Early-stage Parkinson's Disease Research Articles

Cortical and Subcortical Changes in MEG Activity Reflect Parkinson’s Progression over a Period of 7 Years

In this study of early functional changes in Parkinson’s disease (PD), we aimed to provide a comprehensive assessment of the development of changes in both cortical and subcortical neurophysiological brain activity, including their association with clinical measures of disease severity. Repeated resting-state MEG recordings and clinical assessments were obtained in the context of a unique longitudinal cohort study over a seven-year period using a multiple longitudinal design. We used linear mixed-models to analyze the relationship between neurophysiological (spectral power and functional connectivity) and clinical data. At baseline, early-stage (drug-naïve) PD patients demonstrated spectral slowing compared to healthy controls in both subcortical and cortical brain regions, most outspoken in the latter. Over time, spectral slowing progressed in strong association with clinical measures of disease progression (cognitive and motor). Global functional connectivity was not different between groups at baseline and hardly changed over time. Therefore, investigation of associations with clinical measures of disease progression were not deemed useful. An analysis of individual connections demonstrated differences between groups at baseline (higher frontal theta, lower parieto-occipital alpha2 band functional connectivity) and over time in PD patients (increase in frontal delta and theta band functional connectivity). Our results suggest that spectral measures are promising candidates in the search for non-invasive markers of both early-stage PD and of the ongoing disease process.

Retraction of "Activated Microglia in the Early Stage of a Rat Model of Parkinson's Disease: Revealed by PET-MRI Imaging by [18F]DPA-714 Targeting TSPO".

In the past decades, translocator protein (TSPO) has been considered as an in vivo biomarker to measure the presence of neuroinflammatory reactions. In this study, expression of TSPO was quantified via [18F]DPA-714 positron emission tomography-magnetic resonance imaging (PET-MRI) imaging to investigate the effects of microglial activation associated with motor behavioral impairments in the 6-hydroxydopamine (6-OHDA)-treated rodent model of Parkinson's disease (PD). [18F]FDG PET-MRI (for non-specific inflammation), [18F]D6-FP-(+)-DTBZ PET-MRI (for damaged dopaminergic neurons), post-PET immunofluorescence, and Pearson's correlation analyses were also performed. The time course of the striatal [18F]DPA-714 binding ratio elevated in 6-OHDA-treated rats during 1-3 weeks post-treatment, with the peak TSPO binding in the 1st week. No differences between bilateral striatum in [18F]FDG PET imaging were found. Moreover, an obvious correlation between [18F]DPA-714 SUVRR/L and rotation numbers was found (r = 0.434, *p = 0.049). No correlation between [18F]FDG SUVRR/L and rotation behavior was found. [18F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.

Activated Microglia in the Early Stage of a Rat Model of Parkinson's Disease: Revealed by PET-MRI Imaging by [18F]DPA-714 Targeting TSPO.

In the past decades, translocator protein (TSPO) has been considered as an in vivo biomarker to measure the presence of neuroinflammatory reactions. In this study, expression of TSPO was quantified via [18F]DPA-714 positron emission tomography-magnetic resonance imaging (PET-MRI) to investigate the effects of microglial activation associated with motor behavioral impairments in the 6-hydroxydopamine (6-OHDA)-treated rodent model of Parkinson's disease (PD). [18F]FDG PET-MRI (for non-specific inflammation), [18F]D6-FP-(+)-DTBZ PET-MRI (for damaged dopaminergic (DA) neurons), post-PET immunofluorescence, and Pearson's correlation analyses were also performed. The time course of striatal [18F]DPA-714 binding ratio was elevated in 6-OHDA-treated rats during 1-3 weeks post-treatments, with peak TSPO binding in the 1st week. No difference between the bilateral striatum in [18F]FDG PET imaging were found. Moreover, an obvious correlation between [18F]DPA-714 SUVRR/L and rotation numbers was found (r = 0.434, *p = 0.049). No correlation between [18F]FDG SUVRR/L and rotation behavior was found. [18F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.

