{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:09:45Z","timestamp":1792069785118,"version":"4.4.0"},"reference-count":94,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T00:00:00Z","timestamp":1588896000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cambridge Biomedical Research Centre Dementia and Neurodegeneration"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["103838"],"award-info":[{"award-number":["103838"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cambridge Trust & Sidney Sussex College Scholarship"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["SUAG\/04\/G101400"],"award-info":[{"award-number":["SUAG\/04\/G101400"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P01271X\/1"],"award-info":[{"award-number":["MR\/P01271X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cambridge Centre for Parkinson Plus, and British Academy","award":["PF160048"],"award-info":[{"award-number":["PF160048"]}]},{"name":"Department of Health and Social Care"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tau pathology, neuroinflammation, and neurodegeneration are key aspects of Alzheimer\u2019s disease. Understanding whether these features predict cognitive decline, alone or in combination, is crucial to develop new prognostic measures and enhanced stratification for clinical trials. Here, we studied how baseline assessments of in vivo tau pathology (measured by 18F-AV-1451 PET), neuroinflammation (measured by 11C-PK11195 PET) and brain atrophy (derived from structural MRI) predicted longitudinal cognitive changes in patients with Alzheimer\u2019s disease pathology. Twenty-six patients (n\u2009=\u200912 with clinically probable Alzheimer\u2019s dementia and n\u2009=\u200914 with amyloid-positive mild cognitive impairment) and 29 healthy control subjects underwent baseline assessment with 18F-AV-1451 PET, 11C-PK11195 PET, and structural MRI. Cognition was examined annually over the subsequent 3 years using the revised Addenbrooke\u2019s Cognitive Examination. Regional grey matter volumes, and regional binding of 18F-AV-1451 and 11C-PK11195 were derived from 15 temporo-parietal regions characteristically affected by Alzheimer\u2019s disease pathology. A principal component analysis was used on each imaging modality separately, to identify the main spatial distributions of pathology. A latent growth curve model was applied across the whole sample on longitudinal cognitive scores to estimate the rate of annual decline in each participant. We regressed the individuals\u2019 estimated rate of cognitive decline on the neuroimaging components and examined univariable predictive models with single-modality predictors, and a multi-modality predictive model, to identify the independent and combined prognostic value of the different neuroimaging markers. Principal component analysis identified a single component for the grey matter atrophy, while two components were found for each PET ligand: one weighted to the anterior temporal lobe, and another weighted to posterior temporo-parietal regions. Across the whole-sample, the single-modality models indicated significant correlations between the rate of cognitive decline and the first component of each imaging modality. In patients, both stepwise backward elimination and Bayesian model selection revealed an optimal predictive model that included both components of 18F-AV-1451 and the first (i.e. anterior temporal) component for 11C-PK11195. However, the MRI-derived atrophy component and demographic variables were excluded from the optimal predictive model of cognitive decline. We conclude that temporo-parietal tau pathology and anterior temporal neuroinflammation predict cognitive decline in patients with symptomatic Alzheimer\u2019s disease pathology. This indicates the added value of PET biomarkers in predicting cognitive decline in Alzheimer\u2019s disease, over and above MRI measures of brain atrophy and demographic data. Our findings also support the strategy for targeting tau and neuroinflammation in disease-modifying therapy against Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awaa088","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T16:10:55Z","timestamp":1584461455000},"page":"1588-1602","source":"Crossref","is-referenced-by-count":189,"title":["Microglial activation and tau burden predict cognitive decline in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-9656","authenticated-orcid":false,"given":"Maura","family":"Malpetti","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier A","family":"Kievit","sequence":"first","affiliation":[{"name":"MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Passamonti","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"},{"name":"Institute of Molecular Bioimaging