Modulation of response times in early-stage Parkinson's disease during emotional processing of embodied and non-embodied stimuli.

Valence (positive and negative) and content (embodied vs non-embodied) characteristics of visual stimuli have been shown to influence motor readiness, as tested with response time paradigms. Both embodiment and emotional processing are affected in Parkinson's disease (PD) due to basal ganglia dysfunction. Here we aimed to investigate, using a two-choice response time paradigm, motor readiness when processing embodied (emotional body language [EBL] and emotional facial expressions [FACS]) vs non-embodied (emotional scenes [IAPS]) stimuli with neutral, happy, and fearful content. We enrolled twenty-five patients with early-stage PD and twenty-five age matched healthy participants. Motor response during emotional processing was assessed by measuring response times (RTs) in a home-based, forced two-choice discrimination task where participants were asked to discriminate the emotional stimulus from the neutral one. Rating of valence and arousal was also performed. A clinical and neuropsychological evaluation was performed on PD patients. Results showed that RTs for PD patients were longer for all conditions compared to HC and that RTs were generally longer in both groups for EBL compared to FACS and IAPS, with the sole exception retrieved for PD, where in discriminating fearful stimuli, RTs for EBL were longer compared to FACS but not to IAPS. Furthermore, in PD only, when discriminating fearful respect to neutral stimuli, RTs were shorter when discriminating FACS compared to IAPS. This study shows that PD patients were faster in discriminating fearful embodied stimuli, allowing us to speculate on mechanisms involving an alternative, compensatory, emotional motor pathway for PD patients undergoing fear processing.

Group-based exercise for Parkinson's: a qualitative study of participants and partners' perceptions of an exercise class delivered through a community-university collaboration.

BACKGROUND: Community-based exercise programmes (CBEPs) offer a practical and viable approach to providing people with Parkinson's disease (PwP) the opportunity to exercise as an ancillary therapeutic benefit to pharmacological management. This study explores the perceptions of exercising participants (PwP) and non-participating partners involved in an exercise class delivered through a community-university partnership. METHODS: Two separate focus group discussions were conducted: one with class participants (PwP: n = 7, H&Y scale I to III), and the other with non-participating partners of PwP (n = 4). RESULTS: Thematic analysis of the data identified that a range of physical, psychological and social factors were perceived to influence engagement: (1) actively taking control, (2) exercise is medicine for the mind and body, and (3) a community working together to promote exercise for parkinson's. Participants and partners felt that the support from the group, including the instructors and student volunteers, empowered and supported PwP to proactively self-manage their health, enjoy exercise in an inclusive group setting, and develop strong social connections with others in the local Parkinson's community. Support to exercise from healthcare professionals was identified as both an enabler and barrier to participation. CONCLUSIONS: This study underscores the significance of a community-university partnership as a complementary therapeutic approach for PwP. It also provides critical reflections on its sustainability, including implications for how exercise is considered as medicine for PwP. Additionally, it offers practical recommendations to galvanise community participation and provide inclusive and viable exercise opportunities for PwP.

Left corticospinal tract could be a biomarker to identify the dual prodromal LRRK2/GBA mutated Parkinson's disease.

INTRODUCTION: Prodromal Parkinson's disease (PD) carriers of dual leucine-rich repeat kinase 2 (LRRK2) and glucosylceramidase ß (GBA) variants are rare, and their biomarkers are less well developed. OBJECTIVE: This study aimed to investigate the biomarkers for diagnosing the prodromal phase of LRRK2-GBA-PD (LRRK2-GBA-prodromal). METHODS: We assessed the clinical and whole-brain white matter microstructural characteristics of 54 prodromal PD carriers of dual LRRK2 (100% M239T) and GBA (95% N409S) variants, along with 76 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort. RESULTS: By analyzing the four values of 100 nodes on 20 fiber bundles, totaling 8000 data points, we identified the smallest p value in the fractional anisotropy (FA) value of the 38th segment of left corticospinal tract (L-CST) with differences between LRRK2-GBA-prodromal and HCs (p = 8.94 × 10-9). The FA value of the 38th node of the L-CST was significantly lower in LRRK2-GBA-prodromal (FA value, 0.65) compared with HCs (FA value, 0.71). The receiver-operating characteristic curve showed a cut-off value of 0.218 for the FA value of L-CST, providing sufficient sensitivity (79.2%) and specificity (72.2%) to distinguish double mutation prodromal PD from the healthy population. CONCLUSION: L-CST, especially the 38th node, may potentially serve as a biomarker for distinguishing individuals with double mutation prodromal PD from the healthy population.

