Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke

Abstract

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 to stroke-free participants, but longitudinal changes in the structure of white matter after stroke remain largely unexplored. We aimed to characterise 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, transient ischemic attack, 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 analysed 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 to 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 (FWE-corrected p<0.05, non-parametric testing over 5000 permutations).Results:We included 71 stroke (age 66±12, 22 women) and 36 control participants (age 69±5, 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 pre-defined 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 contra-lesional- thalamic, striatal and cerebellar tracts continues to be greater in stroke survivors compared to stroke-free controls. White matter degeneration persists even years after stroke and is associated with post-stroke cognitive impairment.

Structural Neuroplasticity Effects of Singing in Chronic Aphasia

“…In comparison, the mean left BA44 GM volume decrease in the control group in the present study was 140 mm 3 in 5 months. Similarly, WM neurodegeneration in ipsi- and contralesional tracts continues to be greater in stroke survivors compared with the healthy population ( Egorova-Brumley et al, 2023 ). In a recent study on patients with PSA, most patients showed evidence of lesion expansion and that it was associated with further declining language performance ( Johnson et al, 2023 ).…”

Mechanisms of glutamate metabolic function and dysfunction in vascular dementia

“…Immediate or delayed VCI or VaD affects 25–30% of ischemic stroke survivors, and pathologic and imaging studies indicate that VaD accounts for 70% of poststroke dementia 25 . A study comparing 71 patients with stroke with 36 healthy individuals of the same age revealed that patients with stroke experienced extensive structural degeneration of the white matter of the entire brain and gradually developed cognitive problems 3 months after the stroke 26 . Cerebral amyloid angiopathy, a common small vessel disease, can cause VaD by activating vascular damage or inflammatory pathways that impair vascular physiology or increase the risk of stroke 27,28 .…”

“…25 A study comparing 71 patients with stroke with 36 healthy individuals of the same age revealed that patients with stroke experienced extensive structural degeneration of the white matter of the entire brain and gradually developed cognitive problems 3 months after the stroke. 26 Cerebral amyloid angiopathy, a common small vessel disease, can cause VaD by activating vascular damage or inflammatory pathways that impair vascular physiology or increase the risk of stroke. 27,28 Acupuncture can help reduce VCI by inhibiting the mir-93-mediated toll-like receptors 4/myeloid differentiation factor 88/nuclear factor kappa-B inflammatory signaling pathway.…”

Probing Evidence of Cerebral White Matter Microstructural Disruptions in Ischemic Heart Disease Before and Following Cardiac Rehabilitation: A Diffusion Tensor MR Imaging Study

“…Although TractSeg allows along-tract quantification of 50 WM bundles, the tractometry analysis was primarily focused on 8 WM bundles linked to impairment in higher-order cognitive functions (executive function, information processing speed, verbal memory) in IHD post-MI [1][2][3] : left/right cingulum (CG), left/right inferior fronto-occipital fasciculus (IFOF), left/right inferior longitudinal fasciculus (ILF), and left/right uncinate fasciculus (UF). In addition, tractometry was performed on 10 other WM bundles generally implicated in post-ischemic cerebrovascular injury and cognitive decline 24 : left/right arcuate fasciculus (AF), rostrum and splenium of the corpus callosum (CC), left/right superior longitudinal fasciculus (SLF) I, left/right SLF II, and left/ right SLF III. Thus, a total of 18 WM bundles related to vascular cognitive impairment were analyzed by tractometry in this study.…”