Autonomic control of heart and vessels in patients with very early stage of Parkinson disease

Objective. Non-motor symptoms including those reflecting autonomic cardiovascular dysregulation are often present in Parkinson disease. It is unclear whether it is possible to detect cardiovascular autonomic dysregulation in the very early stage of Parkinson disease potentially supporting the concept of the upstream propagation of nervous system damage through autonomic nerves. We hypothesized that cardiovascular dysregulation should precede the motor symptoms and at the time of their occurrence autonomic dysregulation should be clearly demonstrable. Therefore, the aim of this study was to assess the various aspects of autonomic cardiovascular control in the very early stage of Parkinson disease. Approach. We performed prospective case-control study on 19 patients with Parkinson disease (<6 months after motor signs occurrence) and 19 healthy control subjects. For each phase of study protocol (supine, head-up tilt, supine recovery), we calculated a wide array of cardiovascular control related parameters reflecting cardiac chronotropic, cardiac inotropic and vasomotor control and baroreflex mediated cardiovascular response. Main results. We observed the well-preserved heart rate and blood pressure control in patients with early stage of Parkinson disease. However, causal analysis of interactions between heart rate and blood pressure oscillations revealed subtle differences in baroreflex function and baroreflex mediated vasoconstriction response to orthostasis. Furthermore, a tendency towards a decreased contraction strength in Parkinson disease was observed. Significance. Considering only subtle cardiovascular control impairment in our study employing a wide array of sensitive methods at the time when motor signs were clearly expressed, we suggest that motor signs dominated in this stage of Parkinson disease.

Anti-neuroinflammation effect of zonisamide in early Parkinson’s disease: A chronological PET study (P13-11.010)

<h3>Objective:</h3> To evaluate the in vivo neuroprotective effect of zonisamide, we examined the chronological change in the microglial activation and nigrostriatal degeneration in the early stage of PD by using PET. <h3>Background:</h3> Neuroinflammation play a significant role in the pathology of Parkinson’s disease (PD). Previous animal and ex-vivo study suggested that zonisamide had beneficial effect against neuroinflammation. <h3>Design/Methods:</h3> Eleven early stage of PD patients and normal controls underwent [¹¹C] DPA713 PET and [¹¹C]CFT PET to assess microglial activation and dopamine transporter density. PD patients were divided into PD with and without zonisamide therapy. All patients were scanned annually for three years (four times per person). The binding potential (BP_ND) was estimated with simplified reference tissue model. Voxel wised SPM analysis and ROI analysis were used to compare the increase in [¹¹C] DPA713 BP_ND and [¹¹C]CFT SUVR between two groups. Local association between [¹¹C] DPA713 BP_ND and [¹¹C]CFT SUVR were evaluated with direct ROI analysis. <h3>Results:</h3> The PD group showed a significant increase in [¹¹C] DPA713 BP_ND in the whole brain predominantly in the parieto-occipital lobe. Increase in [¹¹C] DPA713 BP_ND was more broadly in the following scans. The [¹¹C] DPA713 BP_ND changes were smaller in the zonisamide+ group than in the zonisamide-therapy. Although [¹¹C]CFT SUVR showed chronological decrease in the striatum in all PD group, correlation analysis showed a positive direct correlation between [¹¹C]DPA713 BP_ND and [¹¹C]CFT SUVR in the putamen in the zonisamide+ group but not in the zonisamide-group. The seven series subtest in MMSE showed significant increase in the zonisamide+ group. <h3>Conclusions:</h3> Microglial activation is present especially over the parieto-occipital cortex even at an early stage of PD. Our in vivo study suggested that zonisamide might have the potential to suppress the neuroinflammation, induce the neuroprotective effect of microglia in the putamen, and beneficial effect on attention. <b>Disclosure:</b> The institution of Dr. Matsudaira has received research support from Sumitomo Pharma Co., Ltd. . Dr. Terada has nothing to disclose. Dr. Bunai has nothing to disclose. Prof. Hashizume has nothing to disclose. Dr. Yokokura has nothing to disclose. Dr. Takashima has nothing to disclose. Dr. KONISHI has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Eisai Co., Ltd. Dr. KONISHI has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Chugai Pharmaceutical Co., Ltd.. Dr. Obi has nothing to disclose. The institution of Prof. Ouchi has received research support from Sumitomo Pharma Co., Ltd.

