The Effect of Neuroepo on Cognition in Parkinson’s Disease Patients Is Mediated by Electroencephalogram Source Activity

• DOI: 10.3389/fnins.2022.841428
• Publication Date: 2022-06-30T09:15:55Z
• Authors: Maria L. Bringas ...; Ivonne Pedroso Ib...; 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
• Keywords: Developmental psychology; FOS: Political science; source analysis; Neurosciences. Biological psychiatry. Neuropsychiatry; FOS: Law; Role of Erythropoietin in Disease Treatment and Management; Structural equation modeling; Neuroepo; Cellular and Molecular Neuroscience; 03 medical and health sciences; Cognition; 0302 clinical medicine; whitening; Neuropsychology; Health Sciences; FOS: Mathematics; Psychology; EEG; Cognitive test; Internal medicine; Political science; Statistics; Mediation; Life Sciences; Neural Interface Technology; Hematology; Audiology; Neuroprotection; 3. Good health; Canonical Correlation Analysis (CCA); FOS: Psychology; Neurology; Parkinson’s disease; Medicine; Law; Pathophysiology of Parkinson's Disease; Mathematics; RC321-571; Neuroscience

We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson’s disease (PD) from a double-blind safety trial (https://clinicaltrials.gov/, number 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.