Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD.
Keywords: AD, Alzheimer's disease; AWF, axonal water fraction; Alzheimer's disease; CP, cerebral peduncle; DKI, diffusional kurtosis imaging; DTI, diffusion tensor imaging; Daxon, intrinsic axonal diffusivity; De,∥, axial extra-axonal diffusivity; De,⊥, radial extra-axonal diffusivity; Diffusion MRI; Diffusional kurtosis imaging; FA, fractional anisotropy; ILF, inferior longitudinal fasciculus; NC, normal control; PLIC, posterior limb of the internal capsule; SLF, superior longitudinal fasciculus; Verbal fluency; WM, white matter; WMTI, white matter tract integrity; White matter; aMCI, amnestic mild cognitive impairment.