Severity Of Motor Symptoms Research Articles

Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson's disease.

Mitochondrial dysfunction plays an important role in Parkinson's disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. We investigated the links between blood mtDNA-CN and PD severity and risk using the Accelerating Medicines Partnership program for Parkinson's Disease dataset, replicating our results in the UK Biobank. Our findings reveal that reduced blood mtDNA-CN levels are associated with heightened PD risk and increased severity of motor symptoms and olfactory dysfunction. We estimated blood cell composition using complete blood cell profile when available or RNA-sequencing data as a surrogate. After adjusting for blood cell composition, the associations between mtDNA-CN and PD risk and clinical symptoms became non-significant. Bidirectional Mendelian randomization analysis also found no evidence of a direct causal relationship between blood mtDNA-CN and PD susceptibility. Hence peripheral inflammatory immune responses rather than mitochondrial dysfunction underpin these previously identified associations in PD.

Motor learning is modulated by dopamine availability in the sensorimotor putamen

Abstract 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 (DaT) 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 DaT depletion and impairments in motor sequence learning were confined to posterior putaminal regions, whereas significant associations of striatal DaT 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 behavioral 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 DaT availability-related modulation of online motor learning. Our findings indicate that striatal dopaminergic signaling 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.

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.

Senolytic treatment diminishes microglia and decreases severity of experimental autoimmune encephalomyelitis

BackgroundThe role of senescence in disease contexts is complex, however there is considerable evidence that depletion of senescent cells improves outcomes in a variety of contexts particularly related to aging, cognition, and neurodegeneration. Much research has shown previously that inflammation can promote cellular senescence. Microglia are a central nervous system innate immune cell that undergo senescence with aging and during neurodegeneration. The contribution of senescent microglia to multiple sclerosis, an inflammatory neurodegenerative disease, is not clear, but microglia are strongly implicated in chronic active lesion pathology, tissue injury, and disease progression. Drugs that could specifically eliminate dysregulated microglia in multiple sclerosis are therefore of great interest to the field.ResultsA single-cell analysis of brain tissue from mice subjected to experimental autoimmune encephalomyelitis (EAE), a mouse model of CNS inflammation that models aspects of multiple sclerosis (MS), identified microglia with a strong transcriptional signature of senescence including the presence of BCL2-family gene transcripts. Microglia expressing Bcl2l1 had higher expression of pro-inflammatory and senescence associated genes than their Bcl2l1 negative counterparts in EAE, suggesting they may exacerbate inflammation. Notably, in human single-nucleus sequencing from MS, BCL2L1 positive microglia were enriched in lesions with active inflammatory pathology, and likewise demonstrated increased expression of immune genes suggesting they may be proinflammatory and contribute to disease processes in chronic active lesions. Employing a small molecule BCL2-family inhibitor, Navitoclax (ABT-263), significantly reduced the presence of microglia and macrophages in the EAE spinal cord, suggesting that these cells can be targeted by senolytic treatment. ABT-263 treatment had a profound effect on EAE mice: decreasing motor symptom severity, improving visual acuity, promoting neuronal survival, and decreasing white matter inflammation.ConclusionThese results support the hypothesis that microglia and macrophages exhibit transcriptional features of cellular senescence in EAE and MS, and that microglia expressing Bcl2l1 demonstrate a proinflammatory signature that may exacerbate inflammation resulting in negative outcomes in neuroinflammatory disease. Depleting microglia and macrophages using a senolytic results in robust improvement in EAE disease severity, including across measures of neurodegeneration, inflammation, and demyelination, and may therefore represent a novel strategy to address disease progression in multiple sclerosis.

Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder that can be associated with antibodies against surface antigens (glycine receptor (GlyR), dipeptidyl-peptidase-like-protein-6) and intracellular antigens (glutamate decarboxylase (GAD65), amphiphysin). We report clinico-pathologic findings of a PERM patient with coexisting GlyR and GAD65 antibodies. A 75-year-old man presented with myoclonus and pain of the legs, subsequently developed severe motor symptoms, hyperekplexia, a pronounced startle reflex, hallucinations, dysautonomia, and died 10 months after onset despite extensive immunotherapy, symptomatic treatment, and continuous intensive care support. Immunotherapy comprised corticosteroids, IVIG, plasmapheresis, immunoadsorption, cyclophosphamide, and bortezomib. Intensive care treatment and permanent isoflurane sedation was required for more than 20 weeks. CNS tissue revealed neuronal loss, astrogliosis and microgliosis, representing a pallido-nigro-dentato-bulbar-spinal degeneration pattern, specifically along GlyR and GAD expression sites. Neurons showed pSTAT1, MHC class I, and GRP78 upregulation. Inflammation was moderate and characterized by CD8+ T cells and single CD20+/CD79a+ B/plasma cells. Focal tau-positive thread-like deposits were detected in gliotic brainstem areas. In the spinal cord, GlyR, glycine transporter-2, and GAD67 expression were strongly reduced. A possible potentiating effect of pathogenic GlyR antibodies together with T cells directed against neurons may have led to the severe and progressive clinical course.

Modulation of Cerebellar Oscillations with Subthalamic Stimulation in Patients with Parkinson's Disease.

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has emerged as a potent treatment for alleviating motor symptoms in Parkinson's disease (PD). Despite its effectiveness, the impact of high frequency STN-DBS on cerebellar oscillations remains unclear, posing an intriguing challenge for neural modulation. Given the direct and indirect connections between the STN and cerebellum, we investigated whether STN-DBS affects cerebellar oscillations. To observe the effects of STN-DBS on cerebellar oscillations in patients with PD. We recruited 15 PD patients receiving STN-DBS. Electroencephalographic (EEG) signals were recorded from cerebellar regions during resting-state conditions in both the OFF-DBS and STN-DBS conditions. Our analyses centered on spectral features, particularly theta and beta oscillations, guided by prior research and correlation tests to investigate the relationship between oscillatory changes and motor symptom severity. In the mid-cerebellar (Cbz) region, we observed a significant increase in the relative power in all frequency bands, including theta and beta oscillations during STN-DBS, showing the global effect of DBS. Importantly, the correlation results indicated significant associations between mid-cerebellar (Cbz) beta power during the OFF condition and motor severity, which were not evident during STN-DBS. Interestingly, correlations between beta power and motor severity were not observed at the mid-occipital (Oz) and mid-frontal (Cz) regions. Notably, signal similarity analyses demonstrated no evidence of volume conduction effects between the mid-cerebellar (Cbz) and nearby mid-occipital (Oz) regions. While these findings provide valuable insights into the complex interplay between STN-DBS and neural oscillations, further research is essential to decipher their precise functional significance and clinical implications. Understanding these intricacies may contribute to the optimization of DBS therapies for PD.

Implication of nutrition in severity of symptoms and treatments in quality of life in Parkinson's disease: a systematic review.

Therefore, this review aims to evaluate whether nutritional alterations are related either to the severity of motor and non-motor symptoms through the gut-brain axis or to the different treatments for PD and whether all of this, in turn, impacts the QoL of patients. A systematic review was carried out in MEDLINE and EMBASE databases, and Mendeley from 2000 to June 2024, searching for articles related to nutritional alterations in PD that alter patients' QoL. A total of 14 articles (2,187 participants) of 924 records were included. Among the 14 studies examined, two investigated the relationship between nutritional status and QoL in patients with PD. Poor nutritional status was associated with lower QoL scores. Four studies explored the connection between nutritional status and its impact on both motor and non-motor symptoms (psychiatric disturbances, cognitive impairment, and fatigue), revealing a link between nutritional status, activities of daily living, and the severity of motor symptoms. Three studies identified changes in body weight associated with the severity of symptoms related to mobility issues in PD patients. Three studies investigated the relationship between different PD treatments and their interaction with changes in weight and energy metabolism, highlighting that weight loss in the early stages of PD needs adequate monitoring of different treatments, as well as the interaction between the central and peripheral nervous systems in regulating these processes. Finally, two studies investigated how gastrointestinal alterations and changes in the microbiota were related to cognitive status, thus identifying them as risk factors and early signs of PD. The systematic review highlighted the significant relationship between nutritional status and QoL in patients with PD, as well as how the PD treatments influenced their weight. An association was also observed in the gut-brain axis, where adequate nutritional status influenced the balance of intestinal microbiota, slowing cognitive decline, improving activities of daily living, and the QoL of PD patients. It is confirmed that the nutritional status of patients influenced both motor and non-motor symptoms of the disease, and therefore their QoL.

