THE ASSOCIATION OF KLOTHO/FIBROBLAST GROWTH FACTOR 23 WITH COGNITIVE FEATURES IN ELDERLY PATIENTS WITH BIPOLAR DISORDER

Abstract Background Cognitive aging is a known phenomenon in individuals with bipolar disorder (BD), but the underlying biological mechanisms responsible for this cognitive decline remain poorly understood. One potential avenue of investigation is the dysfunction of the Klotho/Fibroblast Growth Factor 23 (FGF23) system, which has been linked to reduced lifespan and age-related diseases, including dementia. However, there is limited research on the relationship between Klotho/FGF23 levels and aging in BD patients, as well as their association with cognitive decline in elderly individuals with BD. Aims The aim of this study was to explore the levels of Klotho and FGF23 in elderly BD patients and their relationship with the aging profile and cognitive domains. Methods The study included 85 euthymic, elderly participants aged 50 or older, who also had adequate kidney function and were diagnosed with BD-I. Cognitive function was assessed using the Brief Assessment of Cognition in Affective Disorders. The study examined the correlations between Klotho and FGF23 levels and other aging-related assessments. General linear models were then used to identify associations between Klotho and FGF23 levels and various cognitive domains. Results The average age of the participants was 59.64 years. The mean Klotho and FGF23 levels were 0.71 ng/ml and 15.02 ng/ml, respectively. Positive correlations were found between Klotho and FGF23 (r= 0.352, p = 0.002) and between creatine levels and Klotho/FGF23 (r = 0.328, p = 0.016 for Klotho and r= 0.302, p = 0.028 for FGF23). Higher levels of FGF23 were significantly associated with lower composite cognitive scores (β= -0.003, p = 0.005), particularly in verbal memory (β= -0.002, p = 0.013), motor speed (β= -0.002, p = 0.027), and processing speed (β= -0.002, p = 0.029). No significant association was observed between Klotho levels and cognitive domains. Conclusion In elderly individuals with BD, this study found that higher FGF23 levels were associated with negative effects on cognitive domains, particularly in verbal memory, motor speed, and processing speed. However, no significant association was found between Klotho levels and cognitive performance. Future research is needed to further define the dysfunction of the Klotho/FGF23 axis and conduct longitudinal studies that incorporate validated aging clinical markers to better understand the underlying mechanisms of cognitive aging in BD.