Abnormal white matter independent of hippocampal atrophy in amnestic type mild cognitive impairment

Hippocampal atrophy is the key marker in the pathogenesis of Alzheimer's disease (AD), which is associated with white matter (WM) disruption. This type of WM disruption could partly explain AD-related pathology. However, relatively little attention has been directed toward WM disruption which may be independent of these fundamental gray matter (GM) changes in amnestic mild cognitive impairment (aMCI) which is associated with high risk of AD. To evaluate the differences of WM integrity between aMCI patients (N = 32) and healthy controls (N = 31), whole-brain voxel-based methods were applied to diffusion tensor imaging. To explore the possible independence of WM changes from GM loss, an index of hippocampal atrophy was used to partial out GM effects. aMCI patients showed WM disruption in frontal lobe, temporal lobe, internal capsule, cingulate gyrus and precuneus. The findings supported the evidence of independent patterns of degeneration in WM tracts which may co-act in the WM pathological process of aMCI patients. As aMCI is a putatively prodromal syndrome to AD, these data may assist with a better understanding of WM pathological change associated with the development of AD.