Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/32653
Title: Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.
Austin Authors: Liew, Sook-Lei;Schweighofer, Nicolas;Cole, James H;Zavaliangos-Petropulu, Artemis;Lo, Bethany P;Han, Laura K M;Hahn, Tim;Schmaal, Lianne;Donnelly, Miranda R;Jeong, Jessica N;Wang, Zhizhuo;Abdullah, Aisha;Kim, Jun H;Hutton, Alexandre M;Barisano, Giuseppe;Borich, Michael R;Boyd, Lara A;Brodtmann, Amy ;Buetefisch, Cathrin M;Byblow, Winston D;Cassidy, Jessica M;Charalambous, Charalambos C;Ciullo, Valentina;Conforto, Adriana Bastos;Dacosta-Aguayo, Rosalia;DiCarlo, Julie A;Domin, Martin;Dula, Adrienne N;Egorova-Brumley, Natalia;Feng, Wuwei;Geranmayeh, Fatemeh;Gregory, Chris M;Hanlon, Colleen A;Hayward, Kathryn S ;Holguin, Jess A;Hordacre, Brenton;Jahanshad, Neda;Kautz, Steven A;Khlif, Mohamed Salah;Kim, Hosung;Kuceyeski, Amy;Lin, David J;Liu, Jingchun;Lotze, Martin;MacIntosh, Bradley J;Margetis, John L;Mataro, Maria;Mohamed, Feroze B;Olafson, Emily R;Park, Gilsoon;Piras, Fabrizio;Revill, Kate P;Roberts, Pamela;Robertson, Andrew D;Sanossian, Nerses;Schambra, Heidi M;Seo, Na Jin;Soekadar, Surjo R;Spalletta, Gianfranco;Stinear, Cathy M;Taga, Myriam;Tang, Wai Kwong;Thielman, Greg T;Vecchio, Daniela;Ward, Nick S;Westlye, Lars T;Winstein, Carolee J;Wittenberg, George F;Wolf, Steven L;Wong, Kristin A;Yu, Chunshui;Cramer, Steven C;Thompson, Paul M
Affiliation: Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA;Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, 90089, USA.
Division of Biokinesiology and Physical Therapy, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.
Centre for Medical Image Computing, Department of Computer Science, University College London, London, WC1V 6LJ, UK.;Dementia Research Centre, Queen Square Institute of Neurology, University College London, London, UK.
Brain Mapping Center, Department of Neurology, Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, 90089, USA.
Centre for Youth Mental Health, The University of Melbourne, Parkville, Victoria, 3052, Australia
Institute for Translational Psychiatry, University of Münster, Münster, 48149, Germany.
The Florey Institute of Neuroscience and Mental Health
Laboratory of Neuro Imaging, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90066, USA.
Division of Physical Therapy, Department of Rehabilitation Medicine, Emory School of Medicine, Atlanta, GA, 30322, USA.
Department of Physical Therapy and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Eastern Cognitive Disorders Clinic, Melbourne, Victoria, 3128, Australia.;Royal Melbourne Hospital, Melbourne, Victoria, 3050, Australia.
Department of Neurology, Emory University, Atlanta, GA, 30322, USA.
Centre for Brain Research and Department of Exercise Sciences, University of Auckland, Auckland, 1142, New Zealand.
Department of Allied Health Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, 2414, Cyprus.;Center for Neuroscience and Integrative Brain Research (CENIBRE), University of Nicosia Medical School, Nicosia, 2414, Cyprus.
Hospital das Clínicas, São Paulo University, São Paulo, 05403-000, Brazil.;Hospital Israelita Albert Einstein, São Paulo, 05652-900, Brazil.
Department of Psychiatry and Clinical Psychobiology, Universitat de Barcelona, Barcelona, Barcelona, 8035, Spain.
Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Functional Imaging Unit, Diagnostic and Neuroradiology, Universitymedicine Greifswald, Greifswald, 17475, Germany.
Department of Neurology, Dell Medical School at The University of Texas Austin, Austin, TX, 78732, USA.
Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, 3052, Australia.
Department of Neurology, Duke University School of Medicine, Durham, NC, 27710, USA.
Clinical Language and Cognition (CLC) Lab, Department of Brain Sciences, Imperial College London, London, W12 0NN, UK.
Department of Health Sciences & Research, Medical University of South Carolina, Charleston, SC, 29425, USA.
Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC, 27157, USA.
Innovation, Implementation and Clinical Translation (IIMPACT) in Health, Allied Health and Human Performance, University of South Australia, Adelaide, South Australia, 5000, Australia.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90292, USA.
Department of Health Sciences & Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, 29425, USA.;Ralph H Johnson VA Medical Center, Charleston, SC, 29401, USA.
Department of Radiology, Weill Cornell Medicine, New York, NY, 10065, USA.
Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
Functional Imaging Unit, Diagnostic Radiology and Neuroradiology, Universitymedicine Greifswald, Greifswald, 17475, Germany.
