Gray Matter Volumetric Differences in Healthy Older Adults at Risk for Alzheimer's Disease Nathaniel Gallegos, University of Arizona, Graduate Student It is well-documented that gray matter volume decreases in Alzheimer's disease (AD). Gray matter volumes have been shown to be correlated with disease progression and cognitive deficits. These brain changes can be detected in some of the earlies stages of this disease, such as the preclinical stages where there are no cognitive symptoms of AD. In this study, we investigated gray matter volume loss in individuals who are at high risk of developing AD based on several risk factors, including carrying the apolipoprotein e4 allele (APOE-4) or having a first-degree family history of AD. We analyzed the gray matter volumes in 46 cognitively healthy older adults, ages 49 to 89 with an average of 70 years, with one or both risk factors, and an additional 32 matched controls without either risk factor. Voxel-based morphometry of high-resolution MRI showed significantly smaller gray matter volumes in risk groups compared to controls in a region of the left anterior hippocampus, as well as other brain regions including the left temporal pole and the right superior frontal gyrus. Those in the risk group also scored significantly lower on Trails B and the California Verbal Learning Test compared to those in the no-risk group. This study provides evidence that these risk factors have an influence on gray matter volumes and show a detectable effect on cognition even in cognitively healthy individuals. Subsequent analyses will determine which of the risk factors are driving these differences.