An Exploratory Study of Pathways from White Matter Hyperintensities to Cognitive Impairment through Depressive Symptoms Using Structural Equation Modeling: A Cross Sectional Study in Patients with Dementia

Abstract Objective: The aim of this study was to model the relationships among white matter hyperintensities (WMHs), depressive symptoms, and cognitive function and to examine the mediating effect of depressive symptoms on the relationship between WMHs and cognitive impairment. Methods: We performed structural equation modeling using cross-sectional data from 1158 patients from the Clinical Research for Dementia of South Korea (CREDOS) registry who were diagnosed with mild-to-moderate dementia. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were obtained separately on the protocol of magnetic resonance imaging (MRI). Depression and cognitive function were assessed using the Korean Form of the Geriatric Depression Scale (KGDS) and the Seoul Neuropsychological Screening Battery (SNSB), respectively. Results: The model that best reflected the relationships among the variables was the model in which DWMHs affected cognitive function directly and indirectly through the depressive symptoms; on the other hand, PWMHs only directly affected cognitive function. Conclusions: This study presents the mediation model including the developmental pathway from DWMHs to cognitive impairment through depressive symptoms and suggests that the two types of WMHs may affect cognitive impairment through different pathways.