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1. Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients

Author

Biesbroek, J Matthijs, Coenen, Mirthe, DeCarli, Charles, Fletcher, Evan M, Maillard, Pauline M, Initiative, Alzheimer's Disease Neuroimaging, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Chen, Christopher PLH, Dal‐Bianco, Peter, Dewenter, Anna, Duering, Marco, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Hilal, Saima, Hofer, Edith, Koek, Huiberdina L, Maier, Andrea B, McCreary, Cheryl R, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande AL, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Sudre, Carole H, Steketee, Rebecca ME, Teunissen, Charlotte E, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Venkatraghavan, Vikram, Vernooij, Meike W, Wolters, Frank J, Xin, Xu, Kuijf, Hugo J, and Biessels, Geert Jan

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Vascular Cognitive Impairment/Dementia, Brain Disorders, Clinical Research, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease Related Dementias (ADRD), Aging, Dementia, Cerebrovascular, Alzheimer's Disease, Neurodegenerative, Neurological, Humans, Female, Middle Aged, Aged, Aged, 80 and over, Male, White Matter, Arteriolosclerosis, Amyloid beta-Peptides, Magnetic Resonance Imaging, amyloid pathology, arteriolosclerosis, dementia, lesion pattern, white matter hyperintensities, Alzheimer's Disease Neuroimaging Initiative, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionWhite matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status.MethodsIndividual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume.ResultsVRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p

Published
2024

2. Human SARS-CoV-2 challenge uncovers local and systemic response dynamics

Author

Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.

Published
2024
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3. Updating the study protocol: Insight 46 – a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development – phases 2 and 3

Author

Murray-Smith, Heidi, Barker, Suzie, Barkhof, Frederik, Barnes, Josephine, Brown, Thomas M., Captur, Gabriella, R.E.Cartlidge, Molly, Cash, David M., Coath, William, Davis, Daniel, Dickson, John C., Groves, James, Hughes, Alun D., James, Sarah-Naomi, Keshavan, Ashvini, Keuss, Sarah E., King-Robson, Josh, Lu, Kirsty, Malone, Ian B., Nicholas, Jennifer M., Rapala, Alicja, Scott, Catherine J., Street, Rebecca, Sudre, Carole H., Thomas, David L., Wong, Andrew, Wray, Selina, Zetterberg, Henrik, Chaturvedi, Nishi, Fox, Nick C., Crutch, Sebastian J., Richards, Marcus, and Schott, Jonathan M.

Published
2024
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4. Early human lung immune cell development and its role in epithelial cell fate.

Author

Barnes, Josephine, Yoshida, Masahiro, He, Peng, Worlock, Kaylee, Lindeboom, Rik, Suo, Chenqu, Pett, J, Wilbrey-Clark, Anna, Dann, Emma, Mamanova, Lira, Richardson, Laura, Polanski, Krzysztof, Pennycuick, Adam, Allen-Hyttinen, Jessica, Herczeg, Iván, Arzili, Romina, Hynds, Robert, Teixeira, Vitor, Haniffa, Muzlifah, Lim, Kyungtae, Sun, Dawei, Rawlins, Emma, Oliver, Amanda, Lyons, Paul, Marioni, John, Ruhrberg, Christiana, Tuong, Zewen, Clatworthy, Menna, Reading, James, Janes, Sam, Teichmann, Sarah, Meyer, Kerstin, and Nikolić, Marko

Subjects
Humans, Immunity, Innate, Cell Differentiation, Lung, Killer Cells, Natural, Epithelial Cells
Abstract

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.

Published
2023

5. Spatial distributions of white matter hyperintensities on brain MRI: A pooled analysis of individual participant data from 11 memory clinic cohorts

Author

Coenen, Mirthe, Biessels, Geert Jan, DeCarli, Charles, Fletcher, Evan F, Maillard, Pauline M, Initiative, Alzheimer's Disease Neuroimaging, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Boomsma, Jooske MF, Chen, Christopher PLH, Dal-Bianco, Peter, Dewenter, Anna, Duering, Marco, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Groeneveld, Onno, Hilal, Saima, Hofer, Edith, Koek, Huiberdina L, Maier, Andrea B, McCreary, Cheryl R, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande AL, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Sudre, Carole H, Steketee, Rebecca ME, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Vernooij, Meike W, Wolters, Frank J, Xin, Xu, Biesbroek, J Matthijs, and Kuijf, Hugo J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Alzheimer's Disease Related Dementias (ADRD), Cerebrovascular, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Machine Learning and Artificial Intelligence, Clinical Research, Acquired Cognitive Impairment, Vascular Cognitive Impairment/Dementia, Aging, Neurodegenerative, Networking and Information Technology R&D (NITRD), Neurosciences, Brain Disorders, Dementia, Neurological, Humans, White Matter, Brain, Magnetic Resonance Imaging, Neuroimaging, Cognitive Dysfunction, Multicenter Studies as Topic, White matter hyperintensities, Brain MRI, Distribution frequencies, Lesion location, Alzheimer's Disease Neuroimaging Initiative, Biological psychology, Clinical and health psychology
Abstract

IntroductionThe spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as "unusual", but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns.MethodsIndividual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented.ResultsWMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected.DiscussionAggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

Published
2023

6. Author Correction: Human SARS-CoV-2 challenge uncovers local and systemic response dynamics

Author

Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.

