Objective: We attempted to better characterize pre-frailty using serum metabolomics in a large cohort of elderly subjects without neurodegenerative diseases. Next, we sought to investigate the impact of concurrent pre-frailty on elderly subjects with Parkinson’s disease (PD).
Background: Pre-frailty is a potentially reversible condition increasingly common with aging. However, whether it represents a continuum between healthy and frail status or a well-defined clinical entity is still unclear.
Method: We recruited 96 elderly non-PD subjects and classified them as non-frail, pre-frail, and frail based on Fried criteria. Untargeted metabolomics was carried out using Nuclear Magnetic Resonance (1H-NMR) on serum samples. Partial least-squares discriminant analysis and Pathway enrichment analysis were used to identify metabolites and biochemical pathways discriminating the three groups. Next, 83 mild-stage PD patients underwent Fried classification and assessment of motor and non-motor domains, ADL and QoL.
Results: Serum metabolomics identified three distinct clusters for non-frail (n=39), pre-frail (n=20), and frail (n=37) non-PD, with pre-frails showing the most evident separation from other groups [Figure 1]. Multivariate analyses revealed L-Serine, Betaine, and Histidine as the most discriminating molecules [Figure 2]. Pathway analysis pointed to dysregulation of amino acid metabolism, first of all, Serine-Glycine (p<0.001) [Figure 3]. In PD, pre-frail (n=25) patients showed intermediate levels of motor, ADL, QoL, and psychiatric impairment compared to both non-frail (n=45) and frail (n=13) subgroups (all FWER-adjusted p<0.05).
Conclusion: We identify L-Serine pathway dysregulation as a distinctive signature of pre-frailty in the elderly. In PD, pre-frailty status significantly affects both clinical phenotype and QoL, representing a potentially modifiable factor to be targeted with specific interventions.
To cite this abstract in AMA style:
A. Imarisio, M. Avenali, G. Buongarzone, M. Picascia, T. Nuzzo, C. Gasparri, F. Errico, C. Marino, M. Grimaldi, MC. Monti, A. Filosa, M. Rondanelli, C. Pacchetti, AM. D'Ursi, A. Usiello, EM. Valente. Identification of pre-frailty in the elderly through serum metabolomics and its impact on Parkinson’s disease phenotype [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/identification-of-pre-frailty-in-the-elderly-through-serum-metabolomics-and-its-impact-on-parkinsons-disease-phenotype/. Accessed May 19, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-pre-frailty-in-the-elderly-through-serum-metabolomics-and-its-impact-on-parkinsons-disease-phenotype/