Neuropsychological and behavioral correlates of cognitive function in patients with cerebral small vessel disease

Abstract Cerebral small vessel disease (CSVD) is a common cerebrovascular disorder associated with cognitive impairment and neuropsychiatric symptoms in older adults. However, the relative associations of multiple neuropsychiatric symptom domains with global cognitive function in patients with MRI-confirmed CSVD remain insufficiently characterized. This study examined the independent associations between multiple neuropsychiatric symptoms and global cognitive function in patients with MRI-confirmed CSVD. In this cross-sectional observational study, 96 individuals with MRI-confirmed CSVD were enrolled. Global cognitive function was assessed using the Persian version of the Addenbrooke’s Cognitive Examination–III (ACE-III), and neuropsychiatric symptoms were evaluated using validated Persian versions of the Depression, Anxiety and Stress Scale (DASS-21), the Buss–Perry Aggression Questionnaire (BPAQ), and the Pittsburgh Sleep Quality Index (PSQI). Pearson correlation analyses with false discovery rate correction and multiple linear regression analyses were performed. Pearson correlation analyses demonstrated negative associations between global cognitive function and several neuropsychiatric symptoms. After false discovery rate correction using the Benjamini–Hochberg procedure, significant associations remained for depressive and anxiety symptoms, whereas associations involving perceived stress and aggression no longer met the corrected significance threshold. Sleep disturbance was not significantly associated with global cognitive function in the correlation analyses. In the multivariable regression model, which explained 57.4% of the variance in global cognitive function (R² = 0.574), sleep disturbance (β = −0.267, p = 0.002), depressive symptoms (β = −0.265, p = 0.009), anxiety symptoms (β = −0.224, p = 0.033), and perceived stress (β = −0.192, p = 0.039) were independently associated with poorer global cognitive function, whereas aggression was not independently associated. Sleep disturbance, depressive symptoms, anxiety symptoms, and perceived stress were independently associated with poorer global cognitive function in patients with MRI-confirmed CSVD. These findings suggest that assessment of neuropsychiatric symptoms may provide clinically relevant information when evaluating cognitive function in patients with CSVD and support the potential value of comprehensive neuropsychiatric assessment as part of routine clinical evaluation. However, because of the cross-sectional design, these findings do not establish causal relationships. Longitudinal studies are needed to clarify the temporal relationships between neuropsychiatric symptoms and cognitive changes.