Published
2024
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8. Circulating Metabolome and White Matter Hyperintensities in Women and Men

Author

Sliz, Eeva, Shin, Jean, Ahmad, Shahzad, Williams, Dylan M, Frenzel, Stefan, Gauß, Friederike, Harris, Sarah E, Henning, Ann-Kristin, Hernandez, Maria Valdes, Hu, Yi-Han, Jiménez, Beatriz, Sargurupremraj, Muralidharan, Sudre, Carole, Wang, Ruiqi, Wittfeld, Katharina, Yang, Qiong, Wardlaw, Joanna M, Völzke, Henry, Vernooij, Meike W, Schott, Jonathan M, Richards, Marcus, Proitsi, Petroula, Nauck, Matthias, Lewis, Matthew R, Launer, Lenore, Hosten, Norbert, Grabe, Hans J, Ghanbari, Mohsen, Deary, Ian J, Cox, Simon R, Chaturvedi, Nishi, Barnes, Josephine, Rotter, Jerome I, Debette, Stephanie, Ikram, M Arfan, Fornage, Myriam, Paus, Tomas, Seshadri, Sudha, Pausova, Zdenka, and Group, for the NeuroCHARGE Working

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Prevention, Clinical Research, Aging, Aged, Brain, Diabetes Mellitus, Type 2, Female, Humans, Magnetic Resonance Imaging, Male, Metabolome, Middle Aged, White Matter, NeuroCHARGE Working Group, brain, glucuronic acid, hydroxyphenylpyruvate, lipid ratios, lipidomics, lipids, lysophosphatidylcholines, metabolomics, sphingomyelins, white matter, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundWhite matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites.MethodsWe studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment-stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance-weighted method. Associations with false discovery rate (FDR)-adjusted P values (PFDR)

Published
2022

9. Mapping interindividual dynamics of innate immune response at single-cell resolution

Author

Kumasaka, Natsuhiko, Rostom, Raghd, Huang, Ni, Polanski, Krzysztof, Meyer, Kerstin B., Patel, Sharad, Boyd, Rachel, Gomez, Celine, Barnett, Sam N., Panousis, Nikolaos I., Schwartzentruber, Jeremy, Ghoussaini, Maya, Lyons, Paul A., Calero-Nieto, Fernando J., Göttgens, Berthold, Barnes, Josephine L., Worlock, Kaylee B., Yoshida, Masahiro, Nikolić, Marko Z., Stephenson, Emily, Reynolds, Gary, Haniffa, Muzlifah, Marioni, John C., Stegle, Oliver, Hagai, Tzachi, and Teichmann, Sarah A.

Published
2023
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10. Adulthood cognitive trajectories over 26 years and brain health at 70 years of age: findings from the 1946 British Birth Cohort

Author

James, Sarah-Naomi, Nicholas, Jennifer M., Lu, Kirsty, Keshavan, Ashvini, Lane, Christopher A., Parker, Thomas, Buchanan, Sarah M., Keuss, Sarah E., Murray-Smith, Heidi, Wong, Andrew, Cash, David M., Malone, Ian B., Barnes, Josephine, Sudre, Carole H., Coath, William, Modat, Marc, Ourselin, Sebastien, Crutch, Sebastian J., Kuh, Diana, Fox, Nick C., Schott, Jonathan M., and Richards, Marcus

Published
2023
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12. Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study

Author

Wagen, Aaron Z, Coath, William, Keshavan, Ashvini, James, Sarah-Naomi, Parker, Thomas D, Lane, Christopher A, Buchanan, Sarah M, Keuss, Sarah E, Storey, Mathew, Lu, Kirsty, Macdougall, Amy, Murray-Smith, Heidi, Freiberger, Tamar, Cash, David M, Malone, Ian B, Barnes, Josephine, Sudre, Carole H, Wong, Andrew, Pavisic, Ivanna M, Street, Rebecca, Crutch, Sebastian J, Escott-Price, Valentina, Leonenko, Ganna, Zetterberg, Henrik, Wellington, Henrietta, Heslegrave, Amanda, Barkhof, Frederik, Richards, Marcus, Fox, Nick C, Cole, James H, and Schott, Jonathan M

Published
2022
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14. Local and systemic responses to SARS-CoV-2 infection in children and adults

Author

Yoshida, Masahiro, Worlock, Kaylee B., Huang, Ni, Lindeboom, Rik G. H., Butler, Colin R., Kumasaka, Natsuhiko, Dominguez Conde, Cecilia, Mamanova, Lira, Bolt, Liam, Richardson, Laura, Polanski, Krzysztof, Madissoon, Elo, Barnes, Josephine L., Allen-Hyttinen, Jessica, Kilich, Eliz, Jones, Brendan C., de Wilton, Angus, Wilbrey-Clark, Anna, Sungnak, Waradon, Pett, J. Patrick, Weller, Juliane, Prigmore, Elena, Yung, Henry, Mehta, Puja, Saleh, Aarash, Saigal, Anita, Chu, Vivian, Cohen, Jonathan M., Cane, Clare, Iordanidou, Aikaterini, Shibuya, Soichi, Reuschl, Ann-Kathrin, Herczeg, Iván T., Argento, A. Christine, Wunderink, Richard G., Smith, Sean B., Poor, Taylor A., Gao, Catherine A., Dematte, Jane E., Reynolds, Gary, Haniffa, Muzlifah, Bowyer, Georgina S., Coates, Matthew, Clatworthy, Menna R., Calero-Nieto, Fernando J., Göttgens, Berthold, O’Callaghan, Christopher, Sebire, Neil J., Jolly, Clare, De Coppi, Paolo, Smith, Claire M., Misharin, Alexander V., Janes, Sam M., Teichmann, Sarah A., Nikolić, Marko Z., and Meyer, Kerstin B.

