Evaluation of Parkinson’s disease early diagnosis using single-channel EEG features and auditory cognitive assessment

BackgroundParkinson’s disease (PD) often presents with subtle early signs, making diagnosis difficult. F-DOPA PET imaging provides a reliable measure of dopaminergic function and is a primary tool for early PD diagnosis. This study aims to evaluate the ability of machine-learning (ML) extracted EEG features to predict F-DOPA results and distinguish between PD and non-PD patients. These features, extracted using a single-channel EEG during an auditory cognitive assessment, include EEG feature A0 associated with cognitive load in healthy subjects, and EEG feature L1 associated with cognitive task differentiation.MethodsParticipants in this study are comprised of cognitively healthy patients who had undergone an F-DOPA PET scan as a part of their standard care (n = 32), and cognitively healthy controls (n = 20). EEG data collected using the Neurosteer system during an auditory cognitive task, was decomposed using wavelet-packet analysis and machine learning methods for feature extraction. These features were used in a connectivity analysis that was applied in a similar manner to fMRI connectivity. A preliminary model that relies on the features and their connectivity was used to predict initially unrevealed F-DOPA test results. Then, generalized linear mixed models (LMM) were used to discern between PD and non-PD subjects based on EEG variables.ResultsThe prediction model correctly classified patients with unrevealed scores as positive F-DOPA. EEG feature A0 and the Delta band revealed distinct activity patterns separating between study groups, with controls displaying higher activity than PD patients. In controls, EEG feature L1 showed variations between resting state and high-cognitive load, an effect lacking in PD patients.ConclusionOur findings exhibit the potential of single-channel EEG technology in combination with an auditory cognitive assessment to distinguish positive from negative F-DOPA PET scores. This approach shows promise for early PD diagnosis. Additional studies are needed to further verify the utility of this tool as a potential biomarker for PD

Description of the Method for Evaluating Digital Endpoints in Alzheimer Disease Study : Protocol for an Exploratory, Cross-sectional Study

©Jelena Curcic, Vanessa Vallejo, Jennifer Sorinas, Oleksandr Sverdlov, Jens Praestgaard, Mateusz Piksa, Mark Deurinck, Gul Erdemli, Maximilian Bügler, Ioannis Tarnanas, Nick Taptiklis, Francesca Cormack, Rebekka Anker, Fabien Massé, William Souillard-Mandar, Nathan Intrator, Lior Molcho, Erica Madero, Nicholas Bott, Mieko Chambers, Josef Tamory, Matias Shulz, Gerardo Fernandez, William Simpson, Jessica Robin, Jón G Snædal, Jang-Ho Cha, Kristin Hannesdottir. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 10.08.2022.BACKGROUND: More sensitive and less burdensome efficacy end points are urgently needed to improve the effectiveness of clinical drug development for Alzheimer disease (AD). Although conventional end points lack sensitivity, digital technologies hold promise for amplifying the detection of treatment signals and capturing cognitive anomalies at earlier disease stages. Using digital technologies and combining several test modalities allow for the collection of richer information about cognitive and functional status, which is not ascertainable via conventional paper-and-pencil tests. OBJECTIVE: This study aimed to assess the psychometric properties, operational feasibility, and patient acceptance of 10 promising technologies that are to be used as efficacy end points to measure cognition in future clinical drug trials. METHODS: The Method for Evaluating Digital Endpoints in Alzheimer Disease study is an exploratory, cross-sectional, noninterventional study that will evaluate 10 digital technologies' ability to accurately classify participants into 4 cohorts according to the severity of cognitive impairment and dementia. Moreover, this study will assess the psychometric properties of each of the tested digital technologies, including the acceptable range to assess ceiling and floor effects, concurrent validity to correlate digital outcome measures to traditional paper-and-pencil tests in AD, reliability to compare test and retest, and responsiveness to evaluate the sensitivity to change in a mild cognitive challenge model. This study included 50 eligible male and female participants (aged between 60 and 80 years), of whom 13 (26%) were amyloid-negative, cognitively healthy participants (controls); 12 (24%) were amyloid-positive, cognitively healthy participants (presymptomatic); 13 (26%) had mild cognitive impairment (predementia); and 12 (24%) had mild AD (mild dementia). This study involved 4 in-clinic visits. During the initial visit, all participants completed all conventional paper-and-pencil assessments. During the following 3 visits, the participants underwent a series of novel digital assessments. RESULTS: Participant recruitment and data collection began in June 2020 and continued until June 2021. Hence, the data collection occurred during the COVID-19 pandemic (SARS-CoV-2 virus pandemic). Data were successfully collected from all digital technologies to evaluate statistical and operational performance and patient acceptance. This paper reports the baseline demographics and characteristics of the population studied as well as the study's progress during the pandemic. CONCLUSIONS: This study was designed to generate feasibility insights and validation data to help advance novel digital technologies in clinical drug development. The learnings from this study will help guide future methods for assessing novel digital technologies and inform clinical drug trials in early AD, aiming to enhance clinical end point strategies with digital technologies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35442.Peer reviewe

