{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:50:32Z","timestamp":1791622232218,"version":"4.3.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2016-00906"],"award-info":[{"award-number":["2016-00906"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004063","name":"Knut and Alice Wallenberg foundation","doi-asserted-by":"crossref","award":["2017-0383"],"award-info":[{"award-number":["2017-0383"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011898","name":"Marianne and Marcus Wallenberg foundation","doi-asserted-by":"crossref","award":["2015-0125"],"award-info":[{"award-number":["2015-0125"]}],"id":[{"id":"10.13039\/501100011898","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Strategic Research Area MultiPark"},{"name":"Swedish Alzheimer Foundation","award":["AF-939932"],"award-info":[{"award-number":["AF-939932"]}]},{"DOI":"10.13039\/501100003792","name":"Swedish Brain Foundation","doi-asserted-by":"crossref","award":["FO2021-0293"],"award-info":[{"award-number":["FO2021-0293"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, the Sk\u00e5ne University Hospital Foundation","award":["2020-O000028"],"award-info":[{"award-number":["2020-O000028"]}]},{"name":"Regionalt Forskningsst\u00f6d","award":["2020-0314"],"award-info":[{"award-number":["2020-0314"]}]},{"name":"Swedish Federal Government","award":["2018-Projekt0279"],"award-info":[{"award-number":["2018-Projekt0279"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Markers of downstream events are a key component of clinical trials of disease-modifying therapies for Alzheimer\u2019s disease. Morphological metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect amyloid-beta (A\u03b2)- related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion MRI can provide sensitive markers of cortical microstructural changes and to test their associations with multiple aspects of the Alzheimer\u2019s disease pathological cascade, including both A\u03b2 and tau accumulation, astrocytic activation and cognitive deficits.<\/jats:p>\n                  <jats:p>We applied the mean apparent diffusion propagator model to diffusion MRI data from 492 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER-2 cohort. Participants were stratified in A\u03b2-negative\/tau-negative, A\u03b2-positive\/tau-negative and A\u03b2-positive\/tau-positive based on A\u03b2- and tau-PET uptake. Cortical regional values of diffusion MRI metrics and cortical thickness were compared across groups. Associations between regional values of diffusion MRI metrics and both A\u03b2- and tau-PET uptake were also investigated along with the association with plasma level of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation (available in 292 participants).<\/jats:p>\n                  <jats:p>Mean squared displacement revealed widespread microstructural differences already between A\u03b2-negative\/tau-negative and A\u03b2-positive\/tau-negative participants with a spatial distribution that closely resembled the pattern of A\u03b2 accumulation. In contrast, differences in cortical thickness were clearly more limited. Mean squared displacement was also correlated with both A\u03b2- and tau-PET uptake even independently from one another and from cortical thickness. Further, the same metric exhibited significantly stronger correlations with PET uptake than cortical thickness (P &amp;lt; 0.05). Mean squared displacement was also positively correlated with GFAP with a pattern that resembles A\u03b2 accumulation, and GFAP partially mediated the association between A\u03b2 accumulation and mean squared displacement. Further, impairments in executive functions were significantly more associated with mean squared displacement values extracted from a meta-region of interest encompassing regions accumulating A\u03b2 early in the disease process, than with cortical thickness (P &amp;lt; 0.05). Similarly, impairments in memory functions were significantly more associated with mean squared displacement values extracted from a temporal meta-region of interest than with cortical thickness (P &amp;lt; 0.05).<\/jats:p>\n                  <jats:p>Metrics of cortical microstructural alteration derived from diffusion MRI are highly sensitive to multiple aspects of the Alzheimer\u2019s disease pathological cascade. Of particular interest is the link with both A\u03b2-PET and GFAP, suggesting diffusion MRI might reflects microstructural changes related to the astrocytic response to A\u03b2 aggregation. Therefore, metrics of cortical diffusion might be important outcome measures in anti-A\u03b2 treatments clinical trials for detecting drug-induced changes in cortical microstructure.<\/jats:p>","DOI":"10.1093\/brain\/awac343","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T17:39:38Z","timestamp":1663781978000},"page":"1602-1614","source":"Crossref","is-referenced-by-count":54,"title":["Measures of cortical microstructure are linked to amyloid pathology in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5404-8788","authenticated-orcid":false,"given":"Nicola","family":"Spotorno","sequence":"first","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences, Lund University , Malm\u00f6, Lund 223 62 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Strandberg","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences, Lund University , Malm\u00f6, Lund 223 62 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraline","family":"Vis","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, Department of Clinical Sciences, Lund University , 221 85 Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stomrud","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences, Lund University , Malm\u00f6, Lund 223 62 , Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital , 214 28 Malm\u00f6 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, Department of Clinical Sciences, Lund University , 221 85 Lund , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-7286","authenticated-orcid":false,"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[{"name":"Clinical Memory Research Unit, Department of Clinical Sciences, Lund University , Malm\u00f6, Lund 223 62 , Sweden"},{"name":"Memory Clinic, Sk\u00e5ne University Hospital , 214 28 Malm\u00f6 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"2023041916382385100_awac343-B1","doi-asserted-by":"crossref","first-page":"15056","DOI":"10.1038\/nrdp.2015.56","article-title":"Alzheimer\u2019s disease","volume":"1","author":"Masters","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"2023041916382385100_awac343-B2","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41591-021-01382-x","article-title":"Biomarkers for neurodegenerative 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