{"doi":"10.1177/0271678x231152001","title":"Amyloid-PET of the white matter: Relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease","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.","journal":"Journal of Cerebral Blood Flow & Metabolism","year":2023,"id":340600,"datarank":0.5782225986754658,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.16233429033949853,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.16233429033949853,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":14,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02330510"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":815534,"name":"Miracle Ozzoude","orcid":"0000-0003-4154-2765","position":1,"is_corresponding":false},{"id":514914,"name":"Katherine Zukotynski","orcid":"0000-0003-0584-4387","position":2,"is_corresponding":false},{"id":272072,"name":"Min Su Kang","orcid":"0000-0003-0745-6222","position":3,"is_corresponding":false},{"id":815535,"name":"Sabrina Adamo","orcid":"0000-0002-6105-9984","position":4,"is_corresponding":false},{"id":555738,"name":"Christopher J.M. Scott","orcid":"0000-0002-3236-7523","position":5,"is_corresponding":false},{"id":492200,"name":"Joel Ramirez","orcid":"0000-0002-5582-1776","position":6,"is_corresponding":false},{"id":431867,"name":"Walter Swardfager","orcid":"0000-0002-0030-8908","position":7,"is_corresponding":false},{"id":815537,"name":"Benjamin Lam","orcid":"0000-0001-8010-4915","position":8,"is_corresponding":false},{"id":66854,"name":"Aparna Bhan","orcid":null,"position":9,"is_corresponding":false},{"id":815953,"name":"Parisa Mojiri","orcid":null,"position":10,"is_corresponding":false},{"id":332727,"name":"Alex Kiss","orcid":null,"position":11,"is_corresponding":false},{"id":402085,"name":"Stephen C. 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