Hurvitz Brain Sciences Program, Centre for Brain Resilience & Recovery, Sunnybrook Research Institute, Toronto, Ontario, M4N3M5, Canada.;Computational Radiology Artificial Intelligence unit, Oslo University Hospital, Oslo, 372, Norway.
Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, 8035, Spain.;Institut de Neurociències, University of Barcelona, Barcelona, Spain.;Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, Esplugues de Llobregat, Spain.
Jefferson Integrated MRI Center, Department of Radiology, Thomas Jefferson University, Philadelphia, PA, 19104, USA.
Department of Radiology, Weill Cornell Medicine, New York, NY, 10065, USA.
Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, 149, Italy.
Facility for Education and Research in Neuroscience, Emory University, Atlanta, GA, 30322, USA.
Cedars-Sinai, Los Angeles, CA, 90048, USA.;California Rehabilitation Institute, Los Angeles, CA, 90067, USA.
Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, M4N 3M5, Canada.;Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada.
Department of Neurology, Keck School of Medicine, Los Angeles, CA, 91030, USA.
Department of Neurology, NYU Langone, New York, NY, 10017, USA.
Department of Rehabilitation Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA.;Department of Health Sciences and Research, Medical University of South Carolina, Charleston, SC, 29425, USA.;Ralph H. Johnson VA Medical Center, Charleston, SC, 29425, USA.
Department of Psychiatry and Neurosciences, Clinical Neurotechnology Laboratory, Charité - Universitätsmedizin Berlin, Berlin, 10117, Germany.
Department of Medicine, University of Auckland, Auckland, 1142, New Zealand.
Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Department of Physical Therapy and Neuroscience, University of the Sciences, Philadelphia, PA, 19104, USA.
Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, 179, Italy.
UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Department of Psychology, University of Oslo, Oslo, 317, Norway.;Norwegian Centre for Mental Disorders Research (NORMENT), Department of Mental Health and Addiction, Oslo University Hospital, Oslo, 424, Norway.
Division of Biokinesiology and Physical Therapy, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, 90033, USA.;Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Department of Neurology & RNEL, University of Pittsburgh, Pittsburgh, PA, 15213, USA.;GRECC/HERL, VA Pittsburgh Healthcare System, Pittsburgh, PA, 15240, USA.
Department of Rehabilitation Medicine Division of Physical Therapy, Emory University School of Medicine, Atlanta, GA, 30322, USA.;Department of Medicine, Division of Geriatric Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA.;Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA.;Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Health Care System, Atlanta, GA, 30303, USA.
Department of Physical Medicine & Rehabilitation, Dell Medical School, University of Texas at Austin, Austin, TX, 78701, USA.
Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Neurology, University of California, Los Angeles, CA, 90095, USA.;California Rehabilitation Institute, Los Angeles, CA, 90067, USA.
Issue Date: 16-May-2023
Date: 2023
Publication information: Neurology 2023-05-16; 100(20)
Abstract: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. Here, we examined the impact of brain age, a measure of neurobiological aging derived from whole brain structural neuroimaging, on post-stroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good versus poor outcomes. We conducted a cross-sectional observational study using a multi-site dataset of 3D brain structural MRIs and clinical measures from ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a three-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good versus poor outcomes in patients with matched lesion damage. We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (β=0.21; 95% CI 0.04,0.38, P=0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (β=-0.28; 95% CI: -0.41,-0.15, P<0.001) and across multiple domains of function (β=-0.14; 95% CI: -0.22,-0.06, P<0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI: 3%,58%, P=0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (OR=1.04, 95% CI: 1.01,1.08, P=0.004). We provide evidence that younger brain age is associated with superior post-stroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of post-stroke outcomes compared to focal injury measures alone, opening new possibilities for potential therapeutic targets.
URI: https://ahro.austin.org.au/austinjspui/handle/1/32653
DOI: 10.1212/WNL.0000000000207219
ORCID: 0000-0001-5935-4215
0000-0003-1908-5588
0000-0001-9647-3723
0000-0002-1983-3008
0000-0001-5598-1369
0000-0001-9897-9867
0000-0002-2828-4549
0000-0001-9466-2862
0000-0001-8347-6730
0000-0003-3469-0399
0000-0002-9244-2900
0000-0001-5240-3264
0000-0002-7129-6684
0000-0003-4401-8950
0000-0002-5050-8342
0000-0001-7300-2355
0000-0001-8008-9516
0000-0001-9497-7987
0000-0002-1675-3782
0000-0002-8218-9518
0000-0001-6446-5905
0000-0003-1280-5538
0000-0002-7432-4249
0000-0001-8644-956X
0000-0001-5603-1197
0000-0002-4720-8867
Journal: Neurology
PubMed URL: 37015818
ISSN: 1526-632X
Type: Journal Article
Appears in Collections:Journal articles

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