Parkinsonian Motor Research Articles

Attenuated afferent inhibition correlated with impaired gait performance in Parkinson’s disease patients with freezing of gait

BackgroundThe neural mechanisms underlying freezing of gait (FOG) in Parkinson’s disease (PD) have not been completely comprehended. Sensory-motor integration dysfunction was proposed as one of the contributing factors. Here, we investigated short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI), and analyzed their association with gait performance in FOG PD patients, to further validate the role of sensorimotor integration in the occurrence of FOG in PD.MethodsTwenty-five levodopa responsive-FOG PD patients (LR-FOG), fifteen levodopa unresponsive-FOG PD patients (LUR-FOG), twenty-eight PD patients without FOG (NO-FOG PD) and twenty-two healthy controls (HC) were included in the study. Clinical features such as PD motor symptoms, FOG severity and cognitive abilities were evaluated using clinical scales in subjects with PD. All participants underwent paired associative stimulation (PAS) to evaluate SAI and LAI in addition to regular input-output curve by transcranial magnetic stimulation. The performances of gait were assessed using a portable gait analyzing system in 10-meter timed Up and Go task. The correlations between the gait spatiotemporal parameters or the scores of FOG scale and the magnitudes of SAI or LAI were analyzed.ResultsCompared to HC and NO-FOG PD patients, SAI was decreased in FOG PD subgroups. LAI was also reduced in both LR-FOG PD and LUR-FOG PD in relative to HC; however, only LUR-FOG PD showed significant reduction of LAI in comparison to NO-FOG PD group. FOG PD patients showed poorer gait performance compared to HC and NO-FOG PD group. The reduction of SAI and LAI were correlated with the impaired gait spatiotemporal parameters or scores of FOG scale in PD with FOG.ConclusionThe SAI and LAI were attenuated in PD patients with FOG, and the reduction of SAI or LAI were correlated to disturbed gait performance, indicating that sensory-motor integration dysfunction played a role in the development of FOG in PD.

Pathophysiology of Motor Control Abnormalities in Parkinson's Disease.

Research in the last few decades has brought us closer to an understanding of the brain circuit abnormalities that underlie parkinsonian motor signs. This article summarizes the current knowledge in this rapidly emerging field. Traditional observations of activity changes of basal ganglia neurons that accompany akinesia and bradykinesia have been supplemented with new knowledge regarding specific pathophysiologic changes that are associated with other parkinsonian signs, such as tremor and gait impairments. New research also emphasizes the role of non-basal ganglia structures in parkinsonism, including the pedunculopontine nucleus, the cerebellum, and the cerebral cortex, and the role of structural and functional neuroplasticity. A more detailed understanding of the brain network abnormalities that result from Parkinson's disease is necessary to arrive at more effective and specific treatments for these symptoms in parkinsonian patients through circuit interventions reaching from deep brain stimulation to genetic and chemogenetic treatments.

Bacopaside-I ameliorates motor dysfunction and neurodegeneration in rat model of Parkinson's disease.

Chronic administration of Bacopa monnieri extract exerts neuroprotective potential in multiple animal models of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), depression, and other cognitive impairments. However, the underlying mechanism of action remained unclear. Rotenone model of PD holds a great potential for investigating PD pathology and motor and nonmotor symptoms. Herein, we evaluated the neuroprotective effect of Bacopaside-I (BS-I), a major triterpenoid saponin of Bacopa monnieri extract, against rotenone-induced in vivo model of PD and explored the possible molecular mechanism. Rats were exposed to rotenone (2mg/kg body weight) for a period of 4 consecutive weeks to induce PD-like behavior. BS-I (5, 15, and 45mg/kg) was administered orally. Behavioral data (rotarod, foot printing, and grip strength test) suggest that BS-I plays a significant role in attenuating the motor function deficit. Exposure to rotenone reduces the dopamine level and increases oxidative stress, while BS-I treatment reversed these changes. Furthermore, chronic administration of BS-I increased the expression levels of dopamine transporter (DAT) and vesicular monoamine transporter (VMAT) genes and the numbers of tyrosine hydroxylase (TH)-positive neurons as compared to rotenone-exposed animals. Our study established the neuroprotective role of BS-I in PD model and laid the foundation for further evaluation of BS-I-based drug in future studies.