Variability in Vowel Space in Parkinson's Disease: Associations With Cognitive and Motor Impairment.

People with Parkinson's disease (PwP) typically experience impairments in vowel articulation; however, less is known about how this measure varies with speech task type and clinical characteristics such as cognitive impairment. We characterized vowel space in PwP with and without mild cognitive impairment (MCI) comparing performance across phonation, reading, and picture description tasks. We evaluated associations between vowel space and cognitive impairment, as well as motor symptom severity to elucidate the factors contributing to variability in this acoustic measure. PwP (n = 48) and age-matched controls (n = 15) performed sustained phonation of corner vowels, a reading passage, and a picture description task (Cookie Theft picture). PwP participants were classified as with normal cognition (PD-NC) or MCI (PD-MCI), and motor symptoms were assessed using the Movement Disorders Society Unified Parkingson's Disease Rating Scale Part III (MDS-UPDRS Part III). Vowel articulation index (VAI) for each task and mean difference in VAI between tasks was compared between the groups using linear mixed models adjusted for age, sex, and education. The impact of motor severity was assessed by additionally adjusting the model for MDS-UPDRS Part III score. In the adjusted mixed model, mean VAI was significantly lower in the PD-MCI group compared to the PD-NC group for all tasks. Within participants, adjusted mean differences demonstrated that all groups declined in VAI when sustained phonation was compared to either reading or picture description tasks. Adjustment for MDS-UPDRS Part III did not alter the results, suggesting no major association of motor impairment with vowel space variability within or between individuals or groups. Variability in vowel space is impacted by cognitive impairment and speech task in PwP. These findings are relevant to the further development of speech markers in PwP and other neurogenerative diseases that impact both cognitive and motor functions.

Atrophy of cerebellar lobule VI and primary motor cortex in cervical dystonia - a region of interest-based study.

Recently, a network model of cervical dystonia (CD) has been adopted that implicates nodes and pathways involving cerebellar, basal-ganglia and cortico-cortical connections. Although functional changes in the cerebello-thalamo-cortical network in dystonia have been reported in several studies, structural information of this network remain sparse. To characterize the structural properties of the cerebellar motor network in isolated CD patients. This includes cerebellar lobules involved in motor processing, the dentate nucleus (DN), the thalamus, and the primary motor cortex (M1). Magnetic resonance imaging data of 18 CD patients and 18 healthy control subjects were acquired. In CD patients, the motor part of the Toronto Western Spasmodic Torticollis Rating Scale was assessed to evaluate motor symptom severity. The volume of cerebellar lobules I-VI and VIII, the DN and thalamus, and the cortical thickness (CT) of M1 were determined for a region of interest (ROI)-based quantitative analysis. Volumes/CT of these ROIs were compared between groups and associated with motor symptom severity in patients. The volume of lobule VI and the CT of M1 were reduced in CD patients. The volumes of the other ROIs were not different between groups. No association was identified between the structural properties of lobule VI or M1 and the severity of CD motor symptoms. Atrophy within the cerebellum and M1 contributes to CD's complex motor network pathology. Further investigations are needed to ascertain the mechanisms underlying the local volume loss.

Patient Experience and Feasibility of a Remote Monitoring System in Parkinson's Disease.