Phase Ib Study Design Evaluating The Safety, Pharmacokinetics And Pharmacodynamics Of Selnoflast, A Novel NLRP3 Inflammasome Inhibitor In Early-Stage PD (P2-11.007)

Phase Ib Study Design Evaluating The Safety, Pharmacokinetics And Pharmacodynamics Of Selnoflast, A Novel NLRP3 Inflammasome Inhibitor In Early-Stage PD (P2-11.007)

Exploratory Delayed-Start Analysis Of PASADENA Part 3 52-Week OLE Evaluating Prasinezumab Efficacy On Motor Progression And Complications In Early-Stage PD (S32.005)

Exploratory Delayed-Start Analysis Of PASADENA Part 3 52-Week OLE Evaluating Prasinezumab Efficacy On Motor Progression And Complications In Early-Stage PD (S32.005)

Assessing the swallow tail sign in a real life scenario (P5-11.004)

<h3>Objective:</h3> To evaluate the accuracy of the swallow tail sign to differentiate between essential tremor (ET) and Parkinson’s disease (PD) in clinical practice. <h3>Background:</h3> The loss of the swallow tail sign (STS), a hyperintensity within the substantia nigra on high-resolution T2*/SWI brain MRI, is present in early stages of PD, and has been suggested as a diagnostic biomarker because of its high accuracy when evaluated by experienced neuroradiologists and with sequences with slice thickness under 1.5mm. In ET, the STS is preserved, so its evaluation could help differentiate it from PD. There are no studies that evaluate the accuracy of STS detection in clinical practice by a movement disorders neurologist using non-optimal MRI slice thickness. <h3>Design/Methods:</h3> Seventy-three 3T brain MRIs from patients who were clinically diagnosed with PD or ET were retrospectively assessed in a MacBook Pro using the software Horos by a movement disorders neurologist. In the SWAN sequence (0.68×0.68×2 mm3) five slices caudal to the upper limit of the red nucleus were selected and analyzed. The STS was assessed blindly on each side to define the PD diagnosis. Uncertainty about the presence/absence of the STS was also computed for each side. <h3>Results:</h3> The overall accuracy was 79.5%, with 86.2% sensitivity and 75.0% specificity. Interestingly, when considering only the cases where there were no uncertainties about the diagnosis based on STS presence/absence (29/73, 39.7%), the accuracy remained similar (79.3%) with a decrease in sensitivity and slight increase in specificity (76.9%, and 81.3% respectively). <h3>Conclusions:</h3> The visual assessment of the STS performed by a movement disorders neurologist in clinical practice yields good diagnostic accuracy to discriminate between ET and PD even with suboptimal image quality (slice thickness &gt;1.5mm). This supports the utility of this radiological sign in real life scenarios. <b>Disclosure:</b> Dr. Ruiz Yanzi has nothing to disclose. Dr. Matarazzo has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for International Parkinson and Movement Disorders Society. Mrs. NATERA-VILLALBA has received research support from Sociedad Española de Neurologia. Jose A Pineda-Pardo has nothing to disclose.

Gut-to-Brain α-Synuclein Transmission in Parkinson's Disease: Evidence for Prion-like Mechanisms.

Parkinson's disease (PD) is a multifactorial disorder involving both motor and non-motor symptoms caused by the progressive death of distinct neuronal populations, including dopaminergic neurons in the substantia nigra. The deposition of aggregated α-synuclein protein into Lewy body inclusions is a hallmark of the disorder, and α-synuclein pathology has been found in the enteric nervous system (ENS) of PD patients up to two decades prior to diagnosis. In combination with the high occurrence of gastrointestinal dysfunction in early stages of PD, current evidence strongly suggests that some forms of PD may originate in the gut. In this review, we discuss human studies that support ENS Lewy pathology as a characteristic feature of PD, and present evidence from humans and animal model systems that α-synuclein aggregation may follow a prion-like spreading cascade from enteric neurons, through the vagal nerve, and into the brain. Given the accessibility of the human gut to pharmacologic and dietary interventions, therapeutic strategies aimed at reducing pathological α-synuclein in the gastrointestinal tract hold significant promise for PD treatment.

The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study.

Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated. We aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment. Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively. Follow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = -0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004). Autonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis.

Cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in tremor-dominant Parkinson's disease.

