Role of glymphatic system function in cognitive dysfunction among patients with bipolar disorder

Abstract Objective Increasing evidence has suggested a potential role of glymphatic system function in the pathomechanisms underlying mood disorders and related cognitive impairment. However, this association in bipolar disorder remained unclear. Design, Participants, and Measures In all, 185 patients (mean age ~ 30 years) with bipolar disorder and 95 healthy individuals were enrolled for the assessment of the go/no-go task and the digit symbol substitution test (DSST). The Analysis Along the Perivascular Space (ALPS) index, an indicator of glymphatic system activity, was measured using diffusion tensor imaging within diffusion magnetic resonance imaging. All participants were divided into two subgroups (< vs. ≥ mean level) based on the mean ALPS index level. Additionally, participants were further categorized into quartiles based on ALPS index levels, ranging from Q1 (highest) to Q4 (lowest). Results Generalized linear model, after adjusting for age, sex, education years, and clinical symptoms, found no difference in the ALPS index levels between patients and controls. Patients with lower ALPS index levels—that is, those with values below the mean or in the lowest quartile (Q4)—performed the worst on the DSST and the go/no-go task. Conclusions and Relevance Glymphatic system dysfunction appeared to play a critical role in cognitive impairment among patients with bipolar disorder, but not in healthy individuals. Further research is warranted to clarify the specific pathomechanisms underlying this bipolar disorder–specific association between glymphatic system dysfunction and cognitive deficits.