The Effect of Neuroepo on Cognition in Parkinson's Disease Patients Is Mediated by Electroencephalogram Source Activity
Maria L Bringas Vega, Ivonne Pedroso Ibáñez, Fuleah A Razzaq, Min Zhang, Lilia Morales Chacón, Peng Ren, Lidice Galan Garcia, Peng Gan, Trinidad Virues Alba, Carlos Lopez Naranjo, Marjan Jahanshahi, Jorge Bosch-Bayard, Pedro A Valdes-Sosa, Maria L Bringas Vega, Ivonne Pedroso Ibáñez, Fuleah A Razzaq, Min Zhang, Lilia Morales Chacón, Peng Ren, Lidice Galan Garcia, Peng Gan, Trinidad Virues Alba, Carlos Lopez Naranjo, Marjan Jahanshahi, Jorge Bosch-Bayard, Pedro A Valdes-Sosa
Abstract
We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson's disease (PD) from a double-blind safety trial (https://ichgcp.net/clinical-trials-registry/NCT04110678" title="See in ClinicalTrials.gov">NCT04110678). Neuroepo is a new erythropoietin (EPO) formulation with a low sialic acid content with satisfactory results in animal models and tolerance in healthy participants and PD patients. In this study, 26 PD patients were assigned randomly to Neuroepo (n = 15) or placebo (n = 11) groups to test the tolerance of the drug. Outcome variables were neuropsychological tests and resting-state source qEEG at baseline and 6 months after administering the drug. Probabilistic Canonical Correlation Analysis was used to extract latent variables for the cognitive and for qEEG variables that shared a common source of variance. We obtained canonical variates for Cognition and qEEG with a correlation of 0.97. Linear Mixed Model analysis showed significant positive dependence of the canonical variate cognition on the dose and the confounder educational level (p = 0.003 and p = 0.02, respectively). Additionally, in the mediation equation, we found a positive dependence of Cognition with qEEG for (p = < 0.0001) and with dose (p = 0.006). Despite the small sample, both tests were powered over 89%. A combined mediation model showed that 66% of the total effect of the cognitive improvement was mediated by qEEG (p = 0.0001), with the remaining direct effect between dose and Cognition (p = 0.002), due to other causes. These results suggest that Neuroepo has a positive influence on Cognition in PD patients and that a large portion of this effect is mediated by brain mechanisms reflected in qEEG.
Keywords: Canonical Correlation Analysis (CCA); EEG; Neuroepo; Parkinson’s disease; source analysis; whitening.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Copyright © 2022 Bringas Vega, Pedroso Ibáñez, Razzaq, Zhang, Morales Chacón, Ren, Galan Garcia, Gan, Virues Alba, Lopez Naranjo, Jahanshahi, Bosch-Bayard and Valdes-Sosa.
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References
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