Protein misfolding within specific brain regions is a common characteristic of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease (PD). Therefore, a common term often used for these disorders is "proteinopathy". Currently, there has been increasing attention toward the overlap of pathogenesis between proteinopathies. We aimed to explore the cross-sectional and longitudinal level of the CSF α-synuclein (α-syn), amyloid βeta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) in PD subjects with tremor dominant (TD) and a non-tremor dominant (nonTD) subtype from the Parkinson Progression Markers Initiative (PPMI). We enrolled 411 early-stage PD patients and 187 healthy controls (HCs) from the PPMI. We compared the level of CSF biomarkers at four time points including baseline, 6months, 1year, and 2years. To investigate longitudinal changes in CSF proteins within each group, we used linear mixed models. The level of CSF biomarkers was significantly lower in PD patients compared to HCs at any visit. Moreover, there was no statistically significant difference in the level of CSF α-syn, Aβ1-42, t-tau, and p-tau between PD-TD and PD-nonTD. Longitudinal analysis showed significant CSF α-syn reduction after one year from baseline in PD-TD patients (P = 0.047). Also, there was a significant reduction in the level of CSF Aβ1-42 after two years in PD-nonTD patients but not HCs and PD-TD (P = 0.033). Our results indicate that different patterns in longitudinal changes of CSF biomarkers could be due to different pathophysiological mechanisms involved in each PD motor subtype.

Pinpointing the precise stimulation targets for brain rehabilitation in early-stage Parkinson’s disease

BackgroundTranscranial magnetic stimulation (TMS) is increasingly used as a promising non-pharmacological treatment for Parkinson’s disease (PD). Scalp-to-cortex distance (SCD), as a key technical parameter of TMS, plays a critical role in determining the locations of treatment targets and corresponding dosage. Due to the discrepancies in TMS protocols, the optimal targets and head models have yet to be established in PD patients.ObjectiveTo investigate the SCDs of the most popular used targets in left dorsolateral prefrontal cortex (DLPFC) and quantify its impact on the TMS-induced electric fields (E-fields) in early-stage PD patients.MethodsStructural magnetic resonance imaging scans from PD patients (n = 47) and normal controls (n = 36) were drawn from the NEUROCON and Tao Wu datasets. SCD of left DLPFC was measured by Euclidean Distance in TMS Navigation system. The intensity and focality of SCD-dependent E-fields were examined and quantified using Finite Element Method.ResultsEarly-stage PD patients showed an increased SCDs, higher variances in the SCDs and SCD-dependent E-fields across the seven targets of left DLPFC than normal controls. The stimulation targets located on gyral crown had more focal and homogeneous E-fields. The SCD of left DLPFC had a better performance in differentiating early-stage PD patients than global cognition and other brain measures.ConclusionSCD and SCD-dependent E-fields could determine the optimal TMS treatment targets and may also be used as a novel marker to differentiate early-stage PD patients. Our findings have important implications for developing optimal TMS protocols and personalized dosimetry in real-world clinical practice.

The assessment of executive functions to test the integrity of the nigrostriatal network: A pilot study.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms. The latter mainly include affective, sleep, and cognitive deficits. Non-demented PD patients often demonstrate impairments in several executive domains following neuropsychological evaluation. The current pilot study aims at assessing the discriminatory power of the Frontal Assessment Battery-15 (FAB15) in differentiating (i) non-demented PD patients and healthy controls and (ii) PD patients with more and less pronounced motor symptoms. Thirty-nine non-demented early-stage PD patients in the "on" dopamine state (26 females, mean age = 64.51 years, SD = 6.47, mean disease duration = 5.49 years, SD = 2.28) and 39 healthy participants (24 females, mean age = 62.60 years, SD = 5.51) were included in the study. All participants completed the FAB15. Motor symptoms of PD patients were quantified via the Unified Parkinson's Disease Rating Scale-Part III (UPDRS-Part III) and Hoehn and Yahr staging scale (H&Y). The FAB15 score, adjusted according to normative data for sex, age, and education, proved to be sufficiently able to discriminate PD patients from healthy controls (AUC = 0.69 [95% CI 0.60-0.75], SE = 0.06, p = 0.04, optimal cutoff = 11.29). Conversely, the battery lacked sufficient discriminative capability to differentiate PD patients based on the severity of motor symptoms. The FAB15 may be a valid tool for distinguishing PD patients from healthy controls. However, it might be less sensitive in identifying clinical phenotypes characterized by visuospatial impairments resulting from posteroparietal and/or temporal dysfunctions. In line with previous evidence, the battery demonstrated to be not expendable in the clinical practice for monitoring the severity of PD-related motor symptoms.

Pink1-/- Rats Demonstrate Swallowing and Gastrointestinal Dysfunction in a Model of Prodromal Parkinson Disease.

