The association of α-klotho/fibroblast growth factor 23 with cognitive features in euthymic older age patients with bipolar disorder

Abstract

Background and objectives

Cognitive aging is common among bipolar disorder (BD). The α-klotho/fibroblast growth factor 23 (FGF23) system has been associated with neuropsychiatric disorders and age-related diseases. This study aimed to investigate α-klotho and FGF23 levels in older-age bipolar disorder (OABD) and examine their associations with aging-related characteristics and cognitive function.

Methods

This study included 87 euthymic OABD, 83 younger-age bipolar disorder (YABD), and 20 healthy controls, to assess α-klotho and FGF23 levels. In OABD group, cognitive function was evaluated using the Brief Assessment of Cognition in Affective Disorders. Aging-related features were assessed, including daily physical activity, grip strength, and the Framingham Risk Score. We examined the correlations between α-klotho/FGF23 levels and aging-related features and explored their associations with cognitive domains in OABD.

Results

The FGF23 levels in OABD were lower compared to those in YABD. The α-klotho levels were not significantly different between three groups. A negative association was observed between FGF23 and global cognitive composite scores (B = -0.006, p = 0.005), particularly in motor speed (B = -0.006, p = 0.001), working memory (B = -0.007, p = 0.006), and verbal fluency (B = -0.002, p = 0.049). Additionally, α-klotho levels were positively associated with working memory (B = 0.735, p = 0.039).

Conclusions

FGF23 had a negative impact on cognitive domains, while α-klotho was positively associated with working memory in OABD. Future research should investigate the dysfunction of the α-klotho/FGF23 axis and incorporate additional validated aging markers in longitudinal studies to confirm the proposed biomarker relationships.