Published
2022
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16. Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial

Author

Harkness, Kirsty, Kuruvilla, Tarun, McShane, Rupert, Connelly, Peter, Duncan, Gordon, Calvert, Lucy, Lawrie, Alasdair, Sheridan, Matthew, Jackson, Eric, Udeze, Bernard, Pearson, Stephen, Langheinrich, Tobias, Wagle, Suvarna, Butchart, Joseph, Macharouthu, Ajay, Donaldson, Andrew, Neil, Wendy, Pattan, Vivek, Findlay, David, Thomas, Alan, Barber, Robert, Byrne, Andrew, Dalvi, Madhusudan, Negi, Rashi, McGuinness, Bernadette, Kehoe, Patrick Gavin, Turner, Nicholas, Howden, Beth, Jarutyte, Lina, Clegg, Shona Louise, Malone, Ian Brian, Barnes, Josephine, Nielsen, Casper, Sudre, Carole Hélène, Wilson, Aileen, Thai, Ngoc Jade, Blair, Peter Sinclair, Coulthard, Elizabeth, Lane, Janet Athene, Passmore, Peter, Taylor, Jodi, Mutsaerts, Henk-Jan, Thomas, David Lee, Fox, Nick Charles, Wilkinson, Ian, and Ben-Shlomo, Yoav

Published
2021
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18. Rates of cortical thinning in Alzheimer’s disease signature regions associate with vascular burden but not with β-amyloid status in cognitively normal adults at age 70.

Author

Keuss, Sarah E., Coath, William, Cash, David M., Barnes, Josephine, Nicholas, Jennifer M., Lane, Christopher A., Parker, Thomas D., Keshavan, Ashvini, Buchanan, Sarah M., Wagen, Aaron Z., Storey, Mathew, Harris, Matthew, Lu, Kirsty, James, Sarah-Naomi, Street, Rebecca, Malone, Ian B., Sudre, Carole H., Thomas, David L., Dickson, John C., and Barkhof, Frederik

Subjects
CEREBRAL amyloid angiopathy, CEREBRAL small vessel diseases, ALZHEIMER'S disease, SCHOLARSHIPS, RESEARCH institutes, POSITRON emission tomography
Published
2024
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21. Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2

Author

Jack, Clifford R, Barnes, Josephine, Bernstein, Matt A, Borowski, Bret J, Brewer, James, Clegg, Shona, Dale, Anders M, Carmichael, Owen, Ching, Christopher, DeCarli, Charles, Desikan, Rahul S, Fennema‐Notestine, Christine, Fjell, Anders M, Fletcher, Evan, Fox, Nick C, Gunter, Jeff, Gutman, Boris A, Holland, Dominic, Hua, Xue, Insel, Philip, Kantarci, Kejal, Killiany, Ron J, Krueger, Gunnar, Leung, Kelvin K, Mackin, Scott, Maillard, Pauline, Malone, Ian B, Mattsson, Niklas, McEvoy, Linda, Modat, Marc, Mueller, Susanne, Nosheny, Rachel, Ourselin, Sebastien, Schuff, Norbert, Senjem, Matthew L, Simonson, Alix, Thompson, Paul M, Rettmann, Dan, Vemuri, Prashanthi, Walhovd, Kristine, Zhao, Yansong, Zuk, Samantha, and Weiner, Michael

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Dementia, Alzheimer's Disease, Biomedical Imaging, Brain Disorders, Clinical Research, Clinical Trials and Supportive Activities, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurosciences, Aging, Neurodegenerative, 2.1 Biological and endogenous factors, Neurological, Alzheimer Disease, Biomarkers, Brain, Cognition Disorders, History, 20th Century, History, 21st Century, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Positron-Emission Tomography, Spin Labels, Alzheimer's disease, Alzheimer's Disease Neuroimaging Initiative, ADNI, Diffusion, MRI, Neuroimaging, Perfusion, Resting functional MRI, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionAlzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders.MethodsWe review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3.ResultsContributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials.DiscussionOver the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.

Published
2015

22. Delphi definition of the EADC‐ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance

Author

Boccardi, Marina, Bocchetta, Martina, Apostolova, Liana G, Barnes, Josephine, Bartzokis, George, Corbetta, Gabriele, DeCarli, Charles, deToledo‐Morrell, Leyla, Firbank, Michael, Ganzola, Rossana, Gerritsen, Lotte, Henneman, Wouter, Killiany, Ronald J, Malykhin, Nikolai, Pasqualetti, Patrizio, Pruessner, Jens C, Redolfi, Alberto, Robitaille, Nicolas, Soininen, Hilkka, Tolomeo, Daniele, Wang, Lei, Watson, Craig, Wolf, Henrike, Duvernoy, Henri, Duchesne, Simon, Jack, Clifford R, Frisoni, Giovanni B, and Segmentation, EADC‐ADNI Working Group on the Harmonized Protocol for Manual Hippocampal

Subjects
Neurosciences, Alzheimer Disease, Atrophy, Consensus, Delphi Technique, Hippocampus, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Internationality, Magnetic Resonance Imaging, Neuroimaging, Volumetry, Manual segmentation, Harmonization, Anatomical landmarks, Delphi procedure, Alzheimer's disease, Medial temporal Jobe, Hippocampal atrophy, Magnetic.resonance, Standard operational procedures, Enrichment, MCI, Reliability, EADC-ADNI Working Group on the Harmonized Protocol for Manual Hippocampal Segmentation, Magnetic resonance, Medial temporal lobe, Clinical Sciences, Geriatrics
Abstract

BackgroundThis study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation.MethodsThe panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests.ResultsAgreement was significant on the inclusion of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of the body according to visible morphology (P = .0006), and on this combined set of features (P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer's disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates.DiscussionConsensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol.