Early motor and non-motor signs of Parkinson disease (PD) include dysphagia, gastrointestinal dysmotility, and constipation. However, because these often manifest prior to formal diagnosis, the study of PD-related swallow and GI dysfunction in early stages is difficult. To overcome this limitation, we used the Pink1-/- rat, a well-established early-onset genetic rat model of PD to assay swallowing and GI motility deficits. Thirty male rats were tested at 4months (Pink1-/- = 15, wildtype (WT) control = 15) and 6months (Pink1-/- = 7, WT = 6) of age; analogous to early-stage PD in humans. Videofluoroscopy of rats ingesting a peanut-butter-barium mixture was used to measure mastication rate and oropharyngeal and pharyngoesophageal bolus speeds. Abnormal swallowing behaviors were also quantified. A second experiment tracked barium contents through the stomach, small intestine, caecum, and colon at hours 0-6 post-barium gavage. Number and weight of fecal emissions over 24h were also collected. Compared to WTs, Pink1-/- rats showed slower mastication rates, slower pharyngoesophageal bolus speeds, and more abnormal swallowing behaviors. Pink1-/- rats demonstrated significantly delayed motility through the caecum and colon. Pink1-/- rats also had significantly lower fecal pellet count and higher fecal pellet weight after 24h at 6months of age. Results demonstrate that swallowing dysfunction occurs early in Pink1-/- rats. Delayed transit to the colon and constipation-like signs are also evident in this model. The presence of these early swallowing and GI deficits in Pink1-/- rats are analogous to those observed in human PD.

Functional and neuropathological changes induced by injection of distinct alpha-synuclein strains: A pilot study in non-human primates

The role of alpha-synuclein in Parkinson's disease has been heavily investigated since its discovery as a component of Lewy bodies. Recent rodent data demonstrate that alpha-synuclein strain structure is critical for differential propagation and toxicity.Based on these findings, we have compared, for the first time, in this pilot study, the capacity of two alpha-synuclein strains and patient-derived Lewy body extracts to model synucleinopathies after intra-putaminal injection in the non-human primate brain. Functional alterations triggered by these injections were evaluated in vivo using glucose positron emission tomography imaging. Post-mortem immunohistochemical and biochemical analyses were used to detect neuropathological alterations in the dopaminergic system and alpha-synuclein pathology propagation.In vivo results revealed a decrease in glucose metabolism more pronounced in alpha-synuclein strain-injected animals. Histology showed a decreased number of dopaminergic tyrosine hydroxylase-positive cells in the substantia nigra to different extents according to the inoculum used. Biochemistry revealed that alpha-synuclein-induced aggregation, phosphorylation, and propagation in different brain regions are strain-specific.Our findings show that distinct alpha-synuclein strains can induce specific patterns of synucleinopathy in the non-human primate, changes in the nigrostriatal pathway, and functional alterations that resemble early-stage Parkinson's disease.

A Systematic Review of the Usage of Rotigotine During Early and Advanced Stage Parkinson's.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This disease is difficult to diagnose since its symptoms are similar to those of the aging process. Those with PD have impaired motor control and function, dyskinesia, and tremors. To treat PD, drugs that enhance the amount of dopamine given to the brain are administered to alleviate symptoms. This inquiry examines the prescription of rotigotine to achieve this objective. The primary objective of thisreview is to examine the usage of rotigotine in both the late and early stages of PD. The statistical model utilized in the review found that there was not a significant difference in the dosage of rotigotine prescribed to late and early-stage PD patients, however, there were some confounding variables that may have skewed this result; therefore, further research is necessary to validate or nullify this hypothesis.

The Assessment of the Diagnostic Delay in Japanese People with Parkinson's Disease Using a Web-based Survey of Patients and Physicians.