Pharmacological targeting of dopamine D1 or D2 receptors evokes a rapid-onset parkinsonian motor phenotype in mice.

Dopaminergic nigrostriatal denervation in Parkinson's disease (PD) disrupts the functional balance between striatal projecting neurons, leading to aberrant activity in the cortico-basal ganglia circuit and characteristic motor symptoms. While genetic and toxin-based animal models are commonly used to mimic PD pathology and behaviour, they have limitations when combined with circuit manipulation tools. This highlights the need for complementary approaches, particularly when combined with viral-based circuit targeting of specific neuronal subpopulations involved in PD circuit dysfunction. Here, we pursue a pharmacological approach targeting dopamine D1 or D2 receptors to induce dopamine deprivation and to replicate key motor symptoms in PD. We demonstrate a clear dose-dependent induction of parkinsonian motor behaviour by both a dopamine D1 receptor antagonist (SCH23390) and a D2 receptor antagonist (haloperidol). The motor phenotype is evaluated by considering relevant motor metrics in an open-field maze platform. The proposed parkinsonian pharmacological model constitutes an acute, flexible approach, which allows parallel brain circuit manipulations.

Histaminergic Innervation of the Ventral Anterior Thalamic Nucleus Alleviates Motor Deficits in a 6-OHDA-Induced Rat Model of Parkinson’s Disease

AbstractThe ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K+ channels, or Ca2+-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.

GLP‐1 receptor agonists for Parkinson's disease: An updated meta-analysis

IntroductionTreatments for Parkinson's disease (PD) focus on symptom reduction through dopaminergic therapies, without clear evidence of disease-modifying effects. Glucagon-like peptide-1 (GLP-1) receptor agonists may reduce neuroinflammation by decreasing microglia activation in PD. Clinical trials suggest these agents have disease-modifying potential in PD. ObjectiveEvaluate the efficacy of GLP-1 receptor agonists in PD. MethodsPubMed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs) of GLP-1 agonists for PD, up to July 2024. The risk of bias was assessed using the RoB-2 tool, and statistical analysis was performed with RevMan 5.4.1 software. ResultsGLP-1 receptor agonists showed a beneficial effect on MDS-UPDRS part III motor scores compared to placebo. Off-medication state, there was a −1.22 point improvement (95%CI -2.46, 0.22; P = 0.05). On-medication state, scores improved by −2.52 points (95%CI -4.02, −1.01; P = 0.001). The global MDS-UPDRS score showed a −3.43-point difference (95%CI -6.48, −0.48; P = 0.02). Cognitive performance, assessed via the Mattis DRS-2, improved by 1.32 points (95%CI 0.16, 2.52; P = 0.03). There were no significant differences in the NMSS (−0,19; 95%IC -3,44, 3,05; P = 0.91), in MADRS (−1,04; 95%IC -2,57, 0,48; P = 0.18), or PDQ-39 (−0,91; 95%IC -2,22, 0,39; P = 0.17). ConclusionGLP-1 receptor agonists improved motor and cognitive performance in PD, suggesting potential symptomatic benefits. However, further studies are needed to evaluate their long-term effects and their role in disease modification, especially considering ethnic and disease severity variations.

Efficacy of repetitive transcranial magnetic stimulation combined with peripheral magnetic stimulation on movement symptom and exploration of the optimal population in Parkinson's disease: A randomized controlled trial.