Published
2015

23. The EADC‐ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Author

Frisoni, Giovanni B, Jack, Clifford R, Bocchetta, Martina, Bauer, Corinna, Frederiksen, Kristian S, Liu, Yawu, Preboske, Gregory, Swihart, Tim, Blair, Melanie, Cavedo, Enrica, Grothe, Michel J, Lanfredi, Mariangela, Martinez, Oliver, Nishikawa, Masami, Portegies, Marileen, Stoub, Travis, Ward, Chadwich, Apostolova, Liana G, Ganzola, Rossana, Wolf, Dominik, Barkhof, Frederik, Bartzokis, George, DeCarli, Charles, Csernansky, John G, deToledo‐Morrell, Leyla, Geerlings, Mirjam I, Kaye, Jeffrey, Killiany, Ronald J, Lehéricy, Stephane, Matsuda, Hiroshi, O'Brien, John, Silbert, Lisa C, Scheltens, Philip, Soininen, Hilkka, Teipel, Stefan, Waldemar, Gunhild, Fellgiebel, Andreas, Barnes, Josephine, Firbank, Michael, Gerritsen, Lotte, Henneman, Wouter, Malykhin, Nikolai, Pruessner, Jens C, Wang, Lei, Watson, Craig, Wolf, Henrike, deLeon, Mony, Pantel, Johannes, Ferrari, Clarissa, Bosco, Paolo, Pasqualetti, Patrizio, Duchesne, Simon, Duvernoy, Henri, Boccardi, Marina, Initiative, EADC‐ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging, Albert, Marilyn S, Bennet, David, Camicioli, Richard, Collins, D Louis, Dubois, Bruno, Hampel, Harald, denHeijer, Tom, Hock, Christofer, Jagust, William, Launer, Leonore, Maller, Jerome J, Mueller, Susan, Sachdev, Perminder, Simmons, Andy, Thompson, Paul M, Visser, Peter‐Jelle, Wahlund, Lars‐Olof, Weiner, Michael W, and Winblad, Bengt

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Biomedical Imaging, Clinical Research, Aged, Alzheimer Disease, Atrophy, Female, Functional Laterality, Hippocampus, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Internet, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Organ Size, Reproducibility of Results, Hippocampal volumetry, Magnetic resonance, Alzheimer's disease, Biomarkers, Diagnostic criteria, Enrichment, Clinical trials, Validation, Harmonized protocol, Standard operating procedures, Manual segmentation, EADC-ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Volumetry and for the Alzheimer's Disease Neuroimaging Initiative, Geriatrics, Clinical sciences, Biological psychology
Abstract

BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001).ConclusionsThe HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.

Published
2015

24. Investigating the relationship between BMI across adulthood and late life brain pathologies

Author

Lane, Christopher A., Barnes, Josephine, Nicholas, Jennifer M., Baker, John W., Sudre, Carole H., Cash, David M., Parker, Thomas D., Malone, Ian B., Lu, Kirsty, James, Sarah-Naomi, Keshavan, Ashvini, Buchanan, Sarah, Keuss, Sarah, Murray-Smith, Heidi, Wong, Andrew, Gordon, Elizabeth, Coath, William, Modat, Marc, Thomas, David, Hardy, Rebecca, Richards, Marcus, Fox, Nick C., and Schott, Jonathan M.

Published
2021
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25. Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study

Author

Lane, Christopher A, Barnes, Josephine, Nicholas, Jennifer M, Sudre, Carole H, Cash, David M, Parker, Thomas D, Malone, Ian B, Lu, Kirsty, James, Sarah-Naomi, Keshavan, Ashvini, Murray-Smith, Heidi, Wong, Andrew, Buchanan, Sarah M, Keuss, Sarah E, Gordon, Elizabeth, Coath, William, Barnes, Anna, Dickson, John, Modat, Marc, Thomas, David, Crutch, Sebastian J, Hardy, Rebecca, Richards, Marcus, Fox, Nick C, and Schott, Jonathan M

Published
2019
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26. Spatial distributions of white matter hyperintensities on brain MRI: a pooled analysis of individual participant data from 11 memory clinic cohorts

Author

Coenen, Mirthe, primary, Jan Biessels, Geert, additional, DeCarli, Charles, additional, Fletcher, Evan F., additional, Maillard, Pauline M., additional, Barkhof, Frederik, additional, Barnes, Josephine, additional, Benke, Thomas, additional, Boomsma, Jooske M.F., additional, P.L.H. Chen, Christopher, additional, Dal-Bianco, Peter, additional, Dewenter, Anna, additional, Duering, Marco, additional, Enzinger, Christian, additional, Ewers, Michael, additional, Exalto, Lieza G., additional, Franzmeier, Nicolai, additional, Groeneveld, Onno, additional, Hilal, Saima, additional, Hofer, Edith, additional, Koek, Huiberdina L., additional, Maier, Andrea B., additional, McCreary, Cheryl R., additional, Papma, Janne M., additional, Paterson, Ross W., additional, Pijnenburg, Yolande A.L., additional, Rubinski, Anna, additional, Schmidt, Reinhold, additional, Schott, Jonathan M., additional, Slattery, Catherine F., additional, Smith, Eric E., additional, Sudre, Carole H., additional, Steketee, Rebecca M.E., additional, van den Berg, Esther, additional, van der Flier, Wiesje M., additional, Venketasubramanian, Narayanaswamy, additional, Vernooij, Meike W., additional, Wolters, Frank J., additional, Xin, Xu, additional, Matthijs Biesbroek, J., additional, and Kuijf, Hugo J., additional

Published
2023
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28. MRI-based measures in Alzheimer's disease and related disorders : regions of interest and automated techniques

Author

Barnes, Josephine

Subjects
616.8
Abstract

This thesis investigates the use of manual measures of brain structure delineation on MR scans in order to assess atrophy in dementia. It further investigates the automation of atrophy measures. A new protocol for outlining the cingulate is described and was applied to groups of Alzheimer's disease (AD) and control subjects. The application of existing hippocampal and amygdala protocols to a group of pathologically-confirmed AD, frontotemporal lobar degeneration (FTLD) and controls is detailed. This analysis shows cross-sectional measurements were useful subject-group discriminators and that patterns of atrophy within and between structures may distinguish diseases. Manual delineation of regions (cingulate and hippocampus) was extended to longitudinal studies to establish atrophy rates in groups of AD, FTLD and controls. The cingulate was shown to be at least as affected as the hippocampus by disease. Hippocampal atrophy rates from inter-scan intervals of six months were compared with measurements in the same subjects of one-year intervals. Results from studies combining cross-sectional and longitudinal hippocampal data are described. These assess the asymmetry of the structure and investigate the pre-symptomatic decrease in volume in familial AD subjects. Semi-automated techniques were performed which utilise registration of serial hippocampi to assess change longitudinally. Results show the semi-automated techniques to be reliable and consistent with manual measures. These techniques were then applied to scans from a multi-centre clinical trial and again consistency with manual measures was assessed. The generation of fully-automated template-based hippocampal segmentations is described. The approximate regions generated from the template were used to quantify the boundary shift integral and the resultant atrophy rates were compared with manual rates revealing automated measures to be consistent with manual measures. These results are put within the context of other similar studies by performing a meta analysis of hippocampal atrophy rates. Implications for diagnosis and monitoring disease progression are discussed.

