Artificial Intelligence Applications for Assessment, Monitoring, and Management of Parkinson Disease Symptoms: Protocol for a Systematic Review

\ua9 2023 The authors.Background: Parkinson disease (PD) is the second most prevalent neurodegenerative disease, with around 10 million people with PD worldwide. Current assessments of PD symptoms are conducted by questionnaires and clinician assessments and have many limitations, including unreliable reporting of symptoms, little autonomy for patients over their disease management, and standard clinical review intervals regardless of disease status or clinical need. To address these limitations, digital technologies including wearable sensors, smartphone apps, and artificial intelligence (AI) methods have been implemented for this population. Many reviews have explored the use of AI in the diagnosis of PD and management of specific symptoms; however, there is limited research on the application of AI to the monitoring and management of the range of PD symptoms. A comprehensive review of the application of AI methods is necessary to address the gap of high-quality reviews and highlight the developments of the use of AI within PD care. Objective: The purpose of this protocol is to guide a systematic review to identify and summarize the current applications of AI applied to the assessment, monitoring, and management of PD symptoms. Methods: This review protocol was structured using the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) and the Population, Intervention, Comparator, Outcome, and Study (PICOS) frameworks. The following 5 databases will be systematically searched: PubMed, IEEE Xplore, Institute for Scientific Information’s Web of Science, Scopus, and the Cochrane Library. Title and abstract screening, full-text review, and data extraction will be conducted by 2 independent reviewers. Data will be extracted into a predetermined form, and any disagreements in screening or extraction will be discussed. Risk of bias will be assessed using the Cochrane Collaboration Risk of Bias 2 tool for randomized trials and the Mixed Methods Appraisal Tool for nonrandomized trials. Results: As of April 2023, this systematic review has not yet been started. It is expected to begin in May 2023, with the aim to complete by September 2023. Conclusions: The systematic review subsequently conducted as a product of this protocol will provide an overview of the AI methods being used for the assessment, monitoring, and management of PD symptoms. This will identify areas for further research in which AI methods can be applied to the assessment or management of PD symptoms and could support the future implementation of AI-based tools for the effective management of PD

Parkinson Symptoms and Health Related Quality of Life as Predictors of Costs: A Longitudinal Observational Study with Linear Mixed Model Analysis

OBJECTIVE: To estimate the magnitude in which Parkinson's disease (PD) symptoms and health- related quality of life (HRQoL) determined PD costs over a 4-year period. MATERIALS AND METHODS: Data collected during 3-month, each year, for 4 years, from the ELEP study, included sociodemographic, clinical and use of resources information. Costs were calculated yearly, as mean 3-month costs/patient and updated to Spanish €, 2012. Mixed linear models were performed to analyze total, direct and indirect costs based on symptoms and HRQoL. RESULTS: One-hundred and seventy four patients were included. Mean (SD) age: 63 (11) years, mean (SD) disease duration: 8 (6) years. Ninety-three percent were HY I, II or III (mild or moderate disease). Forty-nine percent remained in the same stage during the study period. Clinical evaluation and HRQoL scales showed relatively slight changes over time, demonstrating a stable group overall. Mean (SD) PD total costs augmented 92.5%, from € 2,082.17 (€ 2,889.86) in year 1 to € 4,008.6 (€ 7,757.35) in year 4. Total, direct and indirect cost incremented 45.96%, 35.63%, and 69.69% for mild disease, respectively, whereas increased 166.52% for total, 55.68% for direct and 347.85% for indirect cost in patients with moderate PD. For severe patients, cost remained almost the same throughout the study. For each additional point in the SCOPA-Motor scale total costs increased € 75.72 (p = 0.0174); for each additional point on SCOPA-Motor and the SCOPA-COG, direct costs incremented € 49.21 (p = 0.0094) and € 44.81 (p = 0.0404), respectively; and for each extra point on the pain scale, indirect costs increased € 16.31 (p = 0.0228). CONCLUSIONS: PD is an expensive disease in Spain. Disease progression and severity as well as motor and cognitive dysfunctions are major drivers of costs increments. Therapeutic measures aimed at controlling progression and symptoms could help contain disease expenses.Abbvie Pharmaceuticals has solely funded the publication of this study; however, the funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Exploring the effects of spinal cord stimulation for freezing of gait in parkinsonian patients

