{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:16:37Z","timestamp":1787163397130,"version":"build-2736575974"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG040042"],"award-info":[{"award-number":["R01 AG040042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG11378"],"award-info":[{"award-number":["R01 AG11378"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AG16574"],"award-info":[{"award-number":["P50 AG16574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AG06786"],"award-info":[{"award-number":["U01 AG06786"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["C06 RR018898"],"award-info":[{"award-number":["C06 RR018898"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation Dr Corinne Schulerand"},{"name":"Mangurian Foundation for Lewy Body Research"},{"DOI":"10.13039\/100016293","name":"The Elsie and Marvin Dekelboum Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016293","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer\u2019s Disease Research Program"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012295","name":"Newcastle Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012295","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tyne Hospitals NHS Foundation Trust"},{"DOI":"10.13039\/501100000774","name":"Newcastle University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dementia with Lewy bodies (DLB) is neuropathologically defined by the presence of \u03b1-synuclein aggregates, but many DLB cases show concurrent Alzheimer\u2019s disease pathology in the form of amyloid-\u03b2 plaques and tau neurofibrillary tangles.<\/jats:p>\n                  <jats:p>The first objective of this study was to investigate the effect of Alzheimer\u2019s disease co-pathology on functional network changes within the default mode network (DMN) in DLB. Second, we studied how the distribution of tau pathology measured with PET relates to functional connectivity in DLB. Twenty-seven DLB, 26 Alzheimer\u2019s disease and 99 cognitively unimpaired participants (balanced on age and sex to the DLB group) underwent tau-PET with AV-1451 (flortaucipir), amyloid-\u03b2-PET with Pittsburgh compound-B (PiB) and resting-state functional MRI scans. The resing-state functional MRI data were used to assess functional connectivity within the posterior DMN. This was then correlated with overall cortical flortaucipir PET and PiB PET standardized uptake value ratio (SUVr). The strength of interregional functional connectivity was assessed using the Schaefer atlas. Tau-PET covariance was measured as the correlation in flortaucipir SUVr between any two regions across participants. The association between region-to-region functional connectivity and tau-PET covariance was assessed using linear regression. Additionally, we identified the region with highest and the region with lowest tau SUVrs (tau hot- and cold spots) and tested whether tau SUVr in all other brain regions was associated with the strength of functional connectivity to these tau hot and cold spots.<\/jats:p>\n                  <jats:p>A reduction in posterior DMN connectivity correlated with overall higher cortical tau- (r\u2009=\u2009\u22120.39, P\u2009=\u20090.04) and amyloid-PET uptake (r\u2009=\u2009\u22120.41, P\u2009=\u20090.03) in the DLB group, i.e. patients with DLB who have more concurrent Alzheimer\u2019s disease pathology showed a more severe loss of DMN connectivity. Higher functional connectivity between regions was associated with higher tau covariance in cognitively unimpaired, Alzheimer\u2019s disease and DLB. Furthermore, higher functional connectivity of a target region to the tau hotspot (i.e. inferior\/medial temporal cortex) was related to higher flortaucipir SUVrs in the target region, whereas higher functional connectivity to the tau cold spot (i.e. sensory-motor cortex) was related to lower flortaucipir SUVr in the target region.<\/jats:p>\n                  <jats:p>Our findings suggest that a higher burden of Alzheimer\u2019s disease co-pathology in patients with DLB is associated with more Alzheimer\u2019s disease-like changes in functional connectivity. Furthermore, we found an association between the brain\u2019s functional network architecture and the distribution of tau pathology that has recently been described in Alzheimer\u2019s disease. We show that this relationship also exists in patients with DLB, indicating that similar mechanisms of connectivity-dependent occurrence of tau pathology might be at work in both diseases.<\/jats:p>","DOI":"10.1093\/brain\/awab218","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T07:45:26Z","timestamp":1623224726000},"page":"3212-3225","source":"Crossref","is-referenced-by-count":51,"title":["Dementia with Lewy bodies: association of Alzheimer pathology with functional connectivity networks"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7323-4789","authenticated-orcid":false,"given":"Julia","family":"Schumacher","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK"},{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L","family":"Gunter","sequence":"additional","affiliation":[{"name":"Department of Information Technology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A","family":"Przybelski","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2770-0691","authenticated-orcid":false,"given":"Jonathan","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Savica","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L","family":"Senjem","sequence":"additional","affiliation":[{"name":"Department of Information Technology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Clifford R","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Knopman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter K","family":"Kremers","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neill R","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanis J","family":"Ferman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-8187","authenticated-orcid":false,"given":"Bradley F","family":"Boeve","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J","family":"Thomas","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John-Paul","family":"Taylor","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, 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