Published
2007

29. Assessment of Microvascular Disease in Heart and Brain by MRI: Application in Heart Failure with Preserved Ejection Fraction and Cerebral Small Vessel Disease

Author

Bennett, Jonathan, primary, van Dinther, Maud, additional, Voorter, Paulien, additional, Backes, Walter, additional, Barnes, Josephine, additional, Barkhof, Frederick, additional, Captur, Gabriella, additional, Hughes, Alun D., additional, Sudre, Carole, additional, and Treibel, Thomas A., additional

Published
2023
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31. Human SARS-CoV-2 challenge resolves local and systemic response dynamics

Author

Lindeboom, Rik G H, primary, Worlock, Kaylee B, additional, Dratva, Lisa M, additional, Yoshida, Masahiro, additional, Scobie, David, additional, Wagstaffe, Helen R, additional, Richardson, Laura, additional, Wilbrey-Clark, Anna L, additional, Barnes, Josephine L, additional, Polanski, Krzysztof, additional, Allen-Hyttinen, Jessica, additional, Mehta, Puja, additional, Sumanaweera, Dinithi, additional, Boccacino, Jacqueline M, additional, Sungnak, Waradon, additional, Huang, Ni, additional, Mamanova, Lira, additional, Kapuge, Rakeshlal, additional, Bolt, Liam, additional, Prigmore, Elena, additional, Killingley, Ben, additional, Kalinova, Mariya, additional, Mayer, Maria, additional, Boyers, Alison, additional, Mann, Alex, additional, Teixeira, Vitor H, additional, Janes, Sam M, additional, Chambers, Rachel C, additional, Haniffa, Muzlifah, additional, Catchpole, Andrew, additional, Heyderman, Robert S, additional, Noursadeghi, Mahdad, additional, Chain, Benny, additional, Mayer, Andreas, additional, Meyer, Kerstin B, additional, Chiu, Christopher, additional, Nikolić, Marko Z, additional, and Teichmann, Sarah A, additional

Published
2023
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32. Strategic white matter hyperintensity locations for cognitive impairment:A multicenter lesion-symptom mapping study in 3525 memory clinic patients

Author

Coenen, Mirthe, Kuijf, Hugo J, Huenges Wajer, Irene M C, Duering, Marco, Wolters, Frank J, Fletcher, Evan F, Maillard, Pauline M, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Boomsma, Jooske M F, Chen, Christopher P L H, Dal-Bianco, Peter, Dewenter, Anna, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Groeneveld, Onno, Hilal, Saima, Hofer, Edith, Koek, Dineke L, Maier, Andrea B, McCreary, Cheryl R, Padilla, Catarina S, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande A L, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Steketee, Rebecca M E, Sudre, Carole H, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Vernooij, Meike W, Xin, Xu, DeCarli, Charles, Biessels, Geert Jan, Biesbroek, J Matthijs, Coenen, Mirthe, Kuijf, Hugo J, Huenges Wajer, Irene M C, Duering, Marco, Wolters, Frank J, Fletcher, Evan F, Maillard, Pauline M, Barkhof, Frederik, Barnes, Josephine, Benke, Thomas, Boomsma, Jooske M F, Chen, Christopher P L H, Dal-Bianco, Peter, Dewenter, Anna, Enzinger, Christian, Ewers, Michael, Exalto, Lieza G, Franzmeier, Nicolai, Groeneveld, Onno, Hilal, Saima, Hofer, Edith, Koek, Dineke L, Maier, Andrea B, McCreary, Cheryl R, Padilla, Catarina S, Papma, Janne M, Paterson, Ross W, Pijnenburg, Yolande A L, Rubinski, Anna, Schmidt, Reinhold, Schott, Jonathan M, Slattery, Catherine F, Smith, Eric E, Steketee, Rebecca M E, Sudre, Carole H, van den Berg, Esther, van der Flier, Wiesje M, Venketasubramanian, Narayanaswamy, Vernooij, Meike W, Xin, Xu, DeCarli, Charles, Biessels, Geert Jan, and Biesbroek, J Matthijs

Abstract

INTRODUCTION: Impact of white matter hyperintensities (WMH) on cognition likely depends on lesion location, but a comprehensive map of strategic locations is lacking. We aimed to identify these locations in a large multicenter study.METHODS: Individual patient data (n = 3525) from 11 memory clinic cohorts were harmonized. We determined the association of WMH location with attention and executive functioning, information processing speed, language, and verbal memory performance using voxel-based and region of interest tract-based analyses.RESULTS: WMH in the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus were significantly related to domain-specific impairment, independent of total WMH volume and atrophy. A strategic WMH score based on these tracts inversely correlated with performance in all domains.DISCUSSION: The data show that the impact of WMH on cognition is location-dependent, primarily involving four strategic white matter tracts. Evaluation of WMH location may support diagnosing vascular cognitive impairment.HIGHLIGHTS: We analyzed white matter hyperintensities (WMH) in 3525 memory clinic patients from 11 cohorts The impact of WMH on cognition depends on location We identified four strategic white matter tracts A single strategic WMH score was derived from these four strategic tracts The strategic WMH score was an independent determinant of four cognitive domains.

