White matter integrity and cognitive performance in the subacute phase after ischemic stroke in young adults

Reduced white matter integrity outside the stroke lesion may be a potential contributor of post-stroke cognitive impairment. We aimed to investigate how a stroke lesion affects the integrity of surrounding white matter, and whether the integrity of the non-lesioned part of white matter tracts is associated with cognitive performance after ischemic stroke in young adults.

Patients from the ODYSSEY study, aged 18-49 years, with a first-ever ischemic stroke, underwent 3T MRI and cognitive assessment within six months after the index event. Using TractSeg and free water imaging, we analyzed free water corrected fractional anisotropy (FA_T), free water corrected mean diffusivity (MD_T), and free water (FW) of all white matter tracts outside the stroke lesion. We calculated FA_T and FW in the lesioned white matter tracts at 2 mm incremental distances from the lesion, extending up to 10 mm, represented as Z-scores using the diffusion measures of controls. We categorized patients as no/mild or major vascular cognitive disorder (VCD) and compared with a stroke-free control group (n = 23). Group differences in diffusion measures were examined. We investigated associations between FA_T, FW and cognitive performance across seven domains.

Among 66 patients (median age 40.3 years (IQR 31.3-46.2); 54.5 % women), 22 had major VCD. In the different lesion expansions, we found differences in FA_T (p = 0.009) and FW (p = 0.049). Patients with major VCD had lower FA_T [range of Cohen's d (0.65; 1.65)] and higher FW [Cohen's d (-1.40; -0.64)] values compared to controls, both in the hemisphere affected by the lesion and the unaffected hemisphere. Performance in processing speed correlated with FA_T across eight tracts in the affected hemisphere [range of R²_adj (0.30; 0.37)], and with FW in four tracts in the affected and three in the unaffected hemisphere [R²_adj (0.28; 0.38)].

In the first months after a stroke, we observed a trend of microstructural changes remote from the lesion that diminish as the distance from the lesion increases. Tissue changes in the white matter outside the lesion are present in both hemispheres, but are more pronounced in the hemisphere affected by the stroke, and may contribute to worse cognitive performance.