| Diffusion tensor imaging (DTI) studies have consistently identified white matter changes in individuals with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). However, fewer studies have examined asymptomatic individuals at risk for AD, and findings are inconsistent. In this study, we examined DTI differences across the spectrum of AD risk (genetic and family history) in asymptomatic individuals. Unique to this study is the inclusion of an amnestic MCI comparison group intended to determine how the white matter (WM) microstructure of individuals at risk for AD compares to individuals demonstrating objective memory impairment. Four groups were identified: (1) cognitively intact and no gene risk or family history of AD, (2) cognitively intact and positive for at least one APOE epsilon 4 allele, (3) reported history of AD and no APOE epsilon 4 allele, and (4) met criteria for amnestic MCI. Group differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were examined in several WM tract regions-of-interest. We also included an examination of the relationship between these baseline DTI measures and both current memory performance and memory change over 3 years. The MCI group performed significantly lower on measures of cognition, but there were no differences in cognitive performance between the Low Risk, Family History, and APOE epsilon 4 groups. Significant DTI differences did not emerge between the cognitively asymptomatic groups, with the exception of significantly higher DA in the left uncinate fasciculus in the APOE epsilon 4 group compared to the Low Risk and Family History groups. Conversely, the MCI group differed from the asymptomatic groups on all DTI indices; several distinct patterns of DTI abnormalities were observed consistent with the possibility that the underlying WM neuropathology associated with MCI was not uniform. Furthermore, DTI measures were highly correlated with concurrent memory measures across the entire sample in most of these WM tracts, but not when only asymptomatic subjects were examined. However, DTI measures were significant predictors of prospective change in memory performance over three years in asymptomatic participants. Overall, these findings suggest that DTI is less sensitive to risk factors among asymptomatic individuals with and without genetic risk factors for AD, but does appear to be sensitive to the presence cognitive impairment and a predictor of future memory decline in cognitively asymptomatic older adults. As such, DTI may be a useful biomarker of future cognitive decline in healthy older adults. |