Published
2023

33. First presentation with neuropsychiatric symptoms in autosomal dominant Alzheimer's disease: The Dominantly Inherited Alzheimer's Network Study

Author

O'Connor, Antoinette, Rice, Helen, Barnes, Josephine, Ryan, Natalie S., Liu, Kathy Y., Allegri, Ricardo Francisco, Berman, Sarah, Ringman, John M., Cruchaga, Carlos, Farlow, Martin R., Hassenstab, Jason, Lee, Jae-Hong, Perrin, Richard J., Xiong, Chengjie, Gordon, Brian, Levey, Allan I., Goate, Alison, Graff-Radford, Neil, Levin, Johannes, Jucker, Mathias, Benzinger, Tammie, McDade, Eric, Mori, Hiroshi, Noble, James M., Schofield, Peter R., Martins, Ralph N., Salloway, Stephen, Chhatwal, Jasmeer, Morris, John C., Bateman, Randall, Howard, Rob, Reeves, Suzanne, Fox, Nick C., O'Connor, Antoinette, Rice, Helen, Barnes, Josephine, Ryan, Natalie S., Liu, Kathy Y., Allegri, Ricardo Francisco, Berman, Sarah, Ringman, John M., Cruchaga, Carlos, Farlow, Martin R., Hassenstab, Jason, Lee, Jae-Hong, Perrin, Richard J., Xiong, Chengjie, Gordon, Brian, Levey, Allan I., Goate, Alison, Graff-Radford, Neil, Levin, Johannes, Jucker, Mathias, Benzinger, Tammie, McDade, Eric, Mori, Hiroshi, Noble, James M., Schofield, Peter R., Martins, Ralph N., Salloway, Stephen, Chhatwal, Jasmeer, Morris, John C., Bateman, Randall, Howard, Rob, Reeves, Suzanne, and Fox, Nick C.

Abstract

Behavioural changes and neuropsychiatric symptoms (NPS) commonly occur in Alzheimer’s disease (AD) but may not be recognised as AD-related when they are the presenting feature. NPS are important as they are associated with greater functional impairment, poorer quality of life, accelerated cognitive decline and worsened caregiver burden.1 Autosomal dominant AD (ADAD), although < 1% of total AD cases, provides a valuable opportunity to study the clinical heterogeneity of AD. The young age at onset reduces the prevalence of age-related comorbid pathologies and the near 100% penetrance of pathogenic mutations reduces the likelihood of misdiagnosis.2 Anxiety and depression commonly occur in ADAD family members, with increased levels of depression having been found among predementia female mutation carriers.3 Subsequent studies, however, have shown that anxiety and/or depression are common regardless of mutation status, occurring in almost one in three at-risk individuals, with one study reporting a higher rate of depression in non-carriers (17%) than asymptomatic carriers (5%).4 5 Despite the high frequency of NPS in ADAD families, relatively little is known about the proportion of ADAD cases who present with predominantly behavioural symptoms. Our aims were to assess the first reported clinical change in symptomatic ADAD, to compare presentations across genotypes, and to compare cognitive performance between behavioural and cognitive-led presentations.

Published
2023

34. Predicting Cognitive Decline in Older Adults Using Baseline Metrics of AD Pathologies, Cerebrovascular Disease, and Neurodegeneration

Author

Neurologen, Brain, Circulatory Health, Prosser, Lloyd, MacDougall, Amy, Sudre, Carole H., Manning, Emily N., Malone, Ian B., Walsh, Phoebe, Goodkin, Olivia, Pemberton, Hugh, Barkhof, Frederik, Biessels, Geert Jan, Cash, David M., Barnes, Josephine, Neurologen, Brain, Circulatory Health, Prosser, Lloyd, MacDougall, Amy, Sudre, Carole H., Manning, Emily N., Malone, Ian B., Walsh, Phoebe, Goodkin, Olivia, Pemberton, Hugh, Barkhof, Frederik, Biessels, Geert Jan, Cash, David M., and Barnes, Josephine

Published
2023

35. Bayesian Model Selection for Pathological Data

Author

Sudre, Carole H., Cardoso, Manuel Jorge, Bouvy, Willem, Biessels, Geert Jan, Barnes, Josephine, Ourselin, Sébastien, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Kobsa, Alfred, Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Golland, Polina, editor, Hata, Nobuhiko, editor, Barillot, Christian, editor, Hornegger, Joachim, editor, and Howe, Robert, editor

Published
2014
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36. Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds

Author

James, Sarah-Naomi, primary, Manning, Emily N, additional, Storey, Mathew, additional, Nicholas, Jennifer M, additional, Coath, William, additional, Keuss, Sarah E, additional, Cash, David M, additional, Lane, Christopher A, additional, Parker, Thomas, additional, Keshavan, Ashvini, additional, Buchanan, Sarah M, additional, Wagen, Aaron, additional, Harris, Mathew, additional, Malone, Ian, additional, Lu, Kirsty, additional, Needham, Louisa P, additional, Street, Rebecca, additional, Thomas, David, additional, Dickson, John, additional, Murray-Smith, Heidi, additional, Wong, Andrew, additional, Freiberger, Tamar, additional, Crutch, Sebastian J, additional, Fox, Nick C, additional, Richards, Marcus, additional, Barkhof, Frederik, additional, Sudre, Carole H, additional, Barnes, Josephine, additional, and Schott, Jonathan M, additional

Published
2023
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38. The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity

Author

Albert, Marilyn S., Bennet, David, Camicioli, Richard, Collins, D. Louis, Dubois, Bruno, Hampel, Harald, denHeijer, Tom, Hock, Christofer, Jagust, William, Launer, Leonore, Maller, Jerome J., Mueller, Susan, Sachdev, Perminder, Simmons, Andy, Thompson, Paul M., Visser, Peter-Jelle, Wahlund, Lars-Olof, Weiner, Michael W., Winblad, Bengt, Frisoni, Giovanni B., Jack, Clifford R., Jr., Bocchetta, Martina, Bauer, Corinna, Frederiksen, Kristian S., Liu, Yawu, Preboske, Gregory, Swihart, Tim, Blair, Melanie, Cavedo, Enrica, Grothe, Michel J., Lanfredi, Mariangela, Martinez, Oliver, Nishikawa, Masami, Portegies, Marileen, Stoub, Travis, Ward, Chadwich, Apostolova, Liana G., Ganzola, Rossana, Wolf, Dominik, Barkhof, Frederik, Bartzokis, George, DeCarli, Charles, Csernansky, John G., deToledo-Morrell, Leyla, Geerlings, Mirjam I., Kaye, Jeffrey, Killiany, Ronald J., Lehéricy, Stephane, Matsuda, Hiroshi, O'Brien, John, Silbert, Lisa C., Scheltens, Philip, Soininen, Hilkka, Teipel, Stefan, Waldemar, Gunhild, Fellgiebel, Andreas, Barnes, Josephine, Firbank, Michael, Gerritsen, Lotte, Henneman, Wouter, Malykhin, Nikolai, Pruessner, Jens C., Wang, Lei, Watson, Craig, Wolf, Henrike, deLeon, Mony, Pantel, Johannes, Ferrari, Clarissa, Bosco, Paolo, Pasqualetti, Patrizio, Duchesne, Simon, Duvernoy, Henri, and Boccardi, Marina

Published
2015
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41. Local and systemic responses to SARS-CoV-2 infection in children and adults

Author

Yoshida, Masahiro, Worlock, Kaylee B., Huang, Ni, Lindeboom, Rik G. H., Butler, Colin R., Kumasaka, Natsuhiko, Dominguez Conde, Cecilia, Mamanova, Lira, Bolt, Liam, Richardson, Laura, Polanski, Krzysztof, Madissoon, Elo, Barnes, Josephine L., Allen-Hyttinen, Jessica, Kilich, Eliz, Jones, Brendan C., de Wilton, Angus, Wilbrey-Clark, Anna, Sungnak, Waradon, Pett, J. Patrick, Weller, Juliane, Prigmore, Elena, Yung, Henry, Mehta, Puja, Saleh, Aarash, Saigal, Anita, Chu, Vivian, Cohen, Jonathan M., Cane, Clare, Iordanidou, Aikaterini, Shibuya, Soichi, Reuschl, Ann-Kathrin, Herczeg, Iván T., Argento, A. Christine, Wunderink, Richard G., Smith, Sean B., Poor, Taylor A., Gao, Catherine A., Dematte, Jane E., Budinger, G. R. Scott, Donnelly, Helen K., Markov, Nikolay S., Lu, Ziyan, Reynolds, Gary, Haniffa, Muzlifah, Bowyer, Georgina S., Coates, Matthew, Clatworthy, Menna R., Calero-Nieto, Fernando J., Göttgens, Berthold, O’Callaghan, Christopher, Sebire, Neil J., Jolly, Clare, De Coppi, Paolo, Smith, Claire M., Misharin, Alexander V., Janes, Sam M., Teichmann, Sarah A., Nikolić, Marko Z., and Meyer, Kerstin B.

Subjects
Multidisciplinary Sciences, Science & Technology, Multidisciplinary, Science & Technology - Other Topics, COVID-19, CELL
Abstract

It is not fully understood why COVID-19 is typically milder in children1–3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Published
2021
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42. An Event-Based Disease Progression Model and Its Application to Familial Alzheimer’s Disease

Author

Fonteijn, Hubert M., Clarkson, Matthew J., Modat, Marc, Barnes, Josephine, Lehmann, Manja, Ourselin, Sebastien, Fox, Nick C., Alexander, Daniel C., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Székely, Gábor, editor, and Hahn, Horst K., editor

Published
2011
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43. First presentation with neuropsychiatric symptoms in autosomal dominant Alzheimer’s disease: the Dominantly Inherited Alzheimer’s Network Study

Author

O'Connor, Antoinette, primary, Rice, Helen, additional, Barnes, Josephine, additional, Ryan, Natalie S, additional, Liu, Kathy Y, additional, Allegri, Ricardo Francisco, additional, Berman, Sarah, additional, Ringman, John M, additional, Cruchaga, Carlos, additional, Farlow, Martin R, additional, Hassenstab, Jason, additional, Lee, Jae-Hong, additional, Perrin, Richard J, additional, Xiong, Chengjie, additional, Gordon, Brian, additional, Levey, Allan I, additional, Goate, Alison, additional, Graff-Radford, Neil, additional, Levin, Johannes, additional, Jucker, Mathias, additional, Benzinger, Tammie, additional, McDade, Eric, additional, Mori, Hiroshi, additional, Noble, James M, additional, Schofield, Peter R, additional, Martins, Ralph N, additional, Salloway, Stephen, additional, Chhatwal, Jasmeer, additional, Morris, John C, additional, Bateman, Randall, additional, Howard, Rob, additional, Reeves, Suzanne, additional, and Fox, Nick C, additional

Published
2022
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44. Early human lung immune cell development and its role in epithelial cell fate

Author

Barnes, Josephine L., primary, He, Peng, additional, Yoshida, Masahiro, additional, Worlock, Kaylee B., additional, Lindeboom, Rik G.H., additional, Suo, Chenqu, additional, Pett, J. Patrick, additional, Wilbrey-Clark, Anna, additional, Dann, Emma, additional, Mamanova, Lira, additional, Richardson, Laura, additional, Oliver, Amanda J., additional, Pennycuick, Adam, additional, Allen-Hyttinen, Jessica, additional, Herczeg, Iván T., additional, Hynds, Robert E., additional, Teixeira, Vitor H., additional, Haniffa, Muzlifah, additional, Lim, Kyungtae, additional, Sun, Dawei, additional, Rawlins, Emma L., additional, Polanski, Krzysztof, additional, Lyons, Paul A., additional, Marioni, John C., additional, Tuong, Zewen Kelvin, additional, Clatworthy, Menna R., additional, Reading, James L., additional, Janes, Sam M., additional, Teichmann, Sarah A., additional, Meyer, Kerstin B., additional, and Nikolić, Marko Z., additional

