Objective: To investigate possible associations between serum metabolomic profiles and non-motor symptoms (NMS) frequency and intensity in PD patients

Background: Metabolomic studies are providing growing evidence on how metabolism in PD may be impaired. Their relationship with the occurrence of non-motor symptoms is not yet well established.

Method: This is an observational, cross-sectional, exploratory study conducted with 54 patients in stages 1 to 3 of the Hoehn & Yahr Scale. NMS were assessed using the MDS Non-Motor Rating Scale, and clinical profiles were identified by cluster analysis (K-means). Serum samples were analyzed by 1H Magnetic resonance spectroscopy, and multivariate modeling (O-PLS-DA) was used to discriminate metabolites associated with the different clinical profiles.

Results: Cluster analysis revealed three distinct patient groups—mild, intermediate, and severe. Groups were compared regarding age, sex, disease duration, LEED, and Schwab & England scores, with no differences detected between groups. Regarding non-motor symptoms, significant differences (p<0.001) were found mainly in depression, anxiety, apathy, gastrointestinal symptoms, sleep, and pain. Metabolomic modeling distinguished two clinical profiles, showing higher serum levels of tyrosine and formate in patients with a more severe profile, while those with fewer symptoms presented higher concentrations of fatty acids, glycerol, citrate, and sugars. The model showed excellent statistical performance, with a total explained variation of 88.3%. Higher formate levels may indicate more significant abnormalities in mitochondrial metabolism in this group with more pronounced non-motor symptoms. Tyrosine may be elevated due to reduced central utilization, indicating lower central availability of levodopa. Patients with milder non-motor symptoms presented higher levels of fatty acids and glycerol compared to the other cluster, possibly reflecting a more preserved metabolic and structural profile, with partial maintenance of lipid oxidation and mitochondrial function.

Conclusion: The results indicate that the serum metabolomic profile is associated with the severity of non-motor symptoms in PD, and that metabolites such as tyrosine and formate may represent potential biomarkers of higher non-motor burden, especially for emotional, cognitive, and gastrointestinal symptoms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/metabolomic-profile-as-a-biomarker-of-non-motor-symptoms-severity-in-patients-with-parkinsons-disease/