# Associations Between Growth Differentiating Factor‐15 and Frailty in Older Adults From the MAPT Study

## TL;DR

Higher levels of GDF-15 in older adults are linked to frailty, suggesting it could be a useful biomarker for identifying those at risk.

## Contribution

This study provides new evidence on the association between GDF-15 and frailty in older adults.

## Key findings

- Higher GDF-15 levels were cross-sectionally associated with frailty (OR = 3.56).
- Very high GDF-15 levels predicted an increased risk of incident frailty (HR = 1.69).
- Low physiological levels of GDF-15 do not contribute to frailty development.

## Abstract

Frailty is a prevalent syndrome in older adults and is associated with increased vulnerability to adverse health outcomes. Growth differentiation factor 15 (GDF‐15), a cytokine involved in mitochondrial dysfunction and inflammation, has been proposed as a potential biomarker for age‐related conditions. Evidence on the association between GDF‐15 and frailty in older adults is limited. This study explores the relationship between plasma GDF‐15 levels and frailty onset in community‐dwelling older adults.

A secondary analysis was performed on 1096 participants (mean age = 75.2 ± 4.5 years; 64.5% women) from the Multidomain Alzheimer Prevention Trial (MAPT). Plasma GDF‐15 levels were measured at year 1. Frailty was assessed using the Fried phenotype. Logistic regression was used to examine cross‐sectional associations between GDF‐15 and frailty, while mixed effects logistic regression or Cox proportional hazards models assessed longitudinal associations over a 4‐year follow‐up.

Higher plasma GDF‐15 levels (both as continuous and categorical) were cross‐sectionally associated with frailty (high vs. low GDF‐15: OR = 3.56, 95% CI = 1.58–8.03). Longitudinally, very high GDF‐15 levels predicted an increased risk of incident frailty (HR = 1.69, 95% CI = 1.03–2.78).

Elevated plasma GDF‐15 levels were associated with frailty in older adults, suggesting its potential as a biomarker for increased vulnerability and an indicator of increased risk over time. Our results support a pleiotropic role of GDF‐15, with low physiological levels not contributing to frailty development.