Remote monitoring systems have the potential to measure symptoms and treatment effects in people with Parkinson's disease (PwP) in the home environment. However, information about user experience and long-term compliance of such systems in a large group of PwP with relatively severe PD symptoms is lacking. The aim was to gain insight into user experience and long-term compliance of a smartwatch (to be worn 24/7) and an online dashboard to report falls and receive feedback of data. We analyzed the data of the "Bringing Parkinson Care Back Home" study, a 1-year observational cohort study in 200 PwP with a fall history. User experience, compliance, and reasons for noncompliance were described. Multiple Cox regression models were used to identify determinants of 1-year compliance. We included 200 PwP (mean age: 69 years, 37% women), of whom 116 (58%) completed the 1-year study. The main reasons for dropping out of the study were technical problems (61 of 118 reasons). Median wear time of the smartwatch was 17.5 h/day. The online dashboard was used by 77% of participants to report falls. Smartphone possession, shorter disease duration, more severe motor symptoms, and less-severe freezing and balance problems, but not age and gender, were associated with a higher likelihood of 1-year compliance. The 1-year compliance with this specific smartwatch was moderate, and the user experience was generally good, except battery life and data transfer. Future studies can build on these findings by incorporating a smartwatch that is less prone to technical issues.

NEUROINFLAMMATION IN PARKINSON’S DISEASE: A STUDY WITH [11C]PBR28 PET AND CEREBROSPINAL FLUID MARKERS

ObjectiveTo investigate neuroinflammation in Parkinson’s disease (PD) with [11C]PBR28 positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers, and the relationship to dopaminergic functioning measured with 6-[18F]-fluoro-L-dopa ([18F]FDOPA) PET. MethodsThe clinical cohort consisted of 20 subjects with PD and 51 healthy controls (HC). All HC and 15 PD participants underwent [11C]PBR28 High Resolution Research Tomograph (HRRT) PET for the quantitative assessment of cerebral binding to the translocator protein (TSPO), a neuroinflammation marker. CSF samples were available from 17 subjects with PD and 21 HC and were examined for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), neurogranin (NG), alpha-synuclein (aSyn) and oligo-alpha-synuclein. All subjects with PD underwent [18F]FDOPA HRRT PET. ResultsWhile the subjects with PD and HC did not differ in the total volume of distribution (VT) of [11C]PBR28 in any studied brain regions, higher levels of neuroinflammation and neurodegeneration CSF biomarkers sTREM2 and NG, respectively were associated with more severe motor symptoms evaluated by The Unified Parkinson’s Disease Rating Scale motor part (UPDRS-III) (r = 0.52, p=0.041 and r = 0.59, p=0.016 respectively). Additionally, in the PD group increased [11C]PBR28 VT in the basal ganglia and substantia nigra (SN) was related to higher levels of neuroinflammation biomarker YKL-40 (p <0.01). ConclusionAssociations between CSF biomarkers, motor disability and [11C]PBR28 VT in the striatum and SN may support a role for neuroinflammation in PD.

Retrospective analysis of diet and gut microbiota diversity and clinical pharmacology outcomes in patients with Parkinsonism syndrome

BackgroundParkinson's disease (PD) is a global neurodegenerative ailment impacting millions, causes significant degeneration of dopaminergic neurons in the substantia nigra. Emerging research underscores the gut microbiota's role in PD onset. Yet, investigations in Chinese demographics are lacking. This study thus targets a retrospective examination of gut microbiota variety and clinical aspects in Chinese PD patients. MethodsWe retrospectively analyzed 50 PD patients' clinical data (admitted May 2021–April 2022) and compared their gut microbiota composition and abundance via 16S rDNA V3-V4 region sequencing against 50 healthy controls. The study also explored links between disease severity and PD patients' gut microbiota. ResultsWe found that the gut microbiota diversity was increased in PD patients. Specifically, phyla Firmicutes, Actinobacteria, and Proteobacteria were more abundant, whereas Bacteroidetes was less abundant compared to controls. Gut microbiota diversity did not vary between early-vs. late-onset PD, tremor-dominant vs. non-tremor-dominant, or constipation-associated vs. non-constipation-associated subtypes. The abundance of Firmicutes was positively correlated with UPDRS (Unified Parkinson's Disease Rating Scale) III score, NMSS (Non-Motor Symptoms Scale) score, Wexner score, and PDQ-39 (Parkinson's Disease Questionnaire-39) score; the abundance of Actinobacteria was positively correlated with UPDRS III, NMSS, Wexner, and PDQ-39 scores; and the abundance of Bacteroidetes was negatively correlated with UPDRS III, NMSS, Wexner, and PDQ-39 scores. At the family level, the abundance of Bifidobacteriaceae, Enterobacteriaceae, and Porphyromonadaceae was positively correlated with UPDRS III, NMSS, and PDQ-39 scores. ConclusionCompared with healthy individuals, PD patients have increased gut microbiota diversity, and the abundance of Bifidobacteriaceae, Enterobacteriaceae, and Porphyromonadaceae is associated with the severity of both motor and non-motor symptoms in PD patients.

Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia.

Myoclonus dystonia due to a pathogenic variant in SGCE (MYC/DYT-SGCE) is a rare condition involving a motor phenotype associating myoclonus and dystonia. Dysfunction within the networks relying on the cortex, cerebellum, and basal ganglia was presumed to underpin the clinical manifestations. However, the microarchitectural abnormalities within these structures and related pathways are unknown. Here, we investigated the microarchitectural brain abnormalities related to the motor phenotype in MYC/DYT-SGCE. We used neurite orientation dispersion and density imaging, a multicompartment tissue model of diffusion neuroimaging, to compare microarchitectural neurite organization in MYC/DYT-SGCE patients and healthy volunteers (HVs). Neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) were derived and correlated with the severity of motor symptoms. Fractional anisotropy (FA) and mean diffusivity (MD) derived from the diffusion tensor approach were also analyzed. In addition, we studied the pathways that correlated with motor symptom severity using tractography analysis. Eighteen MYC/DYT-SGCE patients and 24 HVs were analyzed. MYC/DYT-SGCE patients showed an increase of ODI and a decrease of FA within their motor cerebellum. More severe dystonia was associated with lower ODI and NDI and higher FA within motor cerebellar cortex, as well as with lower NDI and higher ISOVF and MD within the corticopontocerebellar and spinocerebellar pathways. No association was found between myoclonus severity and diffusion parameters. In MYC/DYT-SGCE, we found microstructural reorganization of the motor cerebellum. Structural change in the cerebellar afferent pathways that relay inputs from the spinal cord and the cerebral cortex were specifically associated with the severity of dystonia.

Clinical symptoms and neuroanatomical substrates of daytime sleepiness in Parkinson’s disease

Clinical and neuroanatomical correlates of daytime sleepiness in Parkinson’s disease (PD) remain inconsistent in the literature. Two studies were conducted here. The first evaluated the interrelation between non-motor and motor symptoms, using a principal component analysis, associated with daytime sleepiness in PD. The second identified the neuroanatomical substrates associated with daytime sleepiness in PD using magnetic resonance imaging (MRI). In the first study, 77 participants with PD completed an extensive clinical, cognitive testing and a polysomnographic recording. In the second study, 29 PD participants also underwent MRI acquisition of T1-weighted images. Vertex-based cortical and subcortical surface analysis, deformation-based morphometry, and voxel-based morphometry were performed to assess the association between daytime sleepiness severity and structural brain changes in participants. In both studies, the severity of daytime sleepiness and the presence of excessive daytime sleepiness (EDS; total score >10) were measured using the Epworth Sleepiness Scale. We found that individuals with EDS had a higher score on a component including higher dosage of dopamine receptor agonists, motor symptoms severity, shorter sleep latency, and greater sleep efficiency. Moreover, increased daytime sleepiness severity was associated with a larger surface area in the right insula, contracted surfaces in the right putamen and right lateral amygdala, and a larger surface in the right posterior amygdala. Hence, daytime sleepiness in PD was associated with dopaminergic receptor agonists dosage, motor impairment, and objective sleep measures. Moreover, neuroanatomical changes in cortical and subcortical regions related to vigilance, motor, and emotional states were associated with more severe daytime sleepiness.

Cognitive Performance Between Latino and White Non-Latino Individuals With Parkinson's Disease.

