An 8-week aerobic cycling intervention elicits improved gait velocity and biomechanics in persons with Parkinson’s disease

BackgroundIt is unknown if improvements in gait velocity following an aerobic cycling intervention are accompanied by improved gait biomechanics in individuals with Parkinson’s disease (PD) or if gait abnormalities are exaggerated in response to increased velocity.Research questionCan an 8-week aerobic cycling intervention elicit improvements in locomotor function in individuals with mild to moderate PD?MethodsA secondary analysis of data from a randomized clinical trial was conducted in individuals with mild to moderate idiopathic PD (N = 28). Participants were randomized to an aerobic cycling intervention (PD_ex, N = 14) consisting of 24 sessions at a targeted aerobic intensity of 60–80% of heart rate reserve or to a no intervention control group (PD_control, N = 14). Change in comfortable walking speed in addition to gait kinematics, kinetics, and spatiotemporal variables using motion capture were obtained at baseline and end of treatment (EOT).ResultsThe PD_ex group made significantly greater improvements in the primary outcome, change in comfortable gait velocity, from 0.86 ± 0.24 m/s at baseline to 1.00 ± 0.23 m/s at EOT compared to the PD_control group who declined from 0.91 ± 0.23 m/s at baseline to 0.80 ± 0.29 at EOT (P = 0.002). Improvements in gait velocity for the PD_ex group were accompanied by improvements in gait kinematics, kinetics, and spatiotemporal parameters, while the PD_control group demonstrated slight worsening in all gait parameters over the 8-week period.SignificanceThe 8-week moderate- to high-intensity cycling intervention elicited significantly greater improvements in gait velocity compared to the PD_control group. Increased gait velocity was accompanied by normalization of gait biomechanics, rather than an exaggeration of existing gait deviations. Aerobic cycling may be a viable treatment approach to improve gait velocity and gait biomechanics in individuals with mild to moderate PD and may mitigate declines in mobility.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Brain lipidomics as a rising field in neurodegenerative contexts: Perspectives with Machine Learning approaches

Lipids are essential for cellular functioning considering their role in membrane composition, signaling, and energy metabolism. The brain is the second most abundant organ in terms of lipid concentration and diversity only after adipose tissue. However, in the central system (CNS) lipid dysregulation has been linked to the etiology, progression, and severity of neurodegenerative diseases such as Alzheimeŕs, Parkinson, and Multiple Sclerosis. Advances in the human genome and subsequent sequencing technologies allowed us the study of lipidomics as a promising approach to diagnosis and treatment of neurodegeneration. Lipidomics advances rapidly increased the amount and quality of data allowing the integration with other omic types as well as implementing novel bioinformatic and quantitative tools such as machine learning (ML). Integration of lipidomics data with ML, as a powerful quantitative predictive approach, led to improvements in diagnostic biomarker prediction, clinical data integration, network, and systems approaches for neural behavior, novel etiology markers for inflammation, and neurodegeneration progression and even Mass Spectrometry image analysis. In this sense, by exploiting lipidomics data with ML is possible to improve the identification of new biomarkers or unveil new molecular mechanisms associated with lipid impairment across neurodegeneration. In this review, we present the lipidomic neurobiology state-of-the-art highlighting its potential applications to study neurodegenerative conditions. Also, we present theoretical background, applications, and advances in the integration of lipidomics with ML. This review opens the door to new approaches in this rising field.     

The effectiveness of specialized nursing interventions for patients with Parkinson disease: A randomized controlled study protocol

Background:The purpose of this experiment is to evaluate the impact of the care of Parkinson disease nurse specialist on improving motor symptoms and life quality for patients with Parkinson disease (PD).Method:This is a randomized controlled research, and it will be conducted from April 2021 to October 2021 at Sichuan Provincial People''s Hospital. The experiment was granted through the Research Ethics Committee of Sichuan Provincial People''s Hospital (004510293). All the patients suffer from PD, age 18 years or older, both female and male, regardless of the duration or severity of this disease are eligible. The exclusion criteria contains: lack sufficient knowledge to complete questionnaires, serious physical comorbidities or refuse to take part in the program. In our experiment, the major result measures are motor symptoms and life quality. For the measurement of life quality, we will utilize Parkinson disease Questionnaire-39, the most extensively utilized the scale of life quality in PD. The evaluation of motor symptoms severity is carried out with the revision of Unified Parkinson Disease Rating Scale sponsored by Movement Disorder Society.Results:Table 1 indicates clinical outcomes at different time points.Conclusion:The Parkinson''s disease nurse specialist care may promote the life quality in the PD patients.Trial registration number:researchregistry 6284.     

A review of dementia,focusing on the distinct roles of viral protein corona and MMP9 in dementia: Potential pharmacotherapeutic priorities