and Physiology, National Research Council, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Simon","family":"Jones","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-6363","authenticated-orcid":false,"given":"Kamen A","family":"Tsvetanov","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1063-6937","authenticated-orcid":false,"given":"Timothy","family":"Rittman","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"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, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Nicastro","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, Cambridge, UK"},{"name":"Department of Clinical Neurosciences, Geneva University Hospitals, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Richard","family":"Bevan-Jones","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Su","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young T","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim D","family":"Fryer","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin I","family":"Aigbirhio","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T","family":"O\u2019Brien","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Cambridge, Cambridge, UK"},{"name":"Cambridge University Hospitals NHS Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7216-8679","authenticated-orcid":false,"given":"James B","family":"Rowe","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"},{"name":"MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK"},{"name":"Cambridge University Hospitals NHS Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"key":"2020052115184307300_awaa088-B1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimer\u2019s Dement"},{"key":"2020052115184307300_awaa088-B2","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of microglia and inhibition of exosome synthesis halt tau propagation","volume":"18","author":"Asai","year":"2015","journal-title":"Nat Neurosci"},{"key":"2020052115184307300_awaa088-B3","doi-asserted-by":"crossref","first-page":"e859","DOI":"10.1212\/WNL.0000000000006075","article-title":"Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease","volume":"91","author":"Aschenbrenner","year":"2018","journal-title":"Neurology"},{"key":"2020052115184307300_awaa088-B4","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/glia.10144","article-title":"Visualising microglial activation in vivo","volume":"40","author":"Banati","year":"2002","journal-title":"Glia"},{"key":"2020052115184307300_awaa088-B5","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1093\/brain\/awx243","article-title":"Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer\u2019s disease","volume":"140","author":"Bejanin","year":"2017","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B6","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1177\/0049124187016001004","article-title":"Practical issues in structural modeling","volume":"16","author":"Bentler","year":"1987","journal-title":"Sociol Methods Res"},{"key":"2020052115184307300_awaa088-B7","doi-asserted-by":"crossref","first-page":"e013187","DOI":"10.1136\/bmjopen-2016-013187","article-title":"Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses","volume":"7","author":"Bevan-Jones","year":"2017","journal-title":"BMJ Open"},{"key":"2020052115184307300_awaa088-B8","doi-asserted-by":"crossref","first-page":"338ra66","DOI":"10.1126\/scitranslmed.aaf2362","article-title":"Tau and A\u03b2 imaging, CSF measures, and cognition in Alzheimer\u2019s disease","volume":"8","author":"Brier","year":"2016","journal-title":"Sci Transl Med"},{"key":"2020052115184307300_awaa088-B9","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer\u2019s disease: current evidence and future directions. Alzheimer\u2019s","volume":"12","author":"Calsolaro","year":"2016","journal-title":"Dement"},{"key":"2020052115184307300_awaa088-B10","first-page":"1","author":"Chandra","year":"2019"},{"key":"2020052115184307300_awaa088-B11","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1038\/mp.2017.108","article-title":"Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer\u2019s disease dementia","volume":"23","author":"Chiotis","year":"2018","journal-title":"Mol Psychiatry"},{"key":"2020052115184307300_awaa088-B12","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/ana.24711","article-title":"In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum","volume":"80","author":"Cho","year":"2016","journal-title":"Ann Neurol"},{"key":"2020052115184307300_awaa088-B13","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1212\/WNL.0000000000002892","article-title":"Tau PET in Alzheimer disease and mild cognitive