Objective: The purpose of this study was to determine potential biofluid biomarkers for cognitive impairment in a cohort of Parkinson’s disease (PD) patients. Here we utilized lipidomic assessment in participant biofluids to assess correlation with cognitive profiles.

Background: Cognitive impairment in PD is a devastating but all too common development, affecting 50-80% of PD patients, with a concurrent increase in morbidity and mortality, and significant impact on caregiver burden. The ability to prognosticate cognitive trajectory in PD would shape treatment and stratify candidacy for emerging disease-modifying therapeutics. Lipidomics is a powerful platform for analyzing underlying changes in metabolic pathways with the potential for expanding opportunities for biomarker identification. Alterations in sphingolipids and ceramides affect mitochondrial function, autophagy and endosomal trafficking, all functions that show dysregulation in PD.

Method: Patients seen in Kentucky Neuroscience Institute Movement Disorder Clinic with a diagnosis of idiopathic PD were consented under an IRB-approved protocol and enrolled. PD patients (n=28) with normal cognition or mild cognitive impairment underwent serial sample collection, cognitive, and motor testing. EDTA blood samples were drawn and processed immediately after collection. Plasma was aliquoted and stored at -80,  Lipidomics analysis was conducted in a single batched analysis on biofluid samples by our CNS-Met Metabolomics Core at University of Kentucky.

Results: A cognitive z-score variable was developed to reflect contributions from six different cognitive domains tested and to create a continuous variable for cognition. Targeted lipidomic analyses identified 2 phosphatidylethanomine species that decreased in abundance in individuals with higher cognitive scores. C16 Ceramide-1-phosphate and Sphingosine-1-phosphate were positively correlated with cognitive z-scores. Cer 17:1/20:0 was negatively correlated with the cognitive z-score in PD individuals.

Conclusion: This study suggests that biofluid lipidomic analysis is useful for the identification of lipids, including specific ceramides and sphingolipids which may reflect cognitive function in Parkinson’s disease. Limitations of this study include a small initial “n” for assessment and longitudinal results (which are in progress). Future studies include the need for validation in larger cohorts.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/biofluid-markers-in-parkinsons-patients-and-correlation-with-cognitive-profile/