DJ-1 based peptide, ND-13, promote functional recovery in mouse model of focal ischemic injury.

Stroke is a leading cause of death worldwide and inflicts serious long-term damage and disability. The vasoconstrictor Endothelin-1, presenting long-term neurological deficits associated with excitotoxicity and oxidative stress is being increasingly used to induce focal ischemic injury as a model of stroke. A DJ-1 based peptide named ND-13 was shown to protect against glutamate toxicity, neurotoxic insults and oxidative stress in various animal models. Here we focus on the benefits of treatment with ND-13 on the functional outcome of focal ischemic injury. Wild type C57BL/6 mice treated with ND-13, after ischemic induction in this model, showed significant improvement in motor function, including improved body balance and motor coordination, and decreased motor asymmetry. We found that DJ-1 knockout mice are more sensitive to Endothelin-1 ischemic insult than wild type mice, contributing thereby additional evidence to the widely reported relevance of DJ-1 in neuroprotection. Furthermore, treatment of DJ-1 knockout mice with ND-13, following Endothelin-1 induced ischemia, resulted in significant improvement in motor functions, suggesting that ND-13 provides compensation for DJ-1 deficits. These preliminary results demonstrate a possible basis for clinical application of the ND-13 peptide to enhance neuroprotection in stroke patients

Experimental protocol and ischemic injury location.

<p>Experimental protocol in days (A). The vasoconstrictor Endothelin-1 was injected into the striatum to induce ischemia. The ischemic area in the striatum is circled in black (B).</p

Changes in mitochondrial protein expression levels following ND-13 treatment.

<p>Ischemic wild type mice treated with ND-13 show significant change in protein expression levels compared to saline treated ischemic wild type mice. SDHAF4 protein levels increased after ND-13 treatment (A, FC = 107.4, p<0.001). Ubiquinone protein levels decreased after ND-13 treatment (B, FC = 3.5, p<0.01). Rhot2 protein levels decreased after ND-13 treatment (C, FC = 2.5, p<0.01). Usp35 protein levels decreased after ND-13 treatment (D, FC = 2.4, p<0.01). (Data is shown as mean ± SEM).</p

DJ-1 KO mice show higher sensitivity and less spontaneous recovery after ischemic injury compared to C57BL/6 mice.

<p>DJ-1 KO mice show slower spontaneous recovery compared to C57BL/6 mice and are more sensitive to ischemic insult. DJ-1 KO mice spent significantly more time crossing the beam in the elevated bridge test (A, p<0.05) than wild type mice. DJ-1 KO mice show only 5% recovery from day 2 to days 7 after injury, compared to C57BL/6 mice that improved by 20% over the same period of time. Improvement was also noted in cylinder test 7 days after injury (B). (Data is shown as mean ± SEM).</p

Effect of ND-13 treatment on functional recovery of DJ-1 KO mice after ET-1 induced focal ischemic injury.

<p>DJ-1 KO mice treated with ND-13 show improvement 2 days after ischemic injury in the elevated bridge test as they spend less time crossing the beam than wild type mice (A, p<0.05). This effect was consistent for at least two weeks following injury. Improvement was also noted in cylinder test 7 days after injury (B). (Data is shown as mean ± SEM).</p