Amyloid-PET of the white matter: Relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease. Issue 6 (June 2023)

• Record Type: Journal Article
• Authors: Ottoy, Julie; Ozzoude, Miracle; Zukotynski, Katherine; Kang, Min Su; Adamo, Sabrina; Scott, Christopher; Ramirez, Joel; Swardfager, Walter; Lam, Benjamin; Bhan, Aparna; Mojiri, Parisa; Kiss, Alex; Strother, Stephen; Bocti, Christian; Borrie, Michael; Chertkow, Howard; Frayne, Richard; Hsiung, Robin; Laforce, Robert Jr; Noseworthy, Michael D; Prato, Frank S; Sahlas, Demetrios J; Smith, Eric E; Kuo, Phillip H; Chad, Jordan A; Pasternak, Ofer; Sossi, Vesna; Thiel, Alexander; Soucy, Jean-Paul; Tardif, Jean-Claude; Black, Sandra E; Goubran, Maged;
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 43:Issue 6(2023)
• Page Start: 921
• Page End: 936
• Publication Date: 2023-06
• Subjects: Alzheimer's disease -- amyloid-PET -- diffusion MRI -- free water -- white matter; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X231152001
• Languages: English
• ISSNs: 0271-678X

Abstract

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.