Diffusion MRI biomarkers of white matter microstructure vary nonmonotonically with increasing cerebral amyloid deposition

Jian W. Dong, Ileana O. Jelescu, Benjamin Ades-Aron, Dmitry S. Novikov, Kent Friedman, James S. Babb, Ricardo S. Osorio, James E. Galvin, Timothy M. Shepherd, Els Fieremans

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Beta amyloid (Aβ) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Aβ burden: Aβ− [mean mSUVr ≤1.00], Aβi [1.00 < mSUVr <1.17], Aβ+ [mSUVr ≥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. Aβi group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both Aβ− and Aβ+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled Aβ−/Aβi and pooled Aβi/Aβ+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising Aβ burden. In the later stages of Aβ accumulation, neurodegeneration is the predominant factor affecting diffusion.

Original languageEnglish (US)
Pages (from-to)118-128
Number of pages11
JournalNeurobiology of aging
Volume89
DOIs
StatePublished - May 2020

Keywords

  • Alzheimer
  • Amyloid
  • Diffusion MRI
  • Kurtosis
  • White matter
  • White matter tract integrity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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