Published
2022
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45. R47H TREM2 variant increases risk of typical early-onset Alzheimer's disease but not of prion or frontotemporal dementia

Author

Slattery, Catherine F., Beck, Jonathan A., Harper, Lorna, Adamson, Gary, Abdi, Zeinab, Uphill, James, Campbell, Tracy, Druyeh, Ron, Mahoney, Colin J., Rohrer, Jonathan D., Kenny, Janna, Lowe, Jessica, Leung, Kelvin K., Barnes, Josephine, Clegg, Shona L., Blair, Melanie, Nicholas, Jennifer M., Guerreiro, Rita J., Rowe, James B., Ponto, Claudia, Zerr, Inga, Kretzschmar, Hans, Gambetti, Pierluigi, Crutch, Sebastian J., Warren, Jason D., Rossor, Martin N., Fox, Nick C., Collinge, John, Schott, Jonathan M., and Mead, Simon

Published
2014
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46. Increasing Power to Predict Mild Cognitive Impairment Conversion to Alzheimer’s Disease Using Hippocampal Atrophy Rate and Statistical Shape Models

Author

Leung, Kelvin K., Shen, Kai-Kai, Barnes, Josephine, Ridgway, Gerard R., Clarkson, Matthew J., Fripp, Jurgen, Salvado, Olivier, Meriaudeau, Fabrice, Fox, Nick C., Bourgeat, Pierrick, Ourselin, Sébastien, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Jiang, Tianzi, editor, Navab, Nassir, editor, Pluim, Josien P. W., editor, and Viergever, Max A., editor

Published
2010
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47. Nonlinear Elastic Spline Registration: Evaluation with Longitudinal Huntington’s Disease Data

Author

Modat, Marc, Taylor, Zeike A., Ridgway, Gerard R., Barnes, Josephine, Wild, Edward J., Hawkes, David J., Fox, Nick C., Ourselin, Sébastien, Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Fischer, Bernd, editor, Dawant, Benoît M., editor, and Lorenz, Cristian, editor

Published
2010
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48. Single-cell multi-omics analysis of the immune response in COVID-19

Author

Stephenson, Emily, Reynolds, Gary, Botting, Rachel A., Calero-Nieto, Fernando J., Morgan, Michael D., Tuong, Zewen Kelvin, Bach, Karsten, Sungnak, Waradon, Worlock, Kaylee B., Yoshida, Masahiro, Kumasaka, Natsuhiko, Kania, Katarzyna, Engelbert, Justin, Olabi, Bayanne, Spegarova, Jarmila Stremenova, Wilson, Nicola K., Mende, Nicole, Jardine, Laura, Gardner, Louis C. S., Goh, Issac, Horsfall, Dave, McGrath, Jim, Webb, Simone, Mather, Michael W., Lindeboom, Rik G. H., Dann, Emma, Huang, Ni, Polanski, Krzysztof, Prigmore, Elena, Gothe, Florian, Scott, Jonathan, Payne, Rebecca P., Baker, Kenneth F., Hanrath, Aidan T., Schim van der Loeff, Ina C. D., Barr, Andrew S., Sanchez-Gonzalez, Amada, Bergamaschi, Laura, Mescia, Federica, Barnes, Josephine L., Kilich, Eliz, de Wilton, Angus, Saigal, Anita, Saleh, Aarash, Janes, Sam M., Smith, Claire M., Gopee, Nusayhah, Wilson, Caroline, Coupland, Paul, Coxhead, Jonathan M., Kiselev, Vladimir Yu, van Dongen, Stijn, Bacardit, Jaume, King, Hamish W., Rostron, Anthony J., Simpson, A. John, Hambleton, Sophie, Laurenti, Elisa, Lyons, Paul A., Meyer, Kerstin B., Nikolić, Marko Z., Duncan, Christopher J. A., Smith, Kenneth G. C., Teichmann, Sarah A., Clatworthy, Menna R., Marioni, John C., Göttgens, Berthold, and Haniffa, Muzlifah

Subjects
Proteome, COVID-19, Cross-Sectional Studies, Humans, Monocytes, Receptors, Antigen, B-Cell, Receptors, Antigen, T-Cell, SARS-CoV-2, Single-Cell Analysis, T-Lymphocytes, Transcriptome, CD34, Biology, Peripheral blood mononuclear cell, Article, General Biochemistry, Genetics and Molecular Biology, Immune system, Antigen, Receptors, Platelet activation, Progenitor cell, B-Cell, RNA sequencing, General Medicine, T-Cell, Haematopoiesis, Viral infection, Immunology, Infection, CD8
Abstract

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy., Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Published
2021
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49. Straight and Divergent Pathways to Cognitive State: Seven Decades of Follow-Up in the British 1946 Birth Cohort

Author

Richards, Marcus, primary, James, Sarah N., additional, Lu, Kirsty, additional, Livingston, Gill, additional, Schott, Jonathan M., additional, Lane, Christopher A., additional, Barnes, Josephine, additional, Parker, Thomas D., additional, Sudre, Carole H., additional, Cash, David M., additional, Coath, William, additional, Fox, Nicholas, additional, and Davis, Daniel H.J., additional

Published
2022
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50. Accelerated vascular aging: Ethnic differences in basilar artery length and diameter, and its association with cardiovascular risk factors and cerebral small vessel disease

Author

Sudre, Carole H., primary, Moriconi, Stefano, additional, Rehwald, Rafael, additional, Smith, Lorna, additional, Tillin, Therese, additional, Barnes, Josephine, additional, Atkinson, David, additional, Ourselin, Sébastien, additional, Chaturvedi, Nish, additional, Hughes, Alun D., additional, Jäger, H. Rolf, additional, and Cardoso, M. Jorge, additional

Published
2022
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