impairment","volume":"87","author":"Cho","year":"2016","journal-title":"Neurology"},{"key":"2020052115184307300_awaa088-B14","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.2967\/jnumed.118.221697","article-title":"Progressive tau accumulation in Alzheimer\u2019s disease: two-year follow-up study","volume":"60","author":"Cho","year":"2019","journal-title":"J Nucl Med"},{"key":"2020052115184307300_awaa088-B15","first-page":"2740","article-title":"Microglial activation correlates in vivo with both tau and amyloid in Alzheimer \u2018s disease","volume":"141","author":"Dani","year":"2018","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B16","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3390\/ijms18040785","article-title":"Translocator protein-18 kDa (TSPO) positron emission tomography (PET) imaging and its clinical impact in neurodegenerative diseases","volume":"18","author":"Dupont","year":"2017","journal-title":"Int J Mol Sci"},{"key":"2020052115184307300_awaa088-B17","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.nbd.2008.08.001","article-title":"Microglia, amyloid, and cognition in Alzheimer\u2019s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study","volume":"32","author":"Edison","year":"2008","journal-title":"Neurobiol Dis"},{"key":"2020052115184307300_awaa088-B18","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jalz.2014.06.016","article-title":"Influence of microglial activation on neuronal function in Alzheimer\u2019s and Parkinson\u2019s disease dementia","volume":"11","author":"Fan","year":"2015","journal-title":"Alzheimer\u2019s Dement"},{"key":"2020052115184307300_awaa088-B19","first-page":"792","article-title":"An early and late peak in microglial activation in Alzheimer\u2019s disease trajectory","volume":"140","author":"Fan","year":"2017","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B20","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1093\/brain\/awv288","article-title":"Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer\u2019s disease","volume":"138","author":"Fan","year":"2015","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B21","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.3233\/JAD-150827","article-title":"Does microglial activation influence hippocampal volume and neuronal function in Alzheimer\u2019s disease and Parkinson\u2019s disease dementia?","volume":"51","author":"Femminella","year":"2016","journal-title":"J Alzheimer's Dis"},{"key":"2020052115184307300_awaa088-B22","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19123702","article-title":"Imaging and molecular mechanisms of Alzheimer\u2019s disease: a review","volume":"19","author":"Femminella","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2020052115184307300_awaa088-B23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nrneurol.2009.215","article-title":"The clinical use of structural MRI in Alzheimer disease","volume":"6","author":"Frisoni","year":"2010","journal-title":"Nat Rev Neurol"},{"key":"2020052115184307300_awaa088-B24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13550-017-0334-8","article-title":"Comparison of four 11C-labeled PET ligands to quantify translocator protein 18 kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176\u2014based on recent publications that measured specific-to-non-displaceable ratios","volume":"7","author":"Fujita","year":"2017","journal-title":"EJNMMI Res"},{"key":"2020052115184307300_awaa088-B25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neurobiolaging.2016.03.033","article-title":"Clinical validity of brain fluorodeoxyglucose positron emission tomography as a biomarker for Alzheimer\u2019s disease in the context of a structured 5-phase development framework","volume":"52","author":"Garibotto","year":"2017","journal-title":"Neurobiol Aging"},{"key":"2020052115184307300_awaa088-B26","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.neuroimage.2007.11.034","article-title":"Automatic segmentation of brain MRIs of 2-year-olds into 83 regions of interest","volume":"40","author":"Gousias","year":"2008","journal-title":"Neuroimage"},{"key":"2020052115184307300_awaa088-B27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/bpa.12763","article-title":"Characterization of the 18 kDa translocator protein (TSPO) expression in post-mortem normal and Alzheimer\u2019s disease brains","volume":"30","author":"Gui","year":"2019","journal-title":"Brain Pathol"},{"key":"2020052115184307300_awaa088-B28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1006\/nimg.1997.0303","article-title":"Parametric imaging of ligand-receptor binding in PET using a simplified reference region model","volume":"6","author":"Gunn","year":"1997","journal-title":"Neuroimage"},{"key":"2020052115184307300_awaa088-B29","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.neuroimage.2011.12.078","article-title":"Identifying