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

Posted on 2023-02-01 - 05:09

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.

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Journal of Cerebral Blood Flow & Metabolism

AUTHORS (32)

Julie Ottoy
Miracle Ozzoude
Katherine Zukotynski
Min Su Kang
Sabrina Adamo
Christopher Scott
Joel Ramirez
Walter Swardfager
Benjamin Lam
Aparna Bhan
Parisa Mojiri
Alex Kiss
Stephen Strother
Christian Bocti
Michael Borrie
Howard Chertkow
Richard Frayne
Robin Hsiung
Robert Jr Laforce
Michael D Noseworthy
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