{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:04:55Z","timestamp":1791990295372,"version":"4.4.0"},"reference-count":112,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30-AG062422"],"award-info":[{"award-number":["P30-AG062422"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Disease Research Center","award":["P01-AG019724"],"award-info":[{"award-number":["P01-AG019724"]}]},{"name":"Alzheimer\u2019s Disease Research Center","award":["R35-AG072362"],"award-info":[{"award-number":["R35-AG072362"]}]},{"name":"Alzheimer\u2019s Disease Research Center","award":["K99 AG065501"],"award-info":[{"award-number":["K99 AG065501"]}]},{"name":"Alzheimer\u2019s Disease Research Center","award":["R01 AG045611"],"award-info":[{"award-number":["R01 AG045611"]}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","award":["AACSF-19-617663"],"award-info":[{"award-number":["AACSF-19-617663"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016608","name":"Rainwater Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Race Against Dementia Alzheimer\u2019s Research UK","award":["ARUK-RADF2021A-010"],"award-info":[{"award-number":["ARUK-RADF2021A-010"]}]},{"name":"Cambridge University Centre for Parkinson-Plus","award":["RG95450"],"award-info":[{"award-number":["RG95450"]}]},{"DOI":"10.13039\/501100018956","name":"National Institute for Health Research Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["BRC-1215-20014"],"award-info":[{"award-number":["BRC-1215-20014"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Early-onset (age &amp;lt; 65) Alzheimer\u2019s disease is associated with greater non-amnestic cognitive symptoms and neuropathological burden than late-onset disease. It is not fully understood whether these groups also differ in the associations between molecular pathology, neurodegeneration and cognitive performance.<\/jats:p>\n                  <jats:p>We studied amyloid-positive patients with early-onset (n = 60, mean age 58 \u00b1 4, MMSE 21 \u00b1 6, 58% female) and late-onset (n = 53, mean age 74 \u00b1 6, MMSE 23 \u00b1 5, 45% female) Alzheimer\u2019s disease who underwent neurological evaluation, neuropsychological testing, 11C-Pittsburgh compound B PET (amyloid-PET) and 18F-flortaucipir PET (tau-PET). 18F-fluorodeoxyglucose PET (brain glucose metabolism PET) was also available in 74% (n = 84) of participants. Composite scores for episodic memory, semantic memory, language, executive function and visuospatial domains were calculated based on cognitively unimpaired controls. Voxel-wise regressions evaluated correlations between PET biomarkers and cognitive scores and early-onset versus late-onset differences were tested with a PET \u00d7 Age group interaction. Mediation analyses estimated direct and indirect (18F-fluorodeoxyglucose mediated) local associations between 18F-flortaucipir binding and cognitive scores in domain-specific regions of interest.<\/jats:p>\n                  <jats:p>We found that early-onset patients had higher 18F-flortaucipir binding in parietal, lateral temporal and lateral frontal cortex; more severe 18F-fluorodeoxyglucose hypometabolism in the precuneus and angular gyrus; and greater 11C-Pittsburgh compound B binding in occipital regions compared to late-onset patients. In our primary analyses, PET\u2013cognition correlations did not meaningfully differ between age groups.18F-flortaucipir and 18F-fluorodeoxyglucose, but not 11C-Pittsburgh compound B, were significantly associated with cognition in expected domain-specific patterns in both age groups (e.g. left perisylvian\/language, frontal\/executive, occipital\/visuospatial). 18F-fluorodeoxyglucose mediated the relationship between 18F-flortaucipir and cognition in both age groups across all domains except episodic memory in late-onset patients. Additional direct effects of 18F-flortaucipir were observed for executive function in all age groups, language in early-onset Alzheimer\u2019s disease and in the total sample and visuospatial function in the total sample.<\/jats:p>\n                  <jats:p>In conclusion, tau and neurodegeneration, but not amyloid, were similarly associated with cognition in both early and late-onset Alzheimer\u2019s disease. Tau had an association with cognition independent of neurodegeneration in language, executive and visuospatial functions in the total sample. Our findings support tau PET as a biomarker that captures both the clinical severity and molecular pathology specific to Alzheimer\u2019s disease across the broad spectrum of ages and clinical phenotypes in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awac229","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T09:23:29Z","timestamp":1656408209000},"page":"4489-4505","source":"Crossref","is-referenced-by-count":97,"title":["Amyloid, tau and metabolic PET correlates of cognition in early and late-onset Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-1776","authenticated-orcid":false,"given":"Jeremy A","family":"Tanner","sequence":"first","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0053-9519","authenticated-orcid":false,"given":"Leonardo","family":"Iaccarino","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Edwards","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8419-142X","authenticated-orcid":false,"given":"Breton M","family":"Asken","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L","family":"Gorno-Tempini","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H","family":"Kramer","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Pham","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Perry","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Possin","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9656","authenticated-orcid":false,"given":"Maura","family":"Malpetti","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"},{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Mellinger","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L","family":"Miller","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-3053","authenticated-orcid":false,"given":"Zachary","family":"Miller","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi S","family":"Mundada","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J","family":"Rosen","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4197-3039","authenticated-orcid":false,"given":"David N","family":"Soleimani-Meigooni","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Strom","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco (UCSF) , San Francisco, CA 94158 , 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