improved TSPO PET imaging probes through biomathematics: the impact of multiple TSPO binding sites in vivo","volume":"60","author":"Guo","year":"2012","journal-title":"Neuroimage"},{"key":"2020052115184307300_awaa088-B30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.arr.2017.03.002","article-title":"In vivo tau PET imaging in dementia: pathophysiology, radiotracer quantification, and a systematic review of clinical findings","volume":"36","author":"Hall","year":"2017","journal-title":"Ageing Res Rev"},{"key":"2020052115184307300_awaa088-B31","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1093\/brain\/awy079","article-title":"Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer\u2019s disease","volume":"141","author":"Hamelin","year":"2018","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B32","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/hbm.10123","article-title":"Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe","volume":"19","author":"Hammers","year":"2003","journal-title":"Hum Brain Mapp"},{"key":"2020052115184307300_awaa088-B33","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol"},{"key":"2020052115184307300_awaa088-B34","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.jalz.2015.05.002","article-title":"Magnetic resonance imaging in Alzheimer\u2019s Disease neuroimaging initiative 2. Alzheimer\u2019s","volume":"11","author":"Jack","year":"2015","journal-title":"Dement"},{"key":"2020052115184307300_awaa088-B35","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/brain\/awm336","article-title":"11C PiB and structural MRI provide complementary information in imaging of Alzheimer\u2019s disease and amnestic mild cognitive impairment","volume":"131","author":"Jack","year":"2008","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B36","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1093\/brain\/awy059","article-title":"Longitudinal tau PET in ageing and Alzheimer\u2019s disease","volume":"141","author":"Jack","year":"2018","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B37","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41583-018-0067-3","article-title":"Imaging the evolution and pathophysiology of Alzheimer disease","volume":"19","author":"Jagust","year":"2018","journal-title":"Nat Rev Neurosci"},{"key":"2020052115184307300_awaa088-B38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/ana.24546","article-title":"Tau positron emission tomographic imaging in aging and early Alzheimer disease","volume":"79","author":"Johnson","year":"2016","journal-title":"Ann Neurol"},{"key":"2020052115184307300_awaa088-B39","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1109\/23.34585","article-title":"Analytic 3D image reconstruction using all detected events","volume":"36","author":"Kinahan","year":"1989","journal-title":"IEEE Trans Nucl Sci"},{"key":"2020052115184307300_awaa088-B40","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/ana.20009","article-title":"Imaging brain amyloid in Alzheimer\u2019s disease with Pittsburgh Compound-B","volume":"55","author":"Klunk","year":"2004","journal-title":"Ann Neurol"},{"key":"2020052115184307300_awaa088-B41","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1177\/0271678X17699223","article-title":"11 C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11 C- (R) -PK11195","volume":"38","author":"Kobayashi","year":"2018","journal-title":"J Cereb Blood Flow Metab"},{"key":"2020052115184307300_awaa088-B42","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3233\/JAD-170129","article-title":"PET Tau and Amyloid-\u03b2 Burden in Mild Alzheimer\u2019s Disease: divergent relationship with age, cognition, and cerebrospinal fluid biomarkers","volume":"60","author":"Koychev","year":"2017","journal-title":"J Alzheimer's Dis"},{"key":"2020052115184307300_awaa088-B43","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neurobiolaging.2016.04.011","article-title":"11C-PBR28 binding to translocator protein increases with progression of Alzheimer\u2019s disease","volume":"44","author":"Kreisl","year":"2016","journal-title":"Neurobiol Aging"},{"key":"2020052115184307300_awaa088-B44","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1212\/WNL.0b013e318281ccd3","article-title":"Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration","volume":"80","author":"Leung","year":"2013","journal-title":"Neurology"},{"key":"2020052115184307300_awaa088-B45","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40478-016-0315-6","article-title":"An autoradiographic evaluation of AV-1451 Tau PET in dementia","volume":"4","author":"Lowe","year":"2016","journal-title":"Acta Neuropathol Commun"},{"key":"2020052115184307300_awaa088-B46","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.jalz.2019.09.079","article-title":"Tau-positron