Association between frontal pole atrophy and glymphatic dysfunction in patients with bipolar disorder

Patients with bipolar disorder (BD) are highly at risk for dementia and may develop brain atrophy, which is linked to cognitive decline. One possible reason for brain atrophy is cellular damage resulting from waste product accumulation caused by glymphatic dysfunction. This study evaluated the glymphatic system in patients with BD, using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and choroid plexus volume (CPV) in two separate BD cohorts. The insight into whether these clearance indices were associated with brain atrophy was also investigated.

The discovery cohort consisted of 28 patients with BD and 28 healthy controls (HCs). The validation cohort included 42 patients with BD and 42 HCs. BD group and HCs in both cohorts underwent group comparisons of the ALPS index, CPV relative to the total intracranial volume (CPV/TIV), and brain gray matter volume. The relationships between the ALPS index and frontal pole volume were determined.

The ALPS index decreased in BD group compared with that in HCs in both cohorts (p < 0.05). While BD group showed increased CPV/TIV and frontal pole atrophy in the discovery cohort, such increase was insignificant in the validation cohort. In the discovery cohort, frontal pole atrophy was related to the ALPS index decrement (r = 0.34, p = 0.02), and the ALPS index-mediated frontal pole atrophy was associated with BD.

Middle-aged patients with BD may experience dysfunction in the excretory pathway of the perivascular space around the medullary veins, likely contributing to frontal pole atrophy.