Magnetic Resonance Imaging-Defined Cerebral Small Vessel Disease Burden and Longitudinal Neuropsychiatric and Functional Recovery After Stroke: A Prospective Cohort Study

Background/Objectives: Cerebral small vessel disease (CSVD) is an established determinant of functional outcome after stroke; however, its influence on the longitudinal course of neuropsychiatric recovery remains incompletely understood. We aimed to investigate the association between MRI-defined CSVD burden and longitudinal depressive symptom trajectories, as well as cognitive, anxiety, and functional outcomes after stroke. Methods: This prospective longitudinal cohort study included consecutive patients with acute ischemic stroke or intracerebral hemorrhage treated at a tertiary comprehensive stroke center between January 2022 and November 2025. CSVD burden was quantified using a validated MRI-based Global CSVD Score and categorized as none-to-mild (0–1) or moderate-to-severe (2–4). Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), anxiety using the Generalized Anxiety Disorder-7 (GAD-7), cognitive function using the Montreal Cognitive Assessment (MoCA), and functional outcome using the modified Rankin Scale (mRS) at baseline and 3, 6, and 9–12 months after stroke. Longitudinal depressive symptom trajectories were evaluated using linear mixed-effects models, and multivariable logistic regression was used to assess associations with incident and persistent post-stroke depression, cognitive impairment, and functional outcome. Results: Of 550 participants enrolled, 480 (87.3%) underwent brain MRI and were included in the MRI-defined CSVD analyses. Moderate-to-severe CSVD burden was associated with a less favorable longitudinal depressive symptom trajectory, reflected by a significant CSVD burden × time interaction (β = 0.68, 95% CI 0.25–1.11; p = 0.002). Moderate-to-severe CSVD burden was also independently associated with poor functional outcome (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.04–2.32; p = 0.030). In contrast, baseline CSVD burden was not independently associated with incident post-stroke depression, persistent post-stroke depression, or global cognitive impairment after multivariable adjustment. Conclusions: Greater MRI-defined CSVD burden was associated with a less favorable longitudinal depressive symptom trajectory and poorer functional recovery after stroke, whereas it was not independently associated with incident or persistent post-stroke depression or global cognitive impairment. These findings suggest that cumulative MRI-defined CSVD burden may provide complementary information regarding longitudinal emotional and functional recovery, although its incremental prognostic value and clinical utility require further validation. Multicenter studies with longer follow-up and quantitative neuroimaging are needed to confirm these associations and determine whether CSVD assessment improves risk stratification and individualized post-stroke monitoring and rehabilitation.