Dementia, in particular, is a defining feature of Alzheimer's and Parkinson's diseases. Because of the combination of motor and cognitive impairments, Parkinson's disease dementia (PDD) has a greater impact on affected people than Alzheimer's disease dementia (ADD) and others. If one family member develops dementia, the other members will suffer greatly in terms of social and occupational functioning. Currently, no relevant treatment is available based on an examination of the absolute pathophysiology of dementia. As a result, our objective of current review encouraged to look for dementia pharmacotherapy based on their pathogenesis. We systematically searched electronic databases such as PubMed, Scopus, and ESCI for information on the pathophysiology of demetia, as well as their treatment with allopathic and herbal medications. By modulating intermediate proteins, oxidative stress, viral protein corona, and MMP9 are etiological factors that cause dementia. The pathophysiology of ADD was described by two hypotheses: the amyloid cascade hypothesis and the tau and tangle hypothesis. ADD is caused by an increase in amyloid-beta (Aβ) and neurofibrillary tangles in the cerebrum. The viral protein corona (VPC) is more contagious and helps to form amyloid-beta (Aβ) plaques and neurofibrillary tangles in the cerebrum. Thioredoxin interacting protein (TXNIP) inside the BBB encourages Aβ to become more engaged. PDD is caused by decreased or absent dopamine secretion from nerve cells in the substantia nigra, as well as PRKN gene deletion/duplication mutations, and shift in the PRKN-PACRG organisation, all of which are linked to ageing. This article discussed the pathophysiology of dementia, as well as a list of herbal medications that can easily cross the BBB and have a therapeutic effect on dementia.     

Machine learning models for Parkinson’s disease detection and stage classification based on spatial-temporal gait parameters

BackgroundParkinson’s disease (PD) is a chronic and progressive neurodegenerative disease with no cure, presenting a challenging diagnosis and management. However, despite a significant number of criteria and guidelines have been proposed to improve the diagnosis of PD and to determine the PD stage, the gold standard for diagnosis and symptoms monitoring of PD is still mainly based on clinical evaluation, which includes several subjective factors. The use of machine learning (ML) algorithms in spatial-temporal gait parameters is an interesting advance with easy interpretation and objective factors that may assist in PD diagnostic and follow up.Research questionThis article studies ML algorithms for: i) distinguish people with PD vs. matched-healthy individuals; and ii) to discriminate PD stages, based on selected spatial-temporal parameters, including variability and asymmetry.MethodsGait data acquired from 63 people with PD with different levels of PD motor symptoms severity, and 63 matched-control group individuals, during self-selected walking speed, was study in the experiments.ResultsIn the PD diagnosis, a classification accuracy of 84.6 %, with a precision of 0.923 and a recall of 0.800, was achieved by the Naïve Bayes algorithm. We found four significant gait features in PD diagnosis: step length, velocity and width, and step width variability. As to the PD stage identification, the Random Forest outperformed the other studied ML algorithms, by reaching an Area Under the ROC curve of 0.786. We found two relevant gait features in identifying the PD stage: stride width variability and step double support time variability.SignificanceThe results showed that the studied ML algorithms have potential both to PD diagnosis and stage identification by analysing gait parameters.     

Protective mechanism of Wnt4 gene on Parkinson’s disease (PD) transgenic Drosophila

Objective: The main pathological change of Parkinson’s disease (PD) is progressive degeneration and necrosis of dopaminergic neurons in the midbrain, forming a Lewy body in many of the remaining neurons. Studies have found that in transgenic Drosophila, mutations in the PTEN-inducible kinase 1 (PINK1) gene may cause indirect flight muscle defects in Drosophila, and mitochondrial structural dysfunction as well.

Methods: In this study, Wnt4 gene overexpression and knockdown were performed in PINK1 mutant PD transgenic Drosophila, and the protective effect of Wnt4 gene on PD transgenic Drosophila and its possible mechanism were explored. The Wnt4 gene was screened in the previous experiment; And by using the PD transgenic Drosophila model of the MHC-Gal4/UAS system, the PINK1 gene could be specifically activated in the Drosophila muscle tissue.

Results: In PINK1 mutation transgenic fruit flies, the Wnt4 gene to study its implication on PD transgenic fruit flies’ wing normality and flight ability. We found that overexpression of Wnt4 gene significantly reduced abnormality rate of PD transgenic Drosophila and improved its flight ability, and then, increased ATP concentration, enhanced mitochondrial membrane potential and normalized mitochondrial morphology were found. All of these findings suggested Wnt4 gene may have a protective effect on PD transgenic fruit flies. Furthermore, in Wnt4 gene overexpression PD transgenic Drosophila, down-regulation autophagy and apoptosis-related proteins Ref(2)P, Pro-Caspase3, and up-regulation of Beclin1, Atg8a, Bcl2 protein were confirmed by Western Blotting.

Conclusion: The results imply that the restoring of mitochondrial function though Wnt4 gene overexpression in the PINK1 mutant transgenic Drosophila may be related to autophagy and/or apoptosis.     

Electrophysiological differences between upper and lower limb movements in the human subthalamic nucleus

ObjectiveFunctional processes in the brain are segregated in both the spatial and spectral domain. Motivated by findings reported at the cortical level in healthy participants we test the hypothesis in the basal ganglia of Parkinson’s disease patients that lower frequency beta band activity relates to motor circuits associated with the upper limb and higher beta frequencies with lower limb movements.MethodsWe recorded local field potentials (LFPs) from the subthalamic nucleus using segmented “directional” DBS leads, during which patients performed repetitive upper and lower limb movements. Movement-related spectral changes in the beta and gamma frequency-ranges and their spatial distributions were compared between limbs.ResultsWe found that the beta desynchronization during leg movements is characterised by a strikingly greater involvement of higher beta frequencies (24–31 Hz), regardless of whether this was contralateral or ipsilateral to the limb moved. The spatial distribution of limb-specific movement-related changes was evident at higher gamma frequencies.ConclusionLimb processing in the basal ganglia is differentially organised in the spectral and spatial domain and can be captured by directional DBS leads.SignificanceThese findings may help to refine the use of the subthalamic LFPs as a control signal for adaptive DBS and neuroprosthetic devices.