Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: A multicenter study in 1568 stroke patients

Abstract

Background: Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear.

Aims: We determined if WMH in strategic white matter tracts explain cognitive performance after stroke.

Methods: Individual patient data from nine ischemic stroke cohorts with magnetic resonance imaging (MRI) were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus.

Results: The total study sample consisted of 1568 patients (39.9% female, mean age = 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume.

Conclusion: These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH.

Data access statement: The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

Keywords: White matter hyperintensities; post-stroke cognition; strategic lesion location.

Figure 1.

Flowchart of patient selection. This figure shows the flowchart of patient selection for the nine participating cohorts. This figure was previously published in Stroke.

Figure 2.

Infarct and WMH prevalence maps shown per infarct subtype. This figure shows how often each location in the brain was affected by an acute infarct or WMH. Blue voxels are damaged in one patient and red voxels in >40 patients. Results are presented per infarct subtype (i.e. small subcortical infarcts, large subcortical and cortical infarcts, and infratentorial infarcts). For each infarct subtype, the first row represents the infarct prevalence map and the second row represents the WMH prevalence map. Patients with multiple infarcts can be represented in more than one stroke category.