Intracranial Abnormalities with Diffusion Restriction

Meyers, Steven P.

doi:10.1016/j.mric.2021.02.004

Cited by 4 publications

(2 citation statements)

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“…18 These supportive findings notwithstanding, our interpretations still bear validation in experimental or transgenic models of AD, although this study replicates previously published findings that arrived at similar conclusions (reviewed below). It is also important to note that the magnitude of the diffusion restriction found here is substantially smaller than that observed in acute ischemia and other severe brain pathologies, 49 suggesting different mechanisms that have yet to be further explored. Thus, although all our interpretations are restricted by the technique's unique lens, these inferences are informed by the extant literature on myelin/ glia and innovations in biophysical modeling, offering new perspectives and informed speculations on the nexus of healthy and pathological brain aging.…”

Section: Discussionmentioning

confidence: 62%

Greater Diffusion Restriction in White Matter in Preclinical Alzheimer Disease

Benitez

Jensen

Thorn

et al. 2022

Annals of Neurology

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Objective: The Alzheimer's continuum is biologically defined by beta-amyloid deposition, which at the earliest stages is superimposed upon white matter degeneration in aging. However, the extent to which these co-occurring changes is characterized is relatively underexplored. The goal of this study was to use diffusional kurtosis imaging (DKI) and biophysical modeling to detect and describe amyloid-related white matter changes in preclinical Alzheimer disease. Methods: Cognitively unimpaired participants ages 45 to 85 years completed brain magnetic resonance imaging, amyloid positron emission tomography (florbetapir), neuropsychological testing, and other clinical measures at baseline in a cohort study. We tested whether beta-amyloid-negative (ABÀ) and -positive (AB+) participants differed on DKIbased conventional (ie, fractional anisotropy [FA], mean diffusivity [MD], mean kurtosis) and modeling (ie, axonal water fraction [AWF], extra-axonal radial diffusivity [D e,⊥ ]) metrics, and whether these metrics were associated with other biomarkers. Results: We found significantly greater diffusion restriction (higher FA/AWF, lower MD/D e,⊥ ) in white matter in AB+ than ABÀ (partial η 2 =0.08-0.19), more notably in the extra-axonal space within primarily late myelinating tracts. Diffusion metrics predicted amyloid status incrementally over age (area under the curve = 0.84) with modest yet selective associations, where AWF (a marker of axonal density) correlated with speed/executive functions and neurodegeneration, whereas D e,⊥ (a marker of gliosis/myelin repair) correlated with amyloid deposition and white matter hyperintensity volume. Interpretation: These results support prior evidence of a nonmonotonic change in diffusion behavior, where an early increase in diffusion restriction is hypothesized to reflect inflammation and myelin repair prior to an ensuing decrease in diffusion restriction, indicating glial and neuronal degeneration.

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