Objective Although diagnostic criteria of Parkinson's disease (PD) have been established, the details of the process by which patients notice symptoms, visit a physician, and receive a diagnosis of PD is unclear. We therefore explored factors influencing latency in diagnosing PD. Methods We performed an internet-based survey of patients with PD and their families as well as physicians treating patients with PD to identify any diagnostic latency and its determinants. Evaluated factors included motor and non-motor symptoms, the diagnosis history and symptoms, patients' feelings toward PD prior to the diagnosis, and physician-determined reasons for the diagnostic delay. Results Among the 186 eligible patient respondents (including 87 responses from family members of patients), 24% received a PD diagnosis >1 year after the onset of PD-related symptoms, 58.6% had mid- or late-stage PD at the diagnosis, and 29% of patients had initially thought their symptoms were common age-related phenomena. Tremor (42%) was the most frequent symptom that led patients to visit a medical institution, whereas gait disturbance (14%) was the least frequent. More patients diagnosed with early-stage PD than those diagnosed with mid- or late-stage PD consulted a neurologist at their first visit. Among the 331 eligible physicians, patients' misinterpretation of their symptoms as being age-related was deemed one of or the most common cause (s) of a diagnostic delay by 67% and 36%, respectively. Conclusion Patients' insufficient or misinterpreted information about PD may cause delays in accessing healthcare services, leading to diagnostic delay.

Rate control deficits during pinch grip and ankle dorsiflexion in early-stage Parkinson's disease.

Much of our understanding of the deficits in force control in Parkinson's disease (PD) relies on findings in the upper extremity. Currently, there is a paucity of data pertaining to the effect of PD on lower limb force control. The purpose of this study was to concurrently evaluate upper- and lower-limb force control in early-stage PD and a group of age- and gender-matched healthy controls. Twenty individuals with PD and twenty-one healthy older adults participated in this study. Participants performed two visually guided, submaximal (15% of maximum voluntary contractions) isometric force tasks: a pinch grip task and an ankle dorsiflexion task. PD were tested on their more affected side and after overnight withdrawal from antiparkinsonian medication. The tested side in controls was randomized. Differences in force control capacity were assessed by manipulating speed-based and variability-based task parameters. Compared with controls, PD demonstrated slower rates of force development and force relaxation during the foot task, and a slower rate of relaxation during the hand task. Force variability was similar across groups but greater in the foot than in the hand in both PD and controls. Lower limb rate control deficits were greater in PD with more severe symptoms based on the Hoehn and Yahr stage. Together, these results provide quantitative evidence of an impaired capacity in PD to produce submaximal and rapid force across multiple effectors. Moreover, results suggest that force control deficits in the lower limb may become more severe with disease progression.

Relationship between [123I]FP-CIT SPECT data and peripheral CD4 + T cell profile in newly-diagnosed drug-naïve Parkinson's disease patients.

Dysregulation of the CD4 + T cell compartment occurs in Parkinson's Disease (PD). Nonetheless, the exact relationship with dopamine transporter (DAT) SPECT denervation patterns is currently unknown. Expression of transcription factors and levels of circulating CD4 + T cell subsets were assessed in peripheral blood mononuclear cells (PBMC) from 23 newly diagnosed drug-naïve PD patients. Semi-quantitative [123I]-FP-CIT SPECT data, i.e. uptake in the most and least affected putamen (maP, laP) and caudate (maC, laC), total striatal binding ratio (tSBR), and total putamen-to-caudate ratio (tP/C) were obtained. FOXP3 mRNA levels correlated with the uptake in maC (r = - 0.542, P = 0.011), laP (r = - 0.467, P = 0.033), and tSBR (r = - 0.483, P = 0.027). Concerning flow cytometry analysis of circulating CD4 + T cell subsets, a significant relationship between tP/C, caudate uptake, and the levels of both T helper (Th)1 and 2, was detected. Furthermore, we found significant correlations between the uptake in maP and the total count of naïve and activated T regulatory cells (Treg) (r = - 0.717, P = 0.001; r = - 0.691, P = 0.002), which were confirmed after the Benjamini-Hochberg correction for multiple comparisons using a false discovery rate at level q = 0.10. Levels of circulating naïve Treg were higher (P = 0.014) in patients with more extensive dopaminergic denervation, suggesting a compensatory phenomenon. Peripheral CD4 + T cell immunity is involved in early-stage PD and novel correlations with striatal DAT loss were observed.

Functional and structural alterations as diagnostic imaging markers for depression in de novo Parkinson's disease.

Depression in Parkinson's disease (PD) is identified and diagnosed with behavioral observations and neuropsychological measurements. Due to the large overlaps of depression and PD symptoms in clinical manifestations, it is challenging for neurologists to distinguish and diagnose depression in PD (DPD) in the early clinical stage of PD. The advancement in magnetic resonance imaging (MRI) technology provides potential clinical utility in the diagnosis of DