Donepezil and Brain Activity Patterns in Those at Risk For Alzheimer's Disease

HYPOTHESIS 1. Cognitively intact individuals with normal brain morphology at genetic risk for developing Alzheimer's' Disease (AD) show alterations in brain activation patterns during tasks that require memory compared to similar individuals with lower risk for developing AD. 2. Donepezil, a cholinesterase inhibitor, can normalize such brain activation patterns in subjects at risk for AD. SPECIFIC AIMS 1. To replicate a recent study1, and compare brain activation in subjects genetically at risk for AD (carriers of the є4 allele of the apolipoprotein E gene (APOE)) with subjects at lower risk for AD (lacking the є4 allele) during tasks that require memory, via functional magnetic resonance imaging (fMRI). 2. To determine if administration of a drug currently indicated in the treatment of AD, donepezil, can reverse fMRI brain activation patterns of at risk subjects to patterns similar to those of subjects at lower genetic risk for AD.