{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:15:43Z","timestamp":1790820943948,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"the Medical Research Council","doi-asserted-by":"crossref","award":["98480"],"award-info":[{"award-number":["98480"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Alzheimer\u2019s Society Junior Research Fellowship","award":["RG9611; 443 JF-18-017"],"award-info":[{"award-number":["RG9611; 443 JF-18-017"]}]},{"DOI":"10.13039\/501100000272","name":"the National Institute for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Cambridge Biomedical Research Centre"},{"name":"the National Institute for Health Research Collaborations in Leadership for Applied Health Research and Care for the East of England"},{"name":"the National Institute for Health Research Cambridge Dementia Biomedical Research Unit"},{"name":"the Down Syndrome Association"},{"DOI":"10.13039\/501100000724","name":"the Health Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000724","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Positron emission tomography imaging of glucose hypometabolism and amyloid deposition are two well-established methods to evaluate preclinical changes in Alzheimer\u2019s disease and people with Down syndrome. However, the use of both imaging modalities may overburden participants, particularly those with intellectual disabilities and cognitive impairment. The relative tracer delivery of the [11C]-Pittsburgh Compound B has been proposed as a viable surrogate for cerebral perfusion. Here, we studied the impact of amyloid pathology on perfusion changes in Down syndrome and evaluated its associations with cognitive impairment. In total, 47 adults with Down syndrome underwent the [11C]-Pittsburgh Compound B imaging and structural imaging. The structural data were processed with Freesurfer to obtain anatomical segmentations and cortical thickness. The relative tracer delivery from [11C]-Pittsburgh Compound B was derived using a simplified reference tissue model. The sample was stratified into those with minimal amyloid burden (n\u2009=\u200925) and those with elevated amyloid (n\u2009=\u200922). We found significant and widespread reductions of cerebral perfusion in those with elevated amyloid burden, independent of age, gender, cognitive function and cortical thickness. In addition, cerebral perfusion was associated with the cognitive impairment among the Down syndrome group with elevated amyloid burden. These findings highlight the promising utility of the relative tracer delivery of the [11C]-Pittsburgh Compound B as a surrogate index in clinical trials for monitoring disease progression or tracking physiologic changes over time in Down syndrome.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa198","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T14:38:17Z","timestamp":1605710297000},"source":"Crossref","is-referenced-by-count":5,"title":["Measuring cerebral perfusion with [11C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-8024","authenticated-orcid":false,"given":"Elijah","family":"Mak","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Grigorova","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Beresford-Webb","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9656","authenticated-orcid":false,"given":"Maura","family":"Malpetti","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0SZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Walpert","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Clare","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young T","family":"Hong","sequence":"additional","affiliation":[{"name":"Wolfson Brain Imaging Centre, University of Cambridge, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim D","family":"Fryer","sequence":"additional","affiliation":[{"name":"Wolfson Brain Imaging Centre, University of Cambridge, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P","family":"Coles","sequence":"additional","affiliation":[{"name":"Division of Anaesthesia, University of Cambridge, Cambridge, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin I","family":"Aigbirhio","sequence":"additional","affiliation":[{"name":"Wolfson Brain Imaging Centre, University of Cambridge, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K","family":"Menon","sequence":"additional","affiliation":[{"name":"Division of Anaesthesia, University of Cambridge, Cambridge, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Nestor","sequence":"additional","affiliation":[{"name":"Queensland Brain Institute, University of Queensland, Queensland, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Holland","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahid H","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"2021013108352754000_fcaa198-B1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neurobiolaging.2017.01.009","article-title":"The Down syndrome brain in the presence and absence of fibrillar \u03b2-amyloidosis","volume":"53","author":"Annus","year":"2017","journal-title":"Neurobiol Aging"},{"key":"2021013108352754000_fcaa198-B2","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.jalz.2015.07.490","article-title":"The pattern of amyloid accumulation in the brains of adults with Down syndrome","volume":"12","author":"Annus","year":"2016","journal-title":"Alzheimers Dement"},{"key":"2021013108352754000_fcaa198-B3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa1202753","article-title":"Clinical and biomarker changes in dominantly inherited Alzheimer\u2019s disease","volume":"367","author":"Bateman","year":"2012","journal-title":"N Engl J Med"},{"key":"2021013108352754000_fcaa198-B4","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.2967\/jnumed.114.152405","article-title":"Relative 11C-PiB delivery as a proxy of relative CBF: quantitative evaluation using single-session 15O-water and 11C-PiB PET","volume":"56","author":"Chen","year":"2015","journal-title":"J Nucl Med"},{"key":"2021013108352754000_fcaa198-B5","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"Desikan","year":"2006","journal-title":"Neuroimage"},{"key":"2021013108352754000_fcaa198-B6","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1007\/s00259-003-1194-1","article-title":"Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer\u2019s disease: a PET follow-up study","volume":"30","author":"Drzezga","year":"2003","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2021013108352754000_fcaa198-B7","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1093\/brain\/awl178","article-title":"Two-year follow-up of amyloid deposition in patients with Alzheimer\u2019s disease","volume":"129","author":"Engler","year":"2006","journal-title":"Brain"},{"key":"2021013108352754000_fcaa198-B8","doi-asserted-by":"crossref","first-page":"11050","DOI":"10.1073\/pnas.200033797","article-title":"Measuring the thickness of the human cerebral cortex from magnetic resonance images","volume":"97","author":"Fischl","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021013108352754000_fcaa198-B9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.neuroimage.2015.03.005","article-title":"Fast and powerful heritability inference for family-based neuroimaging studies","volume":"115","author":"Ganjgahi","year":"2015","journal-title":"Neuroimage"},{"key":"2021013108352754000_fcaa198-B10","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1212\/01.WNL.0000098935.36984.25","article-title":"Temporal cortex hypermetabolism in Down syndrome prior to the onset of dementia","volume":"61","author":"Haier","year":"2003","journal-title":"Neurology"},{"key":"2021013108352754000_fcaa198-B11","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1093\/brain\/awu173","article-title":"Cognitive functioning in relation to brain amyloid-\u03b2 in healthy adults with Down syndrome","volume":"137","author":"Hartley","year":"2014","journal-title":"Brain"},{"key":"2021013108352754000_fcaa198-B12","first-page":"5539","article-title":"Shared genetic factors influence head motion during MRI and body mass index","volume":"27","author":"Hodgson","year":"2017","journal-title":"Cereb Cortex"},{"key":"2021013108352754000_fcaa198-B13","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.neuron.2013.12.003","article-title":"Biomarker modeling of Alzheimer\u2019s disease","volume":"80","author":"Jack","year":"2013","journal-title":"Neuron"},{"key":"2021013108352754000_fcaa198-B14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer\u2019s disease: an updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack","year":"2013","journal-title":"Lancet Neurol"},{"key":"2021013108352754000_fcaa198-B15","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1212\/WNL.0000000000001212","article-title":"Age dependence of brain \u03b2-amyloid deposition in Down syndrome: an [18F]florbetaben PET study","volume":"84","author":"Jennings","year":"2015","journal-title":"Neurology"},{"key":"2021013108352754000_fcaa198-B16","first-page":"669","article-title":"Utility of perfusion PET measures to assess neuronal injury in Alzheimer\u2019s disease. Alzheimer\u2019s dement diagnosis","volume":"10","author":"Joseph-Mathurin","year":"2018","journal-title":"Alzheimers Dement"},{"key":"2021013108352754000_fcaa198-B17","first-page":"1","article-title":"Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population","volume":"9","author":"Lao","year":"2017","journal-title":"Alzheimers Dement"},{"key":"2021013108352754000_fcaa198-B18","doi-asserted-by":"crossref","first-page":"631","DOI":"10.3233\/JAD-170720","article-title":"Alzheimer-like pattern of hypometabolism emerges with elevated amyloid-\u03b2 burden in Down syndrome","volume":"61","author":"Lao","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"2021013108352754000_fcaa198-B19","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.neurobiolaging.2019.02.018","article-title":"Delineating the topography of amyloid-associated cortical atrophy in Down\u2019s syndrome","volume":"80","author":"Mak","year":"2019","journal-title":"Neurobiol Aging"},{"key":"2021013108352754000_fcaa198-B20","first-page":"654","article-title":"Longitudinal trajectories of amyloid deposition, cortical thickness and tau deposition in Down syndrome: a deep-phenotyping case report","volume":"11","author":"Mak","year":"2019","journal-title":"Alzheimer\u2019s & Dement"},{"key":"2021013108352754000_fcaa198-B21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.trci.2016.02.004","article-title":"Dissociation of Down syndrome and Alzheimer\u2019s disease effects with imaging","volume":"2","author":"Matthews","year":"2016","journal-title":"Alzheimers Dement Transl Res Clin Interv"},{"key":"2021013108352754000_fcaa198-B22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2967\/jnumed.110.083683","article-title":"Dual-biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh Compound B","volume":"52","author":"Meyer","year":"2011","journal-title":"J Nucl Med"},{"key":"2021013108352754000_fcaa198-B23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ana.410420114","article-title":"Metabolic reduction in the posterior cingulate cortex in very early Alzheimer\u2019s disease","volume":"42","author":"Minoshima","year":"1997","journal-title":"Ann Neurol"},{"key":"2021013108352754000_fcaa198-B24","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/s00259-005-1762-7","article-title":"Brain glucose metabolism in the early and specific diagnosis of Alzheimer\u2019s disease","volume":"32","author":"Mosconi","year":"2005","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2021013108352754000_fcaa198-B25","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00259-008-1039-z","article-title":"FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer\u2019s disease","volume":"36","author":"Mosconi","year":"2009","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2021013108352754000_fcaa198-B26","first-page":"1778","article-title":"Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer\u2019s disease","volume":"47","author":"Mosconi","year":"2006","journal-title":"J Nucl Med"},{"key":"2021013108352754000_fcaa198-B27","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.nicl.2017.10.022","article-title":"Neuroimaging and other modalities to assess Alzheimer\u2019s disease in Down syndrome","volume":"17","author":"Neale","year":"2018","journal-title":"NeuroImage Clin"},{"key":"2021013108352754000_fcaa198-B28","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/ana.10669","article-title":"Limbic hypometabolism in Alzheimer\u2019s disease and mild cognitive impairment","volume":"54","author":"Nestor","year":"2003","journal-title":"Ann Neurol"},{"key":"2021013108352754000_fcaa198-B29","article-title":"18F-FDG PET imaging","author":"Ottoy","year":"2019","journal-title":"NeuroImage Clin"},{"key":"2021013108352754000_fcaa198-B30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/jcbfm.2009.188","article-title":"Cerebral blood flow response to functional activation","volume":"30","author":"Paulson","year":"2010","journal-title":"J Cereb Blood Flow Metab"},{"key":"2021013108352754000_fcaa198-B31","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1001\/2013.jamaneurol.286","article-title":"Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for Alzheimer disease","volume":"70","author":"Protas","year":"2013","journal-title":"JAMA Neurol"},{"key":"2021013108352754000_fcaa198-B32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neurobiolaging.2014.11.008","article-title":"Heritability and genetic association analysis of neuroimaging measures in the Diabetes Heart Study","volume":"36","author":"Raffield","year":"2015","journal-title":"Neurobiol Aging"},{"key":"2021013108352754000_fcaa198-B33","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1192\/bjp.149.6.698","article-title":"CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia","volume":"149","author":"Roth","year":"1986","journal-title":"Br J Psychiatry"},{"key":"2021013108352754000_fcaa198-B34","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.jalz.2015.01.006","article-title":"Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer\u2019s dementia","volume":"11","author":"Sabbagh","year":"2015","journal-title":"Alzheimers Dement"},{"key":"2021013108352754000_fcaa198-B35","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0197-4580(01)00230-5","article-title":"Hippocampal formation glucose metabolism and volume losses in MCI and AD","volume":"22","author":"De Santi","year":"2001","journal-title":"Neurobiol Aging"},{"key":"2021013108352754000_fcaa198-B36","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/jcbfm.1990.35","article-title":"Regional cerebral glucose metabolism is normal in young adults with Down syndrome","volume":"10","author":"Schapiro","year":"1990","journal-title":"J Cereb Blood Flow Metab"},{"key":"2021013108352754000_fcaa198-B37","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jalz.2018.01.003","article-title":"Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer\u2019s disease: a prospective study in eight cohorts","volume":"14","author":"Tynkkynen","year":"2018","journal-title":"Alzheimers Dement"},{"key":"2021013108352754000_fcaa198-B38","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1001\/jamaneurol.2016.2078","article-title":"Evaluation of tau imaging in staging Alzheimer disease and revealing interactions between \u03b2-amyloid and tauopathy","volume":"73","author":"Wang","year":"2016","journal-title":"JAMA Neurol"},{"key":"2021013108352754000_fcaa198-B40","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrn3983","article-title":"A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome","volume":"16","author":"Wiseman","year":"2015","journal-title":"Nat Rev Neurosci"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcaa198\/34379387\/fcaa198.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/braincomms\/article-pdf\/3\/1\/fcaa198\/36157566\/fcaa198.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/braincomms\/article-pdf\/3\/1\/fcaa198\/36157566\/fcaa198.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T08:35:56Z","timestamp":1612082156000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcaa198\/5988720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,18]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,16]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcaa198","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021]]},"published":{"date-parts":[[2020,11,18]]},"article-number":"fcaa198"}}