Diffusion Tensor Changes According to Age at Onset and Apolipoprotein E Genotype in Alzheimer Disease

Age at onset is one of the most important factors that affects the clinical course in Alzheimer disease (AD), whereas other factors such as apolipoprotein E (apoE) genotype may also play a major role. In this study, we aimed to investigate the effect of age at onset and apoE genotype on white-matter changes in AD using diffusion tensor imaging. About 213 patients with AD and 66 normal individuals underwent diffusion tensor imaging, and apoE genotype was obtained in all AD patients and in 24 normal individuals. When multiple regression analysis was conducted, a younger age at onset was associated with lower fractional anisotropy in both deep-located long-range limbic and association fibers and superficial-located short-range association fibers in the frontal, the temporal, and the parietal lobes, and with a higher mean diffusivity in deep-located fibers and the bilateral medial thalamus. When analyzed separately in apoE e4 carriers and noncarriers, e4 carriers showed an association between a younger age at onset and lower fractional anisotropy, mainly in deep-located fibers, whereas noncarriers showed this association in both deep-located and superficial-located fibers. There was no difference in the spatial distribution between carriers and noncarriers in the association between the age at onset and mean diffusivity. Our results suggest that the topographical distribution of white-matter changes in AD is significantly affected by the interaction between age at onset and apoE genotype.