{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:18:54Z","timestamp":1791807534302,"version":"4.3.4"},"reference-count":61,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:p>White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (A\u03b2-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered A\u03b2-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 A\u03b2-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 A\u03b2-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in A\u03b2-PET related more closely to higher cortical A\u03b2 (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 A\u03b2-PET\u00a0as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.<\/jats:p>","DOI":"10.1177\/0271678x231152001","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:29:16Z","timestamp":1674617356000},"page":"921-936","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Amyloid-PET of the white matter: Relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease"],"prefix":"10.1177","volume":"43","author":[{"given":"Julie","family":"Ottoy","sequence":"first","affiliation":[{"name":"LC Campbell Cognitive Neurology Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-6222","authenticated-orcid":false,"given":"Min Su","family":"Kang","sequence":"additional","affiliation":[{"name":"LC Campbell Cognitive Neurology Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada"},{"name":"Montreal Neurological Institute, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Adamo","sequence":"additional","affiliation":[{"name":"LC Campbell Cognitive Neurology Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Scott","sequence":"additional","affiliation":[{"name":"LC Campbell Cognitive Neurology Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, 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University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Frayne","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Clinical Neuroscience, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Hsiung","sequence":"additional","affiliation":[{"name":"Physics and Astronomy Department and DM Center for Brain Health, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Jr","family":"Laforce","sequence":"additional","affiliation":[{"name":"Clinique Interdisciplinaire de M\u00e9moire, D\u00e9partement des Sciences Neurologiques, Universit\u00e9 Laval, Qu\u00e9bec, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-159X","authenticated-orcid":false,"given":"Michael 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