Global brain health modulates the impact of lesion damage on post-stroke sensorimotor outcomes
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 , 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 B. , Dacosta-Aguayo Rosalia , DiCarlo Julie A. , Domin Martin , Dula Adrienne N. , Egorova-Brumley Natalia , Feng Wuwei , Geranmayeh Fatemeh , Gregory Chris M. , Hanlon Colleen A. , 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. 
Published: May 2022

Sensorimotor performance after stroke is strongly related to focal injury measures such as corticospinal tract lesion load. 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 sensorimotor outcomes. We hypothesized that stroke lesion damage would result in older brain age, which would in turn be associated with poorer sensorimotor outcomes. We also expected that brain age would mediate the impact of lesion damage on sensorimotor outcomes and that these relationships would be driven by post-stroke secondary atrophy (e.g., strongest in the ipsilesional hemisphere in chronic stroke). We further hypothesized that structural brain resilience, which we define in the context of stroke as the brain’s ability to maintain its global integrity despite focal lesion damage, would differentiate people with better versus worse outcomes.

We analyzed cross-sectional high-resolution brain MRI and outcomes data from 963 people with stroke from 38 cohorts worldwide using robust linear mixed-effects regressions to examine the relationship between sensorimotor behavior, lesion damage, and brain age. We used a mediation analysis to examine whether brain age mediates the impact of lesion damage on stroke outcomes and if associations are driven by ipsilesional measures in chronic (≥180 days) stroke. We assessed the impact of brain resilience on sensorimotor outcome using logistic regression with propensity score matching on lesion damage.

Stroke lesion damage was associated with older brain age, which in turn was associated with poorer sensorimotor outcomes. Brain age mediated the impact of corticospinal tract lesion load on sensorimotor outcomes most strongly in the ipsilesional hemisphere in chronic stroke. Greater brain resilience, as indexed by younger brain age, explained why people have better versus worse sensorimotor outcomes when lesion damage was fixed.

We present novel evidence that global brain health is associated with superior post-stroke sensorimotor outcomes and modifies the impact of focal damage. This relationship appears to be due to post-stroke secondary degeneration. Brain resilience provides insight into why some people have better outcomes after stroke, despite similar amounts of focal injury. Inclusion of imaging-based assessments of global brain health may improve prediction of post-stroke sensorimotor outcomes compared to focal injury measures alone. This investigation is important because it introduces the potential to apply novel therapeutic interventions to prevent or slow brain aging from other fields (e.g., Alzheimer’s disease) to stroke.