Increased fMRI signal with age in familial Alzheimer's disease mutation carriers.

Although many Alzheimer's disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of nondemented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 nondemented autosomal dominant AD mutation carriers with fMRI activity in eight of their noncarrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images. Because age of disease onset is relatively consistent within families, we also correlated fMRI activity with subjects' distance from the median age of diagnosis for their family. Mutation carriers did not show significantly different voxelwise fMRI activity from noncarriers as a group. However, as they approached their family age of disease diagnosis, only mutation carriers showed increased fMRI activity in the fusiform and middle temporal gyri. This suggests that during novelty encoding, increased fMRI activity in the temporal lobe may relate to incipient AD processes.