emission tomography correlates with neuropathology findings [Internet]","volume":"16","author":"Lowe","year":"2020","journal-title":"Alzheimer\u2019s Dement"},{"key":"2020052115184307300_awaa088-B47","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1523\/JNEUROSCI.2028-17.2017","article-title":"Entorhinal tau pathology, episodic memory decline, and neurodegeneration in aging","volume":"38","author":"Maass","year":"2018","journal-title":"J Neurosci"},{"key":"2020052115184307300_awaa088-B48","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/brain\/awv081","article-title":"Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain","volume":"138","author":"Maphis","year":"2015","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B49","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/ana.24517","article-title":"Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue","volume":"78","author":"Marqui\u00e9","year":"2015","journal-title":"Ann Neurol"},{"key":"2020052115184307300_awaa088-B50","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jalz.2018.12.001","article-title":"Predicting diagnosis and cognition with 18 F-AV-1451 tau PET and structural MRI in Alzheimer\u2019s disease. Alzheimer\u2019s","volume":"15","author":"Mattsson","year":"2019","journal-title":"Dement"},{"key":"2020052115184307300_awaa088-B51","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimer\u2019s","volume":"7","author":"McKhann","year":"2011","journal-title":"Dement"},{"key":"2020052115184307300_awaa088-B52","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/YCO.0000000000000482","article-title":"Understanding and predicting the longitudinal course of dementia","volume":"32","author":"Melis","year":"2019","journal-title":"Curr Opin Psychiatry"},{"key":"2020052115184307300_awaa088-B53","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.tins.2015.08.006","article-title":"Microglial Malfunction: the Third Rail in the Development of Alzheimer\u2019s Disease","volume":"38","author":"Mhatre","year":"2015","journal-title":"Trends Neurosci"},{"key":"2020052115184307300_awaa088-B54","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/gps.1610","article-title":"The Addenbrooke\u2019s Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening","volume":"21","author":"Mioshi","year":"2006","journal-title":"Int J Geriat Psychiatry"},{"key":"2020052115184307300_awaa088-B55","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/NEN.0b013e31825018f7","article-title":"Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: a Review of the Literature","volume":"71","author":"Nelson","year":"2012","journal-title":"J Neuropathol Exp Neurol"},{"key":"2020052115184307300_awaa088-B56","doi-asserted-by":"crossref","DOI":"10.4324\/9781315871318","volume-title":"Longitudinal structural equation modeling: a comprehensive introduction","author":"Newsom","year":"2015"},{"key":"2020052115184307300_awaa088-B57","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1212\/01.wnl.0000338622.27876.0d","article-title":"Microglial activation and amyloid deposition in mild cognitive impairment: a PET study","volume":"72","author":"Okello","year":"2009","journal-title":"Neurology"},{"key":"2020052115184307300_awaa088-B58","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1212\/WNL.0b013e3181b23564","article-title":"Conversion of amyloid positive and negative mci to ad over 3 years: an c-pib pet study symbol","volume":"73","author":"Okello","year":"2009","journal-title":"Neurology"},{"key":"2020052115184307300_awaa088-B59","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1093\/brain\/aww027","article-title":"Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer\u2019s disease","volume":"139","author":"Ossenkoppele","year":"2016","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/jcbfm.2011.147","article-title":"An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28","volume":"32","author":"Owen","year":"2012","journal-title":"J Cereb Blood Flow Metab"},{"key":"2020052115184307300_awaa088-B61","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.nbd.2018.06.004","article-title":"Does inflammation precede tau aggregation in early Alzheimer\u2019s disease? A PET study","volume":"117","author":"Parbo","year":"2018","journal-title":"Neurobiol Dis"},{"key":"2020052115184307300_awaa088-B62","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s11910-015-0531-7","article-title":"The Role of Neuroinflammation in Dementias","volume":"15","author":"Pasqualetti","year":"2015","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2020052115184307300_awaa088-B63","doi-asserted-by":"crossref","first-page":"e1989","DOI":"10.1212\/WNL.0000000000005610","article-title":"11 CPK11195 binding in Alzheimer disease and