Cortical thinning 3 years after ischaemic stroke is associated with cognitive impairment and APOE ε4

Cortical thinning has been described in many neurodegenerative diseases and used for both diagnosis and disease monitoring. The imaging signatures of post-stroke vascular cognitive impairment have not been well described. We investigated the trajectory of cortical thickness over 3 years following ischaemic stroke compared to healthy stroke-free age- and sex-matched controls. We also compared cortical thickness between cognitively normal and impaired stroke survivors, and between APOE ɛ4 carriers and non-carriers. T1-weighted MRI and cognitive data for 90 stroke survivors and 36 controls from the Cognition And Neocortical Volume After Stroke (CANVAS) study were used. Cortical thickness was estimated using FreeSurfer volumetric reconstruction according to the Desikan-Killiany parcellation atlas. Segmentation inaccuracies were manually corrected and infarcted ipsilesional vertices in cortical thickness maps were identified and excluded using stroke lesion masks traced a-priori. Mixed-effects regression was used to compare cortical thickness cross-sectionally between groups and longitudinally between timepoints. Healthy control and stroke groups did not differ on demographics and most clinical characteristics, though controls were less likely to have atrial fibrillation. Age was negatively associated with global mean cortical thickness independent of sex or group, with women in both groups having significantly thicker cortex. Three months post-stroke, cortical thinning was limited and focal. From 3 months to 3 years, the rate of cortical thinning in stroke was faster compared to that in healthy controls. However, this difference in cortical thinning rate could not survive family-wise correction for multiple comparisons. Yet, cortical thinning at 3 years was found more spread especially in ipsilesional hemispheres in regions implicated in motor, sensory, and memory processing and recovery. The cognitively impaired stroke survivors showed greater cortical thinning, compared to controls, than those who were cognitively normal at 3 years. Also, carriers of the APOE ɛ4 allele in stroke exhibited greater cortical thinning independent of cognitive status. The temporal changes of cortical thickness in both healthy and stroke cohorts followed previously reported patterns of cortical thickness asymmetry loss across the human adult life. However, this loss of thickness asymmetry was amplified in stroke. The post-stroke trajectories of cortical thickness reported in this study may contribute to our understanding of imaging signatures of vascular cognitive impairment.