Abstract
BACKGROUND: Mounting evidence support that the choroid plexus (CP) plays an important role in aging, cognition and pathogenesis of bipolar disorder (BD). However, the relationship between CP and cognitive dysfunction in older-age bipolar disorder (OABD) has not been investigated. METHODS: A total of 132 OABD patients and 130 healthy controls (HCs) from the UK Biobank were included in our analysis. Between-group differences in CP volume (CPV), gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid volume (CSV) and total brain volume (TBV) were examined. Correlation analysis was performed to explore the relationship between all volumetric measures and composite cognitive function score. By using k-means clustering algorithm, we further identified different cognitive phenotypes and investigated associated volumetric alterations. RESULTS: Compared to HCs, OABD patients showed significantly larger bilateral CPV and CSV, along with reduced GMV and TBV. For OABD patients, composite cognitive function score was negatively correlated with right CPV and CSV and positively associated with GMV and TBV. Notably, bilateral CPV enlargement was specifically associated with impaired reasoning performance. Although the linear associations between cognitive function and CPV were not corrected for false discovery rate, subgroup analyses further identified that OABD patients with poorer cognitive performance displayed greater bilateral CPV enlargement compared to those with relatively preserved cognitive function. CONCLUSION: CP abnormalities are prominent in OABD, with larger CPV linked to greater cognitive impairment, suggesting that CP may serve as a potential therapeutic target for mitigating cognitive impairment and slowing disease progression in BD. Additionally, the cognitive performance in OABD was associated with GMV, CSV and TBV, further underscoring the role of structural brain abnormalities in cognitive impairment.