Long-Term Post-Stroke Cognition in Patients With Minor Ischemic Stroke is Related to Tract-Based Disconnection Induced by White Matter Hyperintensities

Abstract

Over a third of minor stroke patients experience post-stroke cognitive impairment (PSCI), but no validated tools exist to identify at-risk patients early. This study investigated whether disconnection features derived from infarcts and white matter hyperintensities (WMH) could serve as markers for short- and long-term cognitive decline in first-ever minor ischemic stroke patients. First-ever minor ischemic stroke patients (NIHSS ≤ 7) were prospectively followed at 72-h, 6 months, and 36 months post-stroke with cognitive tests and brain MRI. Infarct and WMH volumes were semi-automatically assessed on DWI and FLAIR sequences. Bayesian tract-based disconnection models estimated remote pathological effects of infarcts and WMH. Associations between disconnection features and cognitive outcomes were analyzed using canonical correlation analyses, adjusted for age, education, and multiple comparisons. Among 105 patients (31% female, mean age 63 ± 12 years), infarct volume averaged 10.28 ± 17.10 cm³ and predominantly involved the middle cerebral artery territory (83%). WMH burden was higher in frontal periventricular white matter. Infarct-based features did not significantly relate to PCSI. However, a WMH-derived disconnection factor, involving commissural and frontal tracts, and the right superior longitudinal fasciculus, was significantly associated with PSCI at 6 months (OR = 9.96, p value = 0.02) and 36 months (OR = 12.27, p value = 0.006), particularly in executive/attention, language, and visuospatial domains. This factor, unrelated to WMH volume, outperformed demographic and clinical predictors of PSCI. WMH-induced disconnection may be associated with short- and long-term PSCI in minor stroke. Routine MR-derived features could identify at-risk patients for rehabilitation trials.