progressive supranuclear palsy","volume":"90","author":"Passamonti","year":"2018","journal-title":"Neurology"},{"key":"2020052115184307300_awaa088-B64","doi-asserted-by":"crossref","first-page":"7218","DOI":"10.1523\/JNEUROSCI.2574-18.2019","article-title":"Neuroinflammation and functional connectivity in Alzheimer\u2019s Disease: interactive influences on cognitive performance","volume":"39","author":"Passamonti","year":"2019","journal-title":"J Neurosci"},{"key":"2020052115184307300_awaa088-B65","first-page":"781","article-title":"18 F-AV-1451 positron emission tomography in Alzheimer\u2019s disease and progressive supranuclear palsy","volume":"140","author":"Passamonti","year":"2017","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fncel.2018.00172","article-title":"The Role of Microglia in the Spread of Trelevance for Tauopathies","volume":"12","author":"Perea","year":"2018","journal-title":"Front Cell Neurosci"},{"key":"2020052115184307300_awaa088-B67","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1093\/brain\/awz090","article-title":"A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer\u2019s disease dementia","volume":"142","author":"Pontecorvo","year":"2019","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B68","first-page":"748","article-title":"Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition","volume":"140","author":"Pontecorvo","year":"2017","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B69","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1126\/science.aag2590","article-title":"How neuroinflammation contributes to neurodegeneration","volume":"353","author":"Ransohoff","year":"2016","journal-title":"Science"},{"key":"2020052115184307300_awaa088-B70","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1093\/cercor\/bhi044","article-title":"Regional brain changes in aging healthy adults: general trends, individual differences and modifiers","volume":"15","author":"Raz","year":"2005","journal-title":"Cereb Cortex"},{"key":"2020052115184307300_awaa088-B71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v048.i02","article-title":"lavaan: an R Package for Structural Equation Modeling","volume":"48","author":"Rosseel","year":"2012","journal-title":"J Stat Softw"},{"key":"2020052115184307300_awaa088-B72","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.jalz.2016.01.003","article-title":"Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer\u2019s disease, primary tauopathies, and other dementias. Alzheimer\u2019s","volume":"12","author":"Sander","year":"2016","journal-title":"Dement"},{"key":"2020052115184307300_awaa088-B73","doi-asserted-by":"crossref","first-page":"677","DOI":"10.2967\/jnumed.110.086629","article-title":"The translocator protein","volume":"52","author":"Scarf","year":"2011","journal-title":"J Nucl Med"},{"key":"2020052115184307300_awaa088-B74","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11910-017-0733-2","article-title":"Neuroinflammation in neurodegenerative disorders\u2014a review","volume":"17","author":"Schain","year":"2017","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2020052115184307300_awaa088-B75","first-page":"23","article-title":"Evaluating the fit of structural equation models: tests of significance and descriptive goodness-of-fit measures","volume":"8","author":"Schermelleh-Engel","year":"2003","journal-title":"Methods Psychol Res"},{"key":"2020052115184307300_awaa088-B76","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.neuron.2016.01.028","article-title":"PET imaging of tau deposition in the aging human brain","volume":"89","author":"Sch\u00f6ll","year":"2016","journal-title":"Neuron"},{"key":"2020052115184307300_awaa088-B77","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mcn.2018.12.001","article-title":"Biomarkers for tau pathology","volume":"97","author":"Sch\u00f6ll","year":"2019","journal-title":"Mol Cell Neurosci"},{"key":"2020052115184307300_awaa088-B78","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1093\/brain\/aww023","article-title":"Regional profiles of the candidate tau PET ligand18F-AV-1451 recapitulate key features of Braak histopathological stages","volume":"139","author":"Schwarz","year":"2016","journal-title":"Brain"},{"key":"2020052115184307300_awaa088-B79","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1001\/jamaneurol.2018.3692","article-title":"Correlation of in Vivo [18 F]Flortaucipir with postmortem Alzheimer disease tau pathology","volume":"76","author":"Smith","year":"2019","journal-title":"JAMA Neurol"},{"key":"2020052115184307300_awaa088-B80","doi-asserted-by":"crossref","first-page":"944","DOI":"10.2967\/jnumed.117.200006","article-title":"Flortaucipir F 18 quantitation using parametric estimation of reference signal