Amyloid-PET of the white matter: Relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease

  • Julie Ottoy (Creator)
  • Miracle Ozzoude (Creator)
  • Katherine Zukotynski (Creator)
  • Min Su Kang (Creator)
  • Sabrina Adamo (Creator)
  • Christopher Scott (Creator)
  • Joel Ramirez (Creator)
  • Walter Swardfager (Creator)
  • Benjamin Lam (Creator)
  • Aparna Bhan (Creator)
  • Parisa Mojiri (Creator)
  • Alex Kiss (Creator)
  • Stephen Strother (Creator)
  • Christian Bocti (Creator)
  • Michael Borrie (Creator)
  • Howard Chertkow (Creator)
  • Richard Frayne (Creator)
  • Ging Yuek Robin Hsiung (Creator)
  • Robert Laforce (Creator)
  • Michael D. Noseworthy (Creator)
  • F. S. Prato (Creator)
  • D. Sahlas (Creator)
  • Eric E. Smith (Creator)
  • Phillip H Kuo (Creator)
  • Jordan A. Chad (Creator)
  • Ofer Pasternak (Creator)
  • Vesna Sossi (Creator)
  • Alexander Thiel (Creator)
  • Jean Paul Soucy (Creator)
  • Jean Claude Tardif (Creator)
  • Sandra Black (Creator)
  • Maged Goubran (Creator)
  • Min Su Kang (Creator)
  • Benjamin Lam (Creator)
  • Robin Hsiung (Creator)
  • Jean Paul Soucy (Creator)
  • Jean Claude Tardif (Creator)
  • Sandra E Black (Creator)



White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (Aβ-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered Aβ-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to Aβ-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in Aβ-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in Aβ-PET related more closely to higher cortical Aβ (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and Aβ-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.
Date made available2023
PublisherSAGE Journals

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