Prospective Associations of Plasma Growth Differentiation Factor 15 With Physical Performance and Cognitive Functions in Older Adults

Abstract

Background: Growth differentiation factor 15 (GDF15) has been associated with several age-related disorders, but its associations with functional abilities in community-dwelling older adults are not well studied. Methods: The study was a secondary analysis of 1 096 community-dwelling older adults (aged 69-94 years) recruited from the Multidomain Alzheimer's Preventive Trial. Plasma GDF15 was measured 1 year after participants' enrollment. Annual data of physical performance (grip strength and Short Physical Performance Battery [SPPB]) and global cognitive functions (Mini-Mental State Examination [MMSE] and a composite cognitive score) were measured for 4 years. Adjusted mixed-effects linear models were performed for cross-sectional and longitudinal association analyses. Results: A higher GDF15 was cross-sectionally associated with a weaker grip strength (β = -1.1E-03, 95% CI [-2.0E-03, -1.5E-04]), a lower SPPB score (β = -3.1E-04, 95% CI [-5.4E-04, -9.0E-05]), and worse cognitive functions (β = -2.4E-04, 95% CI [-3.3E-04, -1.6E-04] for composite cognitive score; β = -4.0E-04, 95% CI [-6.4E-04, -1.6E-04] for MMSE). Participants with higher GDF15 demonstrated greater longitudinal declines in SPPB (β = -1.0E-04, 95% CI [-1.7E-04, -2.0E-05]) and composite cognitive score (β = -2.0E-05, 95% CI [-4.0E-05, -3.6E-06]). The optimal initial GDF15 cutoff values for identifying participants with minimal clinically significant decline after 1 year were 2 189 pg/mL for SPPB (AUC: 0.580) and 2 330 pg/mL for composite cognitive score (AUC: 0.587). Conclusions: Plasma GDF15 is cross-sectionally and longitudinally associated with lower-limb physical performance and global cognitive function in older adults. Circulating GDF15 alone has a limited capacity of discriminating older adults who will develop clinically significant functional declines. Clinical Trial Registration: NCT00672685