intensity","volume":"59","author":"Southekal","year":"2018","journal-title":"J Nucl Med"},{"key":"2020052115184307300_awaa088-B81","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.neuron.2014.05.004","article-title":"The intersection of amyloid beta and tau at synapses in Alzheimer\u2019s disease","volume":"82","author":"Spires-Jones","year":"2014","journal-title":"Neuron"},{"key":"2020052115184307300_awaa088-B82","first-page":"21","article-title":"Imaging of neuroinflammation in dementia: a review","volume":"87","author":"Stefaniak","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2020052115184307300_awaa088-B83","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1007\/s00415-019-09400-2","article-title":"In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer\u2019s disease [Internet","volume":"266","author":"Terada","year":"2019","journal-title":"J Neurol"},{"key":"2020052115184307300_awaa088-B84","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13195-019-0510-3","article-title":"Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer\u2019s disease spectrum","volume":"11","author":"Timmers","year":"2019","journal-title":"Alzheimers Res Ther"},{"key":"2020052115184307300_awaa088-B85","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1474-4422(13)70044-9","article-title":"Amyloid \u03b2 deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer\u2019s disease: A prospective cohort study","volume":"12","author":"Villemagne","year":"2013","journal-title":"Lancet Neurol"},{"key":"2020052115184307300_awaa088-B86","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/ana.22248","article-title":"Longitudinal assessment of A\u03b2 and cognition in aging and Alzheimer disease","volume":"69","author":"Villemagne","year":"2011","journal-title":"Ann Neurol"},{"key":"2020052115184307300_awaa088-B87","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2967\/jnumed.114.141713","article-title":"Imaging Microglial Activation with TSPO PET: lighting up neurologic diseases?","volume":"57","author":"Vivash","year":"2016","journal-title":"J Nucl Med"},{"key":"2020052115184307300_awaa088-B88","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.neurobiolaging.2009.05.013","article-title":"Consistent neuroanatomical age-related volume differences across multiple samples","volume":"32","author":"Walhovd","year":"2011","journal-title":"Neurobiol Aging"},{"key":"2020052115184307300_awaa088-B89","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1097\/WCO.0000000000000570","article-title":"Alzheimer \u2018s disease neuroimaging","volume":"31","author":"Whitwell","year":"2018","journal-title":"Curr Opin Neurol"},{"key":"2020052115184307300_awaa088-B90","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.jalz.2012.11.008","article-title":"18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer\u2019s disease. Alzheimer\u2019s","volume":"9","author":"Xia","year":"2013","journal-title":"Dement"},{"key":"2020052115184307300_awaa088-B91","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1038\/jcbfm.2012.59","article-title":"Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies","volume":"32","author":"Yaqub","year":"2012","journal-title":"J Cereb Blood Flow Metab"},{"key":"2020052115184307300_awaa088-B92","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s00259-010-1612-0","article-title":"In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer\u2019s disease","volume":"38","author":"Yokokura","year":"2011","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2020052115184307300_awaa088-B93","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","article-title":"Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model","volume":"53","author":"Yoshiyama","year":"2007","journal-title":"Neuron"},{"key":"2020052115184307300_awaa088-B94","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neurobiolaging.2019.09.019","article-title":"Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment","volume":"85","author":"Zou","year":"2020","journal-title":"Neurobiol Aging"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/5\/1588\/33281793\/awaa088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/5\/1588\/33281793\/awaa088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T15:25:28Z","timestamp":1590074728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/143\/5\/1588\/5831943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,1]]},"references-count":94,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5,7]]},"published-print":{"date-parts":[[2020,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awaa088","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/19011189","asserted-by":"object"}]},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5]]},"published":{"date-parts":[[2020,5,1]]}}}