Cognitive impairment is a common nonmotor symptom in Parkinson's disease (PD). Individuals of Latino background are traditionally underrepresented in research on PD. Despite the fact that Latinos comprise 18% of the U.S. population, they commonly make up less than 5% of samples in studies of PD. Emerging evidence suggests that Latino individuals with PD may experience disparities relative to White non-Latinos in terms of having more severe motor symptoms, more severe depressive symptoms, and worse health-related quality of life. The purpose of the present study was to investigate differences in cognitive performance between Latino and White non-Latino individuals with PD and examine correlates of cognitive performance. Data were obtained from the Parkinson's Progression Markers Initiative. Participants included 60 Latino individuals with PD and 1,009 White non-Latino individuals with PD, all of whom were followed annually for up to 5 years. Participants completed neuropsychological tests of attention and working memory, processing speed, visuospatial functioning, verbal fluency, and immediate and delayed memory and recall. Relative to White non-Latino individuals with PD, Latino individuals with PD had significantly lower scores on the global measure of cognitive functioning, a test of processing speed, and tests of working memory and attention. Years of education was the strongest correlate of performance in these three cognitive domains among individuals in the Latino group. These findings provide initial evidence of disparities in cognitive functioning among Latino individuals with PD. Educational disadvantages may be one potential driver of these disparities.

Motor progression trajectories and risk of mild cognitive impairment in Parkinson's disease: A latent class trajectory model from PPMI cohort.

Rare studies have investigated the association between heterogeneity of motor progression and risk of early cognitive impairment in Parkinson's disease (PD). In this study, we aim to identify distinct trajectories of motor progression longitudinally and investigate their impact on predicting mild cognitive impairment (MCI). A 5-year cohort including 415 PD patients at baseline was collected from the Parkinson's Progression Markers Initiative. The severity of motor symptoms was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III. The latent class trajectory model and nonlinear mixed-effects model were used to analyze and delineate the longitudinal changes in motor symptoms. Propensity score matching (PSM) was used to minimize the impact of potential confounders. Cox proportional hazard models were applied to calculate hazard ratios for MCI, and a Kaplan-Meier curve was generated using the occurrence of MCI during the follow-up as the time-to-event. Two latent trajectories were identified: a mild and remitting motor symptoms class (Class 1, 33.01%) and a severe and progressive motor symptom class (Class 2, 66.99%). Patients in Class 2 initially exhibited severe motor symptoms that worsened progressively despite receiving anti-PD medications. In comparison, patients in Class 1 exhibited milder symptoms that improved following drug therapy and a slower progression. During a 5-year follow-up, patients in Class 2 showed a higher risk of developing MCI compared to those in Class 1 before PSM (Log-Rank 28.58, p < 0.001) and after PSM (Log-Rank 8.20, p = 0.004). PD patients with severe and progressive motor symptoms are more likely to develop MCI than those with mild and stable motor symptoms.

Longitudinal evaluation of polyneuropathy in Parkinson’s disease

BackgroundIncreasing evidence indicates a higher prevalence of polyneuropathy (PNP) in Parkinson’s disease (PD). However, the involvement of large fiber neuropathy in PD still remains poorly understood. Given the lack of longitudinal data, we investigated the course of PNP associated with PD.MethodsIn total, 41 PD patients underwent comprehensive clinical evaluation including motor and non-motor assessments as well as nerve conduction studies at baseline and at 2 years of follow-up. The definition of PNP was based on electrophysiological standard criteria. Common causes of PNP were excluded.ResultsAt baseline, PNP was diagnosed in 65.85% of PD patients via electroneurography. Patients with PNP presented with higher age (p = 0.019) and PD motor symptom severity (UPDRS III; p < 0.001). Over the course of 2 years, PNP deteriorated in 21.95% of cases, and 26.83% remained without PNP. Deterioration of nerve amplitude was most prevalent in the median sensory nerve affecting 57.58% of all PD cases with an overall reduction of median sensory nerve amplitude of 45.0%. With regard to PD phenotype, PNP progression was observed in 33.33% of the tremor dominant and 23.81% of the postural instability/gait difficulties subtype. Decrease of sural nerve amplitude correlated with lower quality of life (PDQ-39, p = 0.037) and worse cognitive status at baseline (MoCA, p = 0.042).ConclusionThe study confirms the high PNP rate in PD, and demonstrates a significant electrophysiological progression also involving nerves of the upper extremities. Longitudinal studies with larger cohorts are urgently needed and should elucidate the link between PD and PNP with the underlying pathomechanisms.