Causal relationship between PCSK9 inhibitor and common neurodegenerative diseases: A drug target Mendelian randomization study.

BACKGROUND: In addition to lowering cholesterol levels, the proprotein convertase subtilis kexin 9 (PCSK9) inhibitor has a variety of effects, including anti-neuroapoptosis. However, the effects of PCSK9 inhibitors on neurodegenerative diseases are controversial. Therefore, we used drug-targeted Mendelian randomization (MR) analysis to investigate the effects of PCSK9 inhibitors on different neurodegenerative diseases. METHODS: We collected single nucleotide polymorphisms (SNPs) of PCSK9 from published statistics of genome-wide association studies and performed drug target MR analyses to detect a causal relationship between PCSK9 inhibitors and the risk of neurodegenerative diseases. We utilized the effects of 3-Hydroxy -3- methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors (statin targets) for comparison with PCSK9 inhibitors. Coronary heart disease risk was used as a positive control, and primary outcomes included amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). RESULTS: PCSK9 inhibitors marginally reduced the risk of ALS (OR [95%] = 0.89 [0.77 to 1.00], p = 0.048), while they increased the risk of PD (OR [95%] = 1.417 [1.178 to 1.657], p = 0.004). However, HMGCR inhibitors increased the risk of PD (OR [95%] = 1.907 [1.502 to 2.312], p = 0.001). CONCLUSION: PCSK9 inhibitors significantly reduce the risk of ALS but increase the risk of PD. HMGCR inhibitors may be the risk factor for PD.

Therapeutic Potential of Recreation on Non-Motor Symptoms in Parkinson's Disease: A Literature Review.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder of the central nervous system. Non-motor symptoms (NMSs) such as anxiety, depression, sleep disorders, autonomic dysregulation, and sensory impairments are as debilitating as motor symptoms and negatively impact an individual's quality of life. While the majority appear in the prodromal stage, a few NMSs, like anxiety and hallucinations can also occur as a side effect of dopaminergic drugs. Physical activity-based recreation has emerged as a newer non-pharmacological approach to managing NMS in PD. However, there is a paucity of literature proving its efficacy in reducing NMS burden. Primary Objective: The objective of the present review is to summarise evidence on the efficacy of physical activity-based recreation to manage NMSs in PD. Methods: A literature search was conducted in PubMed, CINAHL, and Cochrane Library databases. Fifty studies including randomized controlled trials, systematic reviews, and cohort studies published between 2012-2022 were reviewed thoroughly as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Scoping Review (PRISMA-ScR) guidelines. Setting: India. Participants: Individuals with PD. Results: Three out of eight studies, one fair quality (level IIa) and two high-quality studies (level Ib and Ia respectively) observed the effects of dance on NMS, two high-quality studies (level Ib) examined the effects of Tai-chi, two high-quality studies (level Ia and Ib respectively) examined the effect of Qigong while the remaining one high-quality study (level Ia) assessed the effects of Yoga. Conclusion: Review findings indicate that yoga and Tai-chi followed by Qigong and dance are effective therapeutic adjuncts to regular physiotherapy interventions in alleviating NMSs in individuals with PD.

Comment on "Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries".

The 5-2-1 criteria are intended to help general neurologists identify patients with advanced Parkinson's disease who may benefit from treatment optimisation, such as with a device-aided therapy. Although the 5-2-1 criteria claim to address an unmet need, we urge readers to cautiously interpret the results of this validation study.

Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.

Cyclin-dependent kinase 5 (Cdk5) is a protein expressed in postmitotic neurons in the central nervous system (CNS). Cdk5 is activated by p35 and p39 which are neuron regulatory subunits. Cdk5/p35 complex is activated by calpain protease to form Cdk5/p35 which has a neuroprotective effect by regulating the synaptic plasticity and memory functions. However, exaggerated Cdk5 is implicated in different types of neurodegenerative diseases including Parkinson disease (PD). Therefore, modulation of Cdk5 signalling may mitigate PD neuropathology. Therefore, the aim of the present review was to discuss the critical role of Cdk5 in the pathogenesis of PD, and how Cdk5 inhibitors are effectual in the management of PD. In conclusion, overactivated Cdk5 is involved the development of neurodegeneration, and Cdk5/calpain inhibitors such as statins, metformin, fenofibrates and rosiglitazone can attenuate the progression of PD neuropathology.

Cross-Sectional and Longitudinal Association of Clinical and Neurocognitive Factors With Apathy in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: A robust understanding of the natural history of apathy in Parkinson disease (PD) is foundational for developing effective clinical management tools. However, large longitudinal studies are lacking while the literature is inconsistent about even cross-sectional associations. We aimed to determine the longitudinal predictors of apathy development in a large cohort of people with PD and its cross-sectional associations and trajectories over time, using sophisticated Bayesian modeling techniques. METHODS: People with PD followed up in the longitudinal New Zealand Parkinson's progression project were included. Apathy was defined using the neuropsychiatric inventory subscale ≥4, and analyses were also repeated using a less stringent cutoff of ≥1. Both MoCA and comprehensive neuropsychological testing were used as appropriate to the model. Depression was assessed using the hospital anxiety and depression scale. Cross-sectional Bayesian regressions were conducted, and a multistate predictive model was used to identify factors that predict the initial onset of apathy in nonapathetic PD, while also accounting for the competing risk of death. The relationship between apathy presence and mortality was also investigated. RESULTS: Three hundred forty-six people with PD followed up for up to 14 years across a total of 1,392 sessions were included. Apathy occurrence did not vary significantly across the disease course (disease duration odds ratio [OR] = 0.55, [95% CI 0.28-1.12], affecting approximately 11% or 22% of people at any time depending on the NPI cutoff used. Its presence was associated with a significantly higher risk of death after controlling for all other factors (hazard ratio [HR] = 2.92 [1.50-5.66]). Lower cognition, higher depression levels, and greater motor severity predicted apathy development in those without motivational deficits (HR [cognition] = 0.66 [0.48-0.90], HR [depression] = 1.45 [1.04-2.02], HR [motor severity] = 1.37 [1.01-1.86]). Cognition and depression were also associated with apathy cross-sectionally, along with male sex and possibly lower dopaminergic therapy level, but apathy still occurred across the full spectrum of each variable (OR [cognition] = 0.58 [0.44-0.76], OR [depression] = 1.43 [1.04-1.97], OR [female sex] = 0.45 [0.22-0.92], and OR [levodopa equivalent dose] = 0.78 [0.59-1.04]. DISCUSSION: Apathy occurs across the PD time course and is associated with higher mortality. Depressive symptoms and cognitive impairment in particular predict its future development in those with normal motivation.

Brain Targeting Nanomedicines: Pitfalls and Promise.

Brain diseases are the most devastating problem among the world's increasingly aging population, and the number of patients with neurological diseases is expected to increase in the future. Although methods for delivering drugs to the brain have advanced significantly, none of these approaches provide satisfactory results for the treatment of brain diseases. This remains a challenge due to the unique anatomy and physiology of the brain, including tight regulation and limited access of substances across the blood-brain barrier. Nanoparticles are considered an ideal drug delivery system to hard-to-reach organs such as the brain. The development of new drugs and new nanomaterial-based brain treatments has opened various opportunities for scientists to develop brain-specific delivery systems that could improve treatment outcomes for patients with brain disorders such as Alzheimer's disease, Parkinson's disease, stroke and brain tumors. In this review, we discuss noteworthy literature that examines recent developments in brain-targeted nanomedicines used in the treatment of neurological diseases.

Regional Burden of Enlarged Perivascular Spaces and Cognition and Neuropsychiatric Symptoms in Drug-Naive Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population. METHODS: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS). RESULTS: A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS (p for trend <0.001) and BG-EPVS (p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS. DISCUSSION: BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.

DDAH-1 maintains endoplasmic reticulum-mitochondria contacts and protects dopaminergic neurons in Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra is a hallmark of pathology in Parkinson's disease (PD). Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) is the critical enzyme responsible for the degradation of asymmetric dimethylarginine (ADMA) which inhibits nitric oxide (NO) synthase and has been implicated in neurodegeneration. Mitochondrial dysfunction, particularly in the mitochondria-associated endoplasmic reticulum membrane (MAM), plays a critical role in this process, although the specific molecular target has not yet been determined. This study aims to examine the involvement of DDAH-1 in the nigrostriatal dopaminergic pathway and PD pathogenesis. The distribution of DDAH-1 in the brain and its colocalization with dopaminergic neurons were observed. The loss of dopaminergic neurons and aggravated locomotor disability after rotenone (ROT) injection were showed in the DDAH-1 knockout rat. L-arginine (ARG) and NO donors were employed to elucidate the role of NO respectively. In vitro, we investigated the effects of DDAH-1 knockdown or overexpression on cell viability and mitochondrial functions, as well as modulation of ADMA/NO levels using ADMA or ARG. MAM formation was assessed by the Mitofusin2 oligomerization and the mitochondrial ubiquitin ligase (MITOL) phosphorylation. We found that DDAH-1 downregulation resulted in enhanced cell death and mitochondrial dysfunctions, accompanied by elevated ADMA and reduced NO levels. However, the recovered NO level after the ARG supplement failed to exhibit a protective effect on mitochondrial functions and partially restored cell viability. DDAH-1 overexpression prevented ROT toxicity, while ADMA treatment attenuated these protective effects. The declines of MAM formation in ROT-treated cells were exacerbated by DDAH-1 downregulation via reduced MITOL phosphorylation, which was reversed by DDAH-1 overexpression. Together, the abundant expression of DDAH-1 in nigral dopaminergic neurons may exert neuroprotective effects by maintaining MAM formation and mitochondrial function probably via ADMA, indicating the therapeutic potential of targeting DDAH-1 for PD.

Citrobacter rodentium infection impairs dopamine metabolism and exacerbates the pathology of Parkinson's disease in mice.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. Intestinal inflammation involved in the pathogenesis of PD, but the underlying mechanism is not fully understood. Citrobacter rodentium (C.R) is a gram-negative bacterium that can be used to induce human inflammatory bowel disease in mice. Here, we investigated whether the proinflammatory effects caused by C.R infection initiate PD-like injury and/or exacerbate PD pathology and extensively studied the underlying mechanism. Mice were gavaged once with C.R and monitored for several pathological features at 9 days post infection. The results showed that C.R delivery in mice induced IBD-like symptoms, including significant weight loss, increased fecal water content, an impaired intestinal barrier, intestinal hyperpermeability and inflammation, and intestinal microbiota disturbances. Notably, C.R infection modified dopamine (DA) metabolism in the brains of both male and female mice. Subsequently, a single high dose of MPTP or normal saline was administered at 6 days post infection. At 3 days after MPTP administration, the feces were collected for 16 S rRNA analysis, and PD-like phenotypes and mechanisms were systemically analyzed. Compared with C.R or MPTP injection alone, the injection of C.R and MPTP combined worsened behavioral performance. Moreover, such combination triggered more severe dopaminergic degeneration and glial cell overactivation in the nigrostriatal pathway of mice. Mechanistically, the combination of C.R and MPTP increased the expression of TLR4 and NF-κB p65 in the colon and striatum and upregulated proinflammatory cytokine expression. Therefore, C.R infection-induced intestinal inflammation can impair dopamine metabolism and exacerbate PD pathological processes.

Globus pallidus externus drives increase in network-wide alpha power with propofol-induced loss-of-consciousness in humans.

States of consciousness are likely mediated by multiple parallel yet interacting cortico-subcortical recurrent networks. Although the mesocircuit model has implicated the pallidocortical circuit as one such network, this circuit has not been extensively evaluated to identify network-level electrophysiological changes related to loss of consciousness (LOC). We characterize changes in the mesocircuit in awake versus propofol-induced LOC in humans by directly simultaneously recording from sensorimotor cortices (S1/M1) and globus pallidus interna and externa (GPi/GPe) in 12 patients with Parkinson disease undergoing deep brain stimulator implantation. Propofol-induced LOC is associated with increases in local power up to 20 Hz in GPi, 35 Hz in GPe, and 100 Hz in S1/M1. LOC is likewise marked by increased pallidocortical alpha synchrony across all nodes, with increased alpha/low beta Granger causal (GC) flow from GPe to all other nodes. In contrast, LOC is associated with decreased network-wide beta coupling and beta GC from M1 to the rest of the network. Results implicate an important and possibly central role of GPe in mediating LOC-related increases in alpha power, supporting a significant role of the GPe in modulating cortico-subcortical circuits for consciousness. Simultaneous LOC-related suppression of beta synchrony highlights that distinct oscillatory frequencies act independently, conveying unique network activity.

Hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice.

Depression is a common non-motor symptom of Parkinson's disease. Previous studies demonstrated that hydroxysafflor yellow A had properties of improving motor symptoms of Parkinson's disease. The effect of hydroxysafflor yellow A on depression in Parkinson's disease mice is investigated in this study. To induce Parkinson's disease model, male Swiss mice were exposed to rotenone (30 mg/kg) for 6 weeks. The chronic unpredictable mild stress was employed to induce depression from week 3 to week 6. Sucrose preference, tail suspension, and forced swimming tests were conducted. Golgi and Nissl staining of hippocampus were carried out. The levels of dopamine, 5-hydroxytryptamine and the expression of postsynaptic density protein 95, brain-derived neurotrophic factor in hippocampus were assayed. It showed that HSYA improved the depression-like behaviors of Parkinson's disease mice. Hydroxysafflor yellow A attenuated the injury of nerve and elevated contents of dopamine, 5-hydroxytryptamine in hippocampus. Treatment with hydroxysafflor yellow A also augmented the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor. These findings suggest that hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice through regulating the contents of postsynaptic density protein 95 and brain-derived neurotrophic factor, therefore protecting neurons and neuronal dendrites of the hippocampus.

A comparison of quantitative parameters of axial posture and spinal mobility between motor subtypes of Parkinson's disease.

Background and purpose:

Parkinson’s disease (PD) is a heterogeneous neurodegenerative disorder characterized by contradictory clinical outcomes among its several subtypes. The disease can manifest with a tremor-dominant (TD) or a non-tremor-dominant (NTD) phenotype. Although the TD subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of axial symptoms. For this reason, in this study it was aimed to make a quantitative comparison of axial posture and spinal mobility between PD with TD and NTD. 

This case-control study was conducted on 94 patients with diagnosed PD. A group diagnosis approach was used in the study, such that the diagnosis of each patient was confirmed, and they were assig-ned to TD and NTD groups by a neurologist expert on movement disorders. Of the patients with PD, 61 were in the TD group, and 33 were in the NTD group. Spinal mouse was used to measure spinal posture and spinal mobility in both sagittal and frontal planes. 

Two groups of 61 patients (25 male + 36 female) with TD-PD (mean age: 64.49±10.37 years) and 33 patients (20 male +13 female) with NTD-PD (mean age: 63.45±9.11 years) were enrolled in the study. There were no significant differences bet­ween the patients with TD and NTD in terms of sagittal and frontal postures (p>0.05). In addition to this, anterior trunk tilt was found to significantly increase as the disease stage advanced in both groups. While the greatest anterior trunk tilt change in the TD-PD group was observed in the 3rd stage, NTD-PD group was in the 2.5th stage. Aside from this, the out­comes of the spinal mobility measurements in the frontal and sagittal planes were similar between the groups (p>0.05).

It is widely acknowledged that many clinical aspects of the TD and NTD forms of PD differ; however, in our study, it was observed that there may be no difference in the axial symptoms of the patients with PD in terms of classification according to tremor dominance.

Study on the relationship between peripheral nerve fiber types and levodopa usage in Parkinson's disease.

Background and purpose:

The aim of this study is to comprehensively determine the types of affected fibers in Parkinson’s disease (PD) patients by employing nerve conduction studies (NCS), sympathetic skin response (SSR) examinations, and current perception threshold (CPT) testing and to analyze the correlation between levodopa use and nerve involvement.

This retrospective study included 36 clinically diagnosed PD patients who were recruited between January 2018 and April 2019. All patients underwent NCS, SSR testing, and CPT sensory examinations. Additionally, the PD patients were assessed for disease staging using the Hoehn and Yahr (H-Y) scale. 

Fifteen patients were included in the tremor-dominant subtype, ten patients in the rigid-dominant subtype, and eleven patients in the mixed subtype. Eleven patients were using levodopa, while twenty-five patients had never used any anti-Parkinson’s medication. Ten patients (28%) showed abnormal sympathetic skin responses (SSR). The CPT examination revealed sensory abnormalities in twenty-four patients (67%), with eighteen patients (75%) experiencing sensory hypersensitivity and six patients (25%) experiencing sensory hypoesthesia. Twelve patients (33%) had normal CPT results. Among the patients with abnormal CPT findings, seven cases (29%) involved large myelinated fiber damage, twenty-two cases (92%) involved small myelinated fiber damage, and nineteen cases (79%) involved unmyelinated fiber damage. The rate of sensory abnormalities was 64% (7/11) in the levodopa group and 68% (17/25) in the non-levodopa group, with no statistically significant difference between the two groups. 

The incidence of abnormal CPT findings in PD patients was higher than that of abnormal SSR responses, suggesting that nerve fiber damage primarily affects small fiber nerves (SFN).

Short-term effects of Pilates-based exercise on upper limb strength and function in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have impaired upper limb motor coordination, limiting the execution of activities of daily living. This study investigated the feasibility and safety of a short-term Pilates-based exercise program in the treatment of upper limb motor coordination for people with PD. METHODS: Fifteen patients - n (%) 4 women/11 men (27/73), median [interquartile range] age 66 [9] years - participated in this quasi-experimental (before-and-after) clinical trial. Patients underwent a 6-week (30 min/day, 3 days/week) Pilates exercise program using Reformer, Cadillac, Chair, and Barrel equipment. Feasibility was evaluated by adherence to the program and the ability to perform the exercises including progressions on difficulty. Safety was evaluated based on self-reported adverse events. Clinical and functional trends before and after the intervention were also computed regarding handgrip strength (HGS), fine motor coordination (9 Hole Peg Test; 9HPT), bradykinesia (Movement Disorder Society - Unified Parkinson's disease Rating Scale; MDS-UPDRS), and upper limb functionality (Test D'évaluation des Membres Supérieurs des Personnes Âgées, TEMPA). RESULTS: Of the 18 Pilates sessions, exercise adherence was 100%. The only adverse event observed was mild muscle pain. Pre-post differences were observed only for body bradykinesia and hypokinesia (1.0 [0.0] vs. 0.0 [1.0] s, adjusted p = 0.048). CONCLUSIONS: A short-term Pilates-based exercise program in the treatment of upper limb muscle strength, manual dexterity, bradykinesia, and functionality is feasible and safe for people with PD. Changes in upper limb bradykinesia encourage randomized clinical trials.

The effect of a home-based exercise program on gait characteristics in an individual with Parkinson's disease over a one-year period: A case study.

BACKGROUND: The COVID-19 pandemic has placed a restriction on physiotherapy clinical visits for supervised exercise. It is important that individuals with Parkinson's Disease (PD) continue an exercise regime at home during the pandemic and also in normal situations. OBJECTIVE: The purpose of this study was to explore the case history of an individual with PD who used a developed home-based exercise programme for one year during the COVID-19 pandemic. METHODS: A 67 year-old married woman was diagnosed with PD stage 2.5 on the modified Hoehn and Yahr (HY) scale. Gait characteristics and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor scores were assessed at baseline, 10 weeks, and 12 months. The home-based exercise program included breathing exercises, posture correction, stretching exercises, rotation of the axial segments, balance training, and task-specific gait training. RESULTS: After 12 months, her MDS-UPDRS motor scores decreased when compared to baseline and 10 weeks, and gait characteristics at 12 months showed an increase in the degree of foot rotation, step length, cadence, and gait speed when compared to baseline and 10 weeks. CONCLUSION: This case study showed that improvements in MDS-UPDRS and gait characteristics can continue over a 12 month period as a result of a home-based exercise programme. Therefore, home-based exercise programs should be encouraged with weekly monitoring, especially in individuals with gait disorders which show deterioration.

Discovery of novel benzimidazole derivatives as selective and reversible monoamine oxidase B inhibitors for Parkinson's disease treatment.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The development of novel scaffolds for human monoamine oxidase B (hMAO-B) inhibitors with reversible properties represents an important strategy to improve the efficacy and safety for PD treatment. In the current work, we have devised and assessed two innovative derivative series serving as hMAO-B inhibitors. These series have utilized benzimidazole as a scaffold and strategically incorporated a primary amide group, which is recognized as a pivotal pharmacophore in subsequent activity screening and reversible mode of action. Among these compounds, 16d has emerged as the most potent hMAO-B inhibitor with an IC50 value of 67.3 nM, comparable to safinamide (IC50 = 42.6 nM) in vitro. Besides, 16d demonstrated good selectivity towards hMAO-B isoenzyme with a selectivity index over 387. Importantly, in line with the design purpose, 16d inhibited hMAO-B in a competitive and reversible manner (Ki = 82.50 nM). Moreover, 16d exhibited a good safety profile in both cellular and acute toxicity assays in mice. It also displayed ideal pharmacokinetic properties and blood-brain barrier permeability in vivo, essential prerequisites for central nervous system medicines. In the MPTP-induced PD mouse model, 16d significantly alleviated the motor impairment, especially muscle relaxation and motor coordination. Therefore, 16d, serving as a lead compound, holds instructive significance for subsequent investigations regarding its application in the treatment of PD.