Related Experiment Video
Updated: Aug 9, 2025
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke
Natalia Egorova-Brumley1, Thijs Dhollander2, Wasim Khan2
1From the Melbourne School of Psychological Sciences (N.E.-B.), University of Melbourne; Dementia Theme (N.E.-B., W.K., M.S.K., D.E., A.B.), The Florey Institute of Neuroscience and Mental Health; Developmental Imaging (T.D.), Murdoch Children's Research Institute; and Cognitive Health Initiative (M.S.K., A.B.), Central Clinical School (CCS), Monash University, Melbourne, Australia. natalia.brumley@unimelb.edu.au.
Background And Objectives:
Cerebral white matter health can be estimated by MRI-derived indices of microstructure. White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition and to functional outcomes after stroke. Reduced indices of white matter microstructure have been demonstrated cross-sectionally in stroke survivors compared with stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterize white matter micro- and macrostructure over 3 years after stroke and study associations with white matter metrics and cognitive functions.
Methods:
Patients with first-ever or recurrent ischemic stroke of any etiology in any vascular territory were compared with stroke-free age- and sex-matched controls. Those diagnosed with hemorrhagic stroke, TIA, venous infarction, or significant medical comorbidities, psychiatric and neurodegenerative disorders, substance abuse, or history of dementia were excluded. Diffusion-weighted MRI data at 3, 12, and 36 months were analyzed using a longitudinal fixel-based analysis, sensitive to fiber tract-specific differences within a voxel. It was used to examine whole-brain white matter degeneration in stroke compared with control participants. We studied microstructural differences in fiber density and macrostructural changes in fiber-bundle cross-section, in relation to cognitive performance. Analyses were performed controlling for age, intracranial volume, and education (family-wise error-corrected p < 0.05, nonparametric testing over 5,000 permutations).
Results:
We included 71 participants with stroke (age 66 ± 12 years, 22 women) and 36 controls (age 69 ± 5 years, 13 women). We observed extensive white matter structural degeneration across the whole brain, particularly affecting the thalamic, cerebellar, striatal, and superior longitudinal tracts and corpus callosum. Importantly, follow-up regression analyses in 72 predefined tracts showed that the decline in fiber density and cross-section from 3 months to 3 years was associated with worse cognitive performance at 3 years after stroke, especially affecting visuospatial processing, processing speed, language, and recognition memory.
Discussion:
We conclude that white matter neurodegeneration in ipsi- and contralesional thalamic, striatal, and cerebellar tracts continues to be greater in stroke survivors compared with stroke-free controls. White matter degeneration persists even years after stroke and is associated with poststroke cognitive impairment.
Trial Registration Information:
ClinicalTrails.gov NCT02205424.
Insights
White matter degeneration continues for years after stroke, impacting cognitive functions like visuospatial processing and memory. This study tracked white matter changes over three years post-stroke.
Area of Science:
- Neuroimaging
- Neurology
- Cognitive Science
Background:
- White matter dysfunction contributes to cognitive decline in neurodegenerative disorders and stroke outcomes.
- Longitudinal white matter changes after stroke are not well understood.
- MRI-derived indices estimate cerebral white matter health.
Purpose of the Study:
- To characterize white matter micro- and macrostructure changes over three years post-stroke.
- To investigate associations between white matter metrics and cognitive function.
- To compare white matter degeneration in stroke survivors versus controls over time.
Main Methods:
- Longitudinal fixel-based analysis of diffusion-weighted MRI data at 3, 12, and 36 months.
- Inclusion of ischemic stroke patients and age/sex-matched controls.
- Assessment of fiber density (microstructure) and cross-section (macrostructure) in relation to cognitive performance.
Main Results:
- Stroke survivors showed extensive whole-brain white matter degeneration compared to controls.
- Degeneration was prominent in thalamic, cerebellar, striatal tracts, and corpus callosum.
- Declines in fiber density and cross-section correlated with worse cognitive performance at 3 years, particularly in visuospatial processing, processing speed, language, and memory.
Conclusions:
- White matter neurodegeneration persists and is greater in stroke survivors years after the event.
- Ongoing white matter degeneration is linked to post-stroke cognitive impairment.
- Findings highlight the long-term impact of stroke on brain structure and function.
