's disease: determining the appropriate population for treatment.

Treatments that are designed to reduce Alzheimer's disease (AD) pathology may be most useful when given to subjects prior to a diagnosis of AD using current diagnostic criteria. These earlier patients may have early cognitive losses consistent with mild cognitive impairment (MCI) or may be completely asymptomatic. Screening and treatment programs for other disease states have been explored previously; these include cholesterol screening for cardiovascular disease, genetic screening for Huntington ' s disease and screening for some types of cancer. Cancer screening and treatment programs have been developed for colon cancer, breast cancer and prostate cancer. Screening programs for these other disease states are briefly reviewed and are compared to preliminary modeling data describing a hypothetical screening and treatment program for AD. While primary prevention based on screening of asymptomatic individuals using biomarkers has broad appeal, secondary prevention employing treatment of patients with MCI may be more easily implemented.