Widespread white matter degeneration preceding the onset of dementia

Abstract

Background—Brain atrophy in subjects with mild cognitive impairment (MCI) introduces partial volume effects, limiting the sensitivity of diffusion tensor imaging to white matter microstructural degeneration. Appropriate correction isolates microstructural effects in MCI that might be precursors of Alzheimer’s disease (AD). Methods—Forty-eight participants (18 MCI, 15 AD and 15 healthy controls) had MRI scans and clinical evaluations at baseline and follow-up after 36 month. 10 MCI subjects were diagnosed with AD at follow-up and 8 remained MCI. Free-water corrected measures on the white matter skeleton were compared between groups. Results—Free-water-corrected radial diffusivity, but not un-corrected radial diffusivity, was increased across the brain of the converted group compared to the non-converted group (P<0.05). The extent of increases was similar to that found comparing AD with controls. Conclusion—Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD.