Association of Physical Frailty With Serum Growth Differentiation Factor‐15 and Cognitive Decline: A Cross‐Sectional Study

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.