Dopaminergic replacement therapies (e.g. levodopa) provide limited to no response for axial motor symptoms including gait dysfunction and freezing of gait (FOG) in Parkinson’s disease (PD) and Richardson’s syndrome progressive supranuclear palsy (PSP-RS) patients. Dopaminergic-resistant FOG may be a sensorimotor processing issue that does not involve basal ganglia (nigrostriatal) impairment. Recent studies suggest that spinal cord stimulation (SCS) has positive yet variable effects for dopaminergic-resistant gait and FOG in parkinsonian patients. Further studies investigating the mechanism of SCS, optimal stimulation parameters, and longevity of effects for alleviating FOG are warranted. The hypothesis of the research described in this thesis is that mid-thoracic, dorsal SCS effectively reduces FOG by modulating the sensory processing system in gait and may have a dopaminergic effect in individuals with FOG. The primary objective was to understand the relationship between FOG reduction, improvements in upper limb visual-motor performance, modulation of cortical activity and striatal dopaminergic innervation in 7 PD participants. FOG reduction was associated with changes in upper limb reaction time, speed and accuracy measured using robotic target reaching choice tasks. Modulation of resting-state, sensorimotor cortical activity, recorded using electroencephalography, was significantly associated with FOG reduction while participants were OFF-levodopa. Thus, SCS may alleviate FOG by modulating cortical activity associated with motor planning and sensory perception. Changes to striatal dopaminergic innervation, measured using a dopamine transporter marker, were associated with visual-motor performance improvements. Axial and appendicular motor features may be mediated by non-dopaminergic and dopaminergic pathways, respectively. The secondary objective was to demonstrate the short- and long-term effects of SCS for alleviating dopaminergic-resistant FOG and gait dysfunction in 5 PD and 3 PSP-RS participants without back/leg pain. SCS programming was individualized based on which setting best improved gait and/or FOG responses per participant using objective gait analysis. Significant improvements in stride velocity, step length and reduced FOG frequency were observed in all PD participants with up to 3-years of SCS. Similar gait and FOG improvements were observed in all PSP-RS participants up to 6-months. SCS is a promising therapeutic option for parkinsonian patients with FOG by possibly influencing cortical and subcortical structures involved in locomotion physiology

Effects of Music Training on Cortical Plasticity: : Cognitive Rehabilitation of Patients with Traumatic Brain Injury

The aim of this thesis was to explore the neuroplastic effects of playing the piano on patients with cognitive impairment following a mild traumatic brain injury (mTBI). It was hypothesised that playing the piano would stimulate neural networks to re-route neural connections and link up cortical circuits that had been functionally inhibited due to minor disruption of brain tissue. The objective of the intervention was to restore the patients’ cognitive processing to pre-injury levels. The study was designed as a pilot study with three experimental groups: (1) 7 patients with cognitive deficits following mTBI two years post-injury (Group 1), (2) 11 healthy subjects (Group 2), and (3) 12 further healthy subjects (Group 3). A between-group design and a longitudinal (pre-post-intervention) within-subject design were applied. Groups 1 and 2 were given eight weeks of piano training. A combination of cognitive and functional neuroimaging (task-based and resting-state fMRI) in addition to neuropsychological tests were performed pre- and post-intervention for all three groups. The results concurrently demonstrated in two independent analyses and fMRI datasets that longitudinal changes in functional connectivity took place within the orbitofrontal cortex (OFC) in the mTBI patient group only, showing increased connectivity between the OFC regions post-intervention involved in executive functions (EF), social cognition and emotional regulation. This finding provides support for the contribution of the OFC as a key mechanism that potentially drives the cognitive benefit of piano training in TBI, and further suggests a network of other connected frontal regions that may be linked to this. The key findings of this study could suggest a causal relationship between musical training and a functional reorganisation of neural networks that promotes enhanced cognitive performance. These results might hold promise as regards adding a novel music-based intervention to the cognitive rehabilitation of mTBI patients.Doktorgradsavhandlin

Mitochondrial dysfunction, protein misfolding and neuroinflammation in parkinson’s disease: Roads to biomarker discovery

Parkinson’s Disease (PD) is a highly prevalent neurodegenerative disease among older adults. PD neuropathology is marked by the progressive loss of the dopaminergic neurons of the substantia nigra pars compacta and the widespread accumulation of misfolded intracellular α-synuclein (α-syn). Genetic mutations and post-translational modifications, such as α-syn phos-phorylation, have been identified among the multiple factors supporting α-syn accrual during PD. A decline in the clearance capacity of the ubiquitin-proteasome and the autophagy-lysosomal systems, together with mitochondrial dysfunction, have been indicated as major pathophysiological mechanisms of PD neurodegeneration. The accrual of misfolded α-syn aggregates into soluble oligomers, and the generation of insoluble fibrils composing the core of intraneuronal Lewy bodies and Lewy neurites observed during PD neurodegeneration, are ignited by the overproduction of reactive oxygen species (ROS). The ROS activate the α-syn aggregation cascade and, together with the Lewy bodies, promote neurodegeneration. However, the molecular pathways underlying the dynamic evolution of PD remain undeciphered. These gaps in knowledge, together with the clinical heterogeneity of PD, have hampered the identification of the biomarkers that may be used to assist in diagnosis, treatment monitoring, and prognostication. Herein, we illustrate the main pathways involved in PD pathogenesis and discuss their possible exploitation for biomarker discovery