Magnetic Resonance Imaging-Defined Cerebral Small Vessel Disease Burden and Longitudinal Neuropsychiatric and...

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.