Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.
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2023-05
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Abstract
Background and objectives
Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke 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 vs poor outcomes.Methods
We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the 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 3-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 vs poor outcomes in patients with matched lesion damage.Results
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 to -0.15, p < 0.001) and across multiple domains of function (β = -0.14; 95% CI -0.22 to -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 (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004).Discussion
We provide evidence that younger brain age is associated with superior poststroke 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 poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.Type
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Liew, Sook-Lei, Nicolas Schweighofer, James H Cole, Artemis Zavaliangos-Petropulu, Bethany P Tavenner, Laura KM Han, Tim Hahn, Lianne Schmaal, et al. (2023). Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke. Neurology, 100(20). pp. e2103–e2113. 10.1212/wnl.0000000000207219 Retrieved from https://hdl.handle.net/10161/34010.
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Scholars@Duke
Charalambos Costas Charalambous
Since October 2023, I have been a Medical Instructor in the Division of Stroke and Vascular Neurology, Department of Neurology at the Duke University School of Medicine. I hold a BS and MS in Kinesiology from the California State University Northridge, an MS in Biokinesiology from the University of Southern California, and a PhD in Health and Rehabilitation Sciences from the Medical University of South Carolina. Before my current academic position, I completed three postdoctoral fellowships at the University of Delaware in Movement Science and Behavioral Neuroscience (1/2016-1/2018), the New York University Grossman School of Medicine in TMS Neurophysiology and Post-Stroke Motor Recovery (2/2018-12/20019), and University of Nicosia Medical School in Neuroscience (12/2019-9/2023).
I am a motor neuroscientist/biomechanist dedicated to uncovering the neural and biomechanical principles that govern human motor control, particularly following neurological injury. My overarching research mission is to elucidate how the plasticity of descending motor pathways contributes to the neuromechanical control of movement (e.g., walking), and to determine how this plasticity can be leveraged to promote recovery of motor function after neurological damage. Through my basic clinical research with humans, I aim to advance fundamental understanding of how the central nervous system coordinates human movement and to translate this knowledge into mechanism-driven rehabilitation strategies that restore mobility, independence, and quality of life in individuals with neurological conditions. My expertise spans human movement biomechanics, motor neuroscience, locomotor control, non-invasive brain stimulation, neural oscillations, motor behavior, and neural plasticity and recovery, an integrative framework that bridges motor neuroscience, biomechanics, and neurorehabilitation science.
Wuwei Feng
Wayne Feng is the Chief of Division of Stroke & Vascular Neurology, Medical Director of Duke Comprehensive Stroke Center, and Tenured Profess of Neurology and Biomedical Engineering at Duke University School of Medicine. Dr. Feng is a board-certified vascular neurologist as well as a physician scientist. His research portfolios include developing imaging biomarker for post-stroke motor outcomes prediction, and use of non-invasive brain stimulation tools, such as, transcranial direct current stimulation (tDCS), vagus nerve stimulation, low intensity focused ultrasound and transcranial light stimulation to enhance post-stroke recovery. His research has been actively funded by the National Institute of Health (NIH), the American Heart Association/American Stroke Association (AHA/ASA) and other various sources. He is currently leading an NIH funded 8.9 million U01 12-center, phase II study called TRANSPORT 2 (TRANScranial direct current stimulation for POst-stroke motor Recovery – a phase II sTudy) – on the NINDS funded stroke trial network.
Dr. Feng has published over 150 peer reviewed manuscripts (H index of 36), including two manuscripts featured on the cover page of brain stimulation journal, and one manuscript featured on Journal of Neuroscience. He co-edited - “Cerebral Venous System in Acute and Chronic Brain Injuries” book. He served as the associate editor for Translational Stroke Research from 2019 to 2021(IF=7.0). Dr. Feng received several prestigious awards for his research work in stroke and stroke recovery including the FIRST “Rehabilitation Award” from the American Heart Association/American Stroke Association in 2015, “Franz Gerstenbrand Award” from World Federation of Neurorehabilitation (WFNR) in 2016, Arthur Guyton New Investigator Award, Consortium for Southeastern Hypertension Control (COSEHC) in 2016 and “Clinical Investigator Award” from the Society of Chinese American Physician Entrepreneur (SCAPE). Currently, he is the Section Chair of Neural Repair & Rehabilitation, the American Academy of Neurology. He leads the global mentoring program for the WFNR.
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