Memory Impairment Study (Mild Cognitive Impairment Study)

This clinical trial will be a multicenter, randomized, double-blind, placebo- controlled, parallel-group study of vitamin E and donepezil in 720 subjects with mild cognitive impairment (MCI). Subjects will be randomized to one of three treatment groups (240 subjects per treatment group): 1) Placebo vitamin E and placebo donepezil plus a multivitamin daily. 2) Vitamin E (2,000 I) and placebo donepezil plus a multivitamin daily.3) Donepezil (10 mg) and placebo vitamin E plus a multivitamin daily. The study will be conducted over three years, with clinical evaluations every 3 months for the first 6 months and then every 6 months. Subjects randomized to donepezil will start a dose of 5 mg daily. Donepezil will be increased to 10 mg after six weeks. Subjects randomized to vitamin E will start at 1,000 I daily. The dose of Vitamin E will be increased to 2,000 I after six weeks. There will be a 12-month recruitment period. The primary endpoint will be time to development of Probable or Possible AD according to NINCDS-ADRDA criteria. Upon determination of a clinical diagnosis of AD, documentation will be sent to the ADCS Coordinating Center and forwarded to the Central Review Committee for verification. Upon verification, of conversion to diagnosis of AD, subjects will stop taking the donepezil study medication or its corresponding placebo, without breaking the blind, and will be offered open label donepezil at a scheduled visit one month after the prior diagnostic visit. Donepezil will be offered to subjects who convert to AD until the subject completes three years from the baseline visit. Based on an estimated incidence of AD of 15% per year, the study has 85% power to detect a 33% or greater reduction in conversion to AD over 3 years. Secondary outcome measures will include change on the Alzheimer's Disease Assessment Scale (ADAS-COG), the Neuropsychological Battery, the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Scale (CDR), the Global Deterioration Scale (GDS), ADCS- Activities of Daily Living Inventory (ADCS-ADL), a Pharmacoeconomics scale, and a Quality of Life scale. Compliance will be monitored through the measurement of alpha-tocopherol levels and pill counts at each visit.