ABSTRACT Aim Growth differentiation factor‐15 (GDF‐15) is a biomarker reflecting aging and cellular stress, associated with physical frailty and cognitive decline. We cross‐sectionally examined whether physical frailty is involved in the association between GDF‐15 and cognitive decline. Understanding this association may help to consider frailty‐related cognitive decline and potential preventive approaches. Methods This cross‐sectional study included 134 participants aged 65 years or older, excluding those with severe renal dysfunction, immune‐related diseases, and those with dementia or suspected dementia (Mini‐Mental State Examination MMSE score ≤ 23). Serum GDF‐15 levels were measured, and cognitive decline was assessed using the MMSE with a cutoff score of 27 or lower. Physical frailty was evaluated using the revised Japanese Cardiovascular Health Study criteria comprising five components: shrinking, exhaustion, weakness, slowness, and low activity. Results A mediation analysis adjusted for age, sex, and education showed a significant indirect effect of GDF‐15 on cognitive decline through physical frailty (β = 0.921, 95% confidence interval CI: 0.279–1.560). The total effect was also significant (β = 1.020, 95% CI: 0.030–2.010), whereas the direct effect was not significant (β = 0.100, 95% CI: −0.991 to 1.190). Conclusions This study suggests a potential involvement of physical frailty in the relationship between serum GDF‐15 levels and cognitive decline. Serum GDF‐15 levels may have potential as a clinical indicator for frailty‐related cognitive decline in the future. Further longitudinal studies are needed to explore this relationship and clarify the role of GDF‐15.
Yoshiura et al. (Sun,) studied this question.