A Characterization of Central Auditory Processing in Parkinson's Disease.

Research indicates that people with Parkinson's disease (PwPs) may experience challenges in both peripheral and central auditory processing, although findings are inconsistent across studies. Due to the diversity of auditory measures used, there is a need for standardized, replicable hearing assessments to clarify which aspects of audition are impacted in PWPs and whether they are linked to motor and non-motor symptoms. To characterize auditory processes and their possible alteration in PwPs. To address this, we collected a comprehensive set of standardized measures of audition using PART, a digital testing platform designed to facilitate replication. Additionally, we examined the relationship between auditory, cognitive, and clinical variables in PwPs. We included 44 PwPs and 54 age and education matched healthy controls. Assessments included detection of diotic and dichotic frequency modulation, temporal gaps, spectro-temporal broad-band modulation, and speech-on-speech masking. We found no statistically significant differences in auditory processing measures between PwPs and the comparison group (ps > 0.07). In PwPs, an auditory processing composite score showed significant medium size correlations with cognitive measures (0.39 < r<0.41, ps < 0.02) and clinical variables of motor symptom severity, quality of life, depression, and caretaker burden (0.33 < r<0.52, ps < 0.03). While larger datasets are needed to clarify whether PwPs experience more auditory difficulties than healthy controls, our results underscore the importance of considering auditory processing on the symptomatic spectrum of Parkinson's disease using standardized replicable methodologies.

Diffusion indices alteration in major white matter tracts of children with tic disorder using TRACULA

BackgroundTic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis.MethodsWe analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts.ResultsOur findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation.ConclusionThese results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis.

The correlation between rapid eye movement sleep behavior disorder and the progress of Parkinson's disease: a systematic review and meta-analysis.

This meta-analysis was conducted to evaluate potential differences in symptoms between PD patients with or without RBD. A systematic search was conducted in PubMed, Cochrane, Embase, and Web of Science databases (as of August 16, 2023), to identify relevant studies on PD and RBD. Statistical analysis was performed using Stata 15.0. Continuous variables were analyzed using the standardized mean difference (SMD) and 95% confidence interval (95% CI), while count data were assessed using the odds ratio (OR) and 95% CI as statistical effect sizes. Heterogeneity among all included studies was tested; for studies with low heterogeneity (I2 < 50%), a fixed-effects model was used to calculate statistical results. For studies with relatively high heterogeneity (I2 > 50%), a random-effects model was applied, followed by sensitivity and subgroup analyses to identify sources of heterogeneity. A total of 5,672 subjects were involved in this study. Compared to the NRBD group, the UPDRS-III score in the RBD group was significantly higher (SMD = 0.20, 95% CI: [0.11, 0.29], P < 0.001), and the Hoehn-Yahr score in the RBD group was also significantly higher (SMD = 0.29, 95% CI: [0.03, 0.55], P < 0.001). Patients with PD in the RBD group had more severe cognitive impairments than those in the NRBD group (SMD = -0.30, 95% CI: [-0.48, -0.11], P < 0.001). The incidence of hallucination in PD patients in the RBD group was 3.0 times that of the NRBD group (OR = 3.0, 95% CI: [2.15, 4.20], P = 0.110). PD patients in the RBD group also experienced more severe anxiety symptoms (SMD = 0.13, 95% CI: [-0.26, 0.51], P < 0.001), had higher scores in depression scales (SMD = 0.22, 95% CI: [0.02, 0.43], P < 0.001), and higher scores in sleep disorder scales than those in NRBD group (SMD = 0.10, 95% CI: [-0.11, 0.31], P < 0.001). Results show PD patients with co-occurring RBD have more severe motor and non-motor symptoms likely due to overlapping affected regions in RBD and PD-related pathology, plus broader neurodegeneration seen in PD patients with RBD. https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42023476331.