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

• Wen-Yin Chen ^[2] ; Chih Chiang Chiu ^[3] ; Po-Hsiu Kuo ^[4] ; Cho-Yin Huang ^[5] ; Shang-Ying Tsia ^[6] ; Chian-Jue Kuo ^[7] ; Ying-Chih Cheng ^[1] ; Po-Yu Chen ^[3] ; Ming-Chyi Huang ^[3]
  1. [1] China Medical University

     China Medical University

     Taiwán

     
  2. [2] Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan
  3. [3] Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan. Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  4. [4] Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan
  5. [5] Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan. Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei, Taiwan
  6. [6] Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan
  7. [7] Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan. Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan

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• Localización: European journal of psychiatry, ISSN 0213-6163, Vol. 39, Nº 4, 2025
• Idioma: inglés
• DOI: 10.1016/j.ejpsy.2025.100320
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  • 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.