This study explores the efficacy of repetitive transcranial magnetic stimulation (rTMS) and rTMS combined with repetitive peripheral magnetic stimulation (rPMS) (hereinafter referred to as rTMS + rPMS) on motor symptoms and quality of life in Parkinson's disease (PD), and explores whether there are differences between the two treatment methods; At the same time, analyze data from different subgroups to explore the influencing factors, in order to find the most suitable treatment group. Eighty patients with PD were randomly divided into rTMS and rTMS + rPMS groups and administered 10 Hz rTMS, and 10 Hz rTMS + 25 Hz rPMS, respectively, for 10 days. Before and after treatment, the PD Motor Function Rating Scale (UPDRS Part III, 10m Walk Timing Test, Stand Up Walk Test Evaluation Scale (TUG)) and PD Quality of Life Questionnaire (PDQ-39) were used to evaluate the motor symptoms and quality of life. After quantifying the treatment effect, a comparative analysis of the efficacy before and after treatment was conducted. Simultaneously, we divided the two treatment groups into different subgroups, compared the subgroups under the same treatment method, analyzed the relevant factors affecting the treatment method, and found the most suitable treatment group. (1) After rTMS or rTMS + rPMS, all scoring scales improved compared to those before treatment (P < .05). Compared to rTMS, rTMS + rPMS resulted in greater improvements in overall motor function (UPDRS III) and quality of life (PDQ-39) (P < .05). (2) Patients with rigidity-based type as the main type may be the most suitable for these two treatment methods (P < .05).(3) There was no significant difference in treatment efficiency between the two treatment methods for patients with PD at different disease stages, sexes, or treatment ages(P > .05). Both rTMS and rTMS + rPMS can improve movement symptoms and quality of life in patients with PD. rTMS + rPMS was more beneficial for improving the overall motor function. Patients with rigidity-based type as the main type may be the most suitable for these two treatment methods. The therapies work in all age groups, all gender and irrespective of the disease stage with varying levodopa equivalent daily doses as well.

White matter lesions contribute to motor and non-motor disorders in Parkinson's disease: a critical review.

Parkinson's disease (PD) is a prevalent neurodegenerative disease, characterized by movement disorders and non-motor symptoms like cognitive impairment and depression. Degeneration of dopaminergic neurons in the substantia nigra and Lewy bodies have long been considered as main neuropathological changes. However, recent magnetic resonance imaging (MRI) studies have shown that white matter lesions (WMLs) were present in PD patients. WMLs are characterized by loss or impairment of myelin sheath in central nerve fibers, which are closely correlated with motor and cognitive dysfunction in PD. WMLs alterations precede nigrostriatal neuronal losses and can independently affect the clinical severity or characteristics of motor coordination in PD patients. Currently, the exact mechanism of WMLs involvement in the occurrence and development of PD remains unclear. It is speculated that WMLs may participate in the pathogenesis of PD by disrupting important connections in brain or promoting axonal degeneration. In this review, we will discuss the pathological changes and mechanisms of WMLs, elaborate the impact of WMLs on the progression of PD, clarify the importance of WMLs in PD pathogenesis, and thus provide novel targets for PD treatments.

Assessing Changes in Motor Function and Mobility in Individuals with Parkinson's Disease After 12 Sessions of Patient-Specific Adaptive Dynamic Cycling.

This pilot randomized controlled trial evaluated the effects of 12 sessions of patient-specific adaptive dynamic cycling (PSADC) versus non-adaptive cycling (NA) on motor function and mobility in individuals with Parkinson's disease (PD), using inertial measurement unit (IMU) sensors for objective assessment. Twenty-three participants with PD (13 in the PSADC group and 10 in the NA group) completed the study over a 4-week period. Motor function was measured using the Kinesia™ sensors and the MDS-UPDRS Motor III, while mobility was assessed with the TUG test using OPAL IMU sensors. The PSADC group showed significant improvements in MDS-UPDRS Motor III scores (t = 5.165, p < 0.001) and dopamine-sensitive symptoms (t = 4.629, p = 0.001), whereas the NA group did not improve. Both groups showed non-significant improvements in TUG time. IMU sensors provided continuous, quantitative, and unbiased measurements of motor function and mobility, offering a more precise and objective tracking of improvements over time. PSADC demonstrated enhanced treatment effects on PD motor function compared to NA while also reducing variability in individual responses. The integration of IMU sensors was essential for precise monitoring, supporting the potential of a data-driven, individualized exercise approach to optimize treatment outcomes for individuals with PD.

Occipital hypoperfusion and motor reserve in Parkinson's disease: an early-phase 18F-FP-CIT PET study.

Individual variability exists in parkinsonian motor symptoms despite a similar degree of nigrostriatal dopamine depletion in Parkinson's disease (PD), called motor reserve. We enrolled 397 patients newly diagnosed with PD who underwent dual-phase 18F-FP-CIT PET upon initial assessment. Individual motor reserve was estimated based on initial parkinsonian motor symptoms and striatal dopamine transporter availability using a residual model. Patients with low motor reserve (the lowest quartile group, n = 100) exhibited decreased uptake in the occipital region compared to those with high motor reserve (the highest quartile group, n = 100) on early-phase 18F-FP-CIT PET images. Patients with high motor reserve had a lower risk of conversion to dementia than the those with low motor reserve, whereas the effect of PD groups on the risk of dementia conversion was not mediated by occipital hypoperfusion. These findings suggest that cerebral hypoperfusion in the occipital region is associated with low motor reserve in patients with PD.

Motor learning is modulated by dopamine availability in the sensorimotor putamen.

Successful motor skill acquisition requires the dynamic interaction of multiple brain regions, with the striatum playing a critical role in this network. Animal studies suggest that dopaminergic mechanisms are involved in the regulation of motor learning-associated striatal plasticity. In humans, however, the contribution of nigrostriatal dopaminergic transmission to motor learning remains elusive beyond its well-characterized role in initiation and fluent execution of movements. In this prospective observational study, we investigated motor sequence learning in individuals who had undergone 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography for the differential diagnosis of Parkinson's disease (n = 41) and age-matched healthy controls (n = 20). We found that striatal dopamine transporter depletion exhibited distinct spatial patterns that were associated with impairments in motor sequence learning and the manifestation of Parkinsonian motor symptoms, respectively. Specifically, significant associations between striatal dopamine transporter depletion and impairments in motor sequence learning were confined to posterior putaminal regions, whereas significant associations of striatal dopamine transporter depletion with Parkinsonian motor symptom severity showed a widespread spatial pattern across the entire striatal volume with an anterior maximum. Normative functional connectivity analysis revealed that both behavioural domains shared largely overlapping connectivity patterns with the basal ganglia and supplementary motor area. However, apart from connectivity with more posterior parts of the supplementary motor area, significant functional connectivity with primary motor cortical areas was only present for striatal dopamine transporter availability-related modulation of online motor learning. Our findings indicate that striatal dopaminergic signalling plays a specific role in motor sequence learning beyond its influence on mere motor execution, implicating learning-related sensorimotor striatum recruitment and cortico-striatal plasticity as dopamine-dependent mechanisms.

Impact of Harmonization on MRI Radiomics Feature Variability Across Preprocessing Methods for Parkinson's Disease Motor Subtype Classification.

This study aimed to assess the reproducibility of MRI-derived radiomic features across multiple preprocessing methods for classifying Parkinson's disease (PD) motor subtypes and to evaluate the impact of ComBat harmonization on feature stability and machine learning performance. T1-weighted MRI scans from 140 PD patients (70 tremor-dominant and 70 postural instability gait difficulty) and 70 healthy controls were obtained from the Parkinson's Progression Markers Initiative (PPMI) database, acquired using different scanner models. Radiomic features were extracted from 16 brain regions using various preprocessing pipelines. ComBat harmonization was applied using a combined batch variable incorporating both scanner models and preprocessing methods. Intraclass correlation coefficients (ICC) and Kruskal-Wallis tests assessed feature reproducibility before and after harmonization. Feature selection was performed using Linear Support Vector Classifier with L1 regularization. Support vector machine classifiers were used for PD subtype classification. ComBat harmonization significantly improved feature reproducibility across all feature groups. The percentage of features showing excellent robustness (ICC ≥ 0.90) increased from 40.2 to 56.3% after harmonization. First-order statistic features showed the highest robustness, with 71.11% demonstrating excellent ICC after harmonization. The proportion of features significantly affected by preprocessing methods was reduced following harmonization. Classification accuracy improved dramatically, from a range of 34-75% before harmonization to 89-96% after harmonization across all preprocessing methods. AUC values similarly increased from 0.28-0.87 to 0.95-0.99 after harmonization. ComBat harmonization significantly enhanced the reproducibility of radiomic features across preprocessing methods and improved PD motor subtype classification performance. This study highlights the importance of harmonization in radiomics research for PD and suggests potential clinical applications in personalized treatment planning.

Electrode Location and Domain-Specific Cognitive Change Following Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) motor symptoms. DBS is also associated with postoperative cognitive change in some patients. Previous studies found associations between medial active electrode contacts and overall cognitive decline. Our current aim is to determine the relationship between active electrode contact location and domain-specific cognitive changes. A single-institution retrospective cohort study was conducted in patients with PD who underwent subthalamic nucleus (STN) DBS from August 05, 2010, to February 22, 2021, and received preoperative and postoperative neuropsychological testing. Standardized norm-referenced test z-scores were categorized into attention, executive function, language, verbal memory, and visuospatial domains. SD change scores were averaged to create domain-specific change scores. We identified anterior commissure/posterior commissure coordinates of active electrode contacts in atlas space. We evaluated differences in active electrode contact location between patients with a domain score decrease of at least 1 SD and less than 1 SD. We performed multiple variable linear regression controlling for age, sex, education, time from surgery to postoperative neuropsychological testing (follow-up duration), disease duration, preoperative unified Parkinson's disease rating scale off medication scores, and preoperative memory scores to determine the relationship between active electrode contact location and domain change. A total of 83 patients (male: n = 60, 72.3%) were included with a mean age of 63.6 ± 8.3 years, median disease duration of 9.0 [6.0, 11.5] years, and median follow-up duration of 8.0 [7.0, 11.0] months. More superior active electrode contact location in the left STN (P = .002) and higher preoperative memory scores (P < .0001) were associated with worsening memory. Active electrode contact location was not associated with change in other domains. In patients with PD who underwent STN DBS, we found an association between superior active electrode contacts in the left STN and verbal memory decline. Our study increases understanding of factors associated with cognitive change after DBS and may help inform postoperative programming.

Microbiome-based therapies for Parkinson's disease.

The human gut microbiome dysbiosis plays an important role in the pathogenesis of Parkinson's disease (PD). The bidirectional relationship between the enteric nervous system (ENS) and central nervous system (CNS) under the mediation of the gut-brain axis control the gastrointestinal functioning. This review article discusses key mechanisms by which modifications in the composition and function of the gut microbiota (GM) influence PD progression and motor control loss. Increased intestinal permeability, chronic inflammation, oxidative stress, α-synuclein aggregation, and neurotransmitter imbalances are some key factors that govern gastrointestinal pathology and PD progression. The bacterial taxa of the gut associated with PD development are discussed with emphasis on the enteric nervous system (ENS), as well as the impact of gut bacteria on dopamine production and levodopa metabolism. The pathophysiology and course of the disease are associated with several inflammatory markers, including TNF-α, IL-1β, and IL-6. Emerging therapeutic strategies targeting the gut microbiome include probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The article explored how dietary changes may affect the gut microbiota (GM) and the ways that can affect Parkinson's disease (PD), with a focus on nutrition-based, Mediterranean, and ketogenic diets. This comprehensive review synthesizes current evidence on the role of the gut microbiome in PD pathogenesis and explores its potential as a therapeutic target. Understanding these complex interactions may assist in the development of novel diagnostic tools and treatment options for this neurodegenerative disorder.

Atrophy-related corticospinal changes in advanced Parkinson's disease are associated with the genetic etiology of the disease

Background Compensatory mechanisms in Parkinson's disease (PD) are thought to explain the temporal delay between the beginning of the neurodegenerative process and the appearance of clinical signs. The enhanced structural integrity of the corticospinal tract was previously suggested as one of these mechanisms. Objective To understand the relations between corticospinal tract integrity and the anatomical, clinical, electrophysiological, and genetic PD characteristics. Methods We analyzed diffusion tensor imaging (DTI) fractional anisotropy (FA) data from 40 genotyped patients with PD (18 without known genetic cause, 11 with LRRK2-PD and 11 with GBA-PD) who were candidates for subthalamic deep brain stimulation (STN-DBS) and from 25 healthy, age-matched, controls. Results PD is associated with higher corticospinal FA values (p &lt; 0.001) that are negatively correlated with the disease duration (p = 0.032), confirming previous results. Higher FA values are negatively correlated with cerebral grey matter volumes (p &lt; 0.001) but not with the motor or cognitive PD characteristics, or with the subthalamic beta-oscillatory activity measured intra-operatively. Increased corticospinal FA values are strongly affected by the genetic etiology of PD, with higher values in the monogenic forms of the disease (p &lt; 0.001). The compensatory index, calculated by dividing the corticostriatal FA value by the cerebral grey matter volume, is highest in GBA-PD (p &lt; 0.001) at the time of evaluation for STN-DBS. Conclusions The genetic etiology of PD strongly shapes corticospinal tract changes along with disease-duration and cerebral grey matter atrophy. The changes may serve as compensatory mechanism.

High correlation of quantitative susceptibility mapping and echo intensity measurements of nigral iron overload in Parkinson's disease.

Quantitative susceptibility mapping (QSM) and transcranial sonography (TCS) offer proximal evaluations of iron load in the substantia nigra. Our prospective study aimed to investigate the relationship between QSM and TCS measurements of nigral iron content in patients with Parkinson's disease (PD). In secondary analyses, we wanted to explore the correlation of substantia nigra imaging data with clinical and laboratory findings. Eighteen magnetic resonance imaging and TCS examinations were performed in 15 PD patients at various disease stages. Susceptibility measures of substantia nigra were calculated from referenced QSM maps. Echogenicity of substantia nigra on TCS was measured planimetrically (echogenic area) and by digitized analysis (echo-intensity). Iron-related blood serum parameters were measured. Clinical assessments included the Unified PD Rating Scale and non-motor symptom scales. Substantia nigra susceptibility correlated with echogenic area (Pearson correlation, r = 0.53, p = 0.001) and echo-intensity (r = 0.78, p < 0.001). Individual asymmetry indices correlated between susceptibility and echogenic area measurements (r = 0.50, p = 0.042) and, more clearly, between susceptibility and echo-intensity measurements (r = 0.85, p < 0.001). Substantia nigra susceptibility (individual mean of bilateral measurements) correlated with serum transferrin saturation (Spearman test, r = 0.78, p < 0.001) and, by trend, with serum iron (r = 0.69, p = 0.004). Nigral echogenicity was not clearly related to serum values associated with iron metabolism. Susceptibility and echogenicity measurements were unrelated to PD duration, motor subtype, and severity of motor and non-motor symptoms. The present results support the assumption that iron accumulation is involved in the increase of nigral echogenicity in PD. Nigral echo-intensity probably reflects ferritin-bound iron, e.g. stored in microglia.

Intranasal AdipoRon Mitigated Anxiety and Depression-Like Behaviors in 6-OHDA-Induced Parkinson 's Disease Rat Model: Going Beyond Motor Symptoms.

Depression and anxiety are prevalent neuropsychiatric conditions among patients with Parkinson's disease (PD), which may manifest prior to motor symptoms. As levodopa, a prominent treatment for PD motor symptoms, provides few benefits for mood-related abnormalities, tackling non-motor symptoms is particularly important. AdipoRon (Ad), an adiponectin agonist, has demonstrated neuroprotective effects by suppressing neuroinflammatory responses and activating the AMPK/Sirt-1 signaling pathway. This study looked at the potential advantages and underlying mechanisms of intranasal Ad in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). We found that Ad at doses of 1 and 10µg for 21 days exhibited anxiolytic- and antidepressant effects in the open field (OF) test, elevated plus maze (EPM), sucrose splash test, and forced swimming test in a PD model caused by a unilateral 6-OHDA injection into the medial forebrain bundle (MFB). The Ad also lowered the levels of corticosterone in the blood, decreased inflammasome components (NLRP3, caspase 1, and IL-1β), and increased Sirt-1 protein levels in the prefrontal cortex (PFC) of PD rats. We conclude that Ad ameliorates anxious and depressive-like behaviors in the PD rat model through stimulating the AMPK/Sirt-1 signaling and blocking the NLRP3 inflammasome pathways in the PFC.

What Parkinson’s Disease Patients Say in Their Own Words about their Mood and Anxiety Symptoms

ObjectiveTo understand what Parkinson’s Disease (PD) patients report in their own words about their mood and anxiety problems using the Parkinson’s Disease Patient Report of Problems (PD-PROP). MethodsPatient-reported data from the PD-PROP (reporting most bothersome problems due to PD in their own words), Geriatric Depression Scale, MDS-UPDRS II, and the Euro-Q0L from the Fox Insight research database https://foxinsight.michaeljfox.org/ were examined using cross-sectional comparisons and logistic regression analyses to characterize non-depressive mood symptoms and anxiety. ResultsWe identified 21,487 participants who completed at least one PD-PROP questionnaire. Four categories of non-depressive mood symptoms (Anxiety/Worry, Loneliness/Isolation, Negative Emotions NOS (Not Otherwise Specified), Death/Suicidal Ideation) were identified. Women were much more likely than men to report non-depressive mood symptoms as a bothersome PD-related problem. The frequency of Anxiety/Worry reporting decreased with longer duration of PD while Loneliness/Isolation increased. More severe PD motor impairment, as measured by the MDS-UPDRS II, was associated with increased reporting of Negative Emotions and Loneliness/Isolation. Higher Euro-QoL, indicating better quality of life, was associated with decreased reporting of Loneliness/Isolation. Death/Suicidal Ideation was only reported by a small number of participants (<0.5%). ConclusionsWomen were more likely than men with PD to identify Anxiety/Worry, Negative Emotions, and Loneliness/Isolation as problems. This finding and the higher prevalence of bothersome loneliness/isolation as PD duration increases can guide monitoring for these issues.

The Effect of Dysautonomia on Motor, Behavioral, and Cognitive Fluctuations in Parkinson's Disease.

Motor and nonmotor fluctuations adversely impact the quality of life in Parkinson's disease (PD). Dysautonomia, a feature frequently associated with PD and a possible adverse effect of dopaminergic therapy, may be comorbid with fluctuations. We sought to evaluate the effect of dysautonomia on motor and nonmotor fluctuations in PD. Two hundred subjects with PD were evaluated in both on and off dopamine states to assess changes in symptoms related to dopaminergic fluctuations. Multivariable logistic regression was performed to assess the association of dysautonomia with motor, cognitive, and psychiatric worsening from on to off states with adjustment for disease duration, levodopa equivalent daily dosage (LEDD), and dopamine-agonist LEDD. Subjects with dysautonomia had greater odds of clinically meaningful change in motor features (odds ratio [OR]: 3.0), cognition (OR: 3.4), and anxiety (OR: 4.3) compared to those without dysautonomia. Dysautonomia may be a contributory mechanism behind fluctuations in PD. The exact nature of this relationship deserves further evaluation. © 2024 International Parkinson and Movement Disorder Society.

Impairment of Neuronal Activity in the Dorsolateral Prefrontal Cortex Occurs Early in Parkinsonism.

Parkinson's disease (PD) is often characterized by altered rates and patterns of neuronal activity in the sensorimotor regions of the basal ganglia thalamocortical network. Little is known, however, regarding how neuronal activity in the executive control network of the brain changes in the parkinsonian condition. Investigate the impact of parkinsonism on neuronal activity in the dorsolateral prefrontal cortex (DLPFC), a key region in executive control, during a go/nogo reaching task. Using a within-subject design, single and multi-unit neuronal activity was recorded in the DLPFC of a nonhuman primate before and after the induction of mild parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coincident with development of mild parkinsonian motor signs, there was a marked reduction in the percentage of DLPFC cells with significant task-related firing rate modulation during go and nogo conditions. These results suggest that DLPFC dysfunction may occur early in parkinsonism and contribute to cognitive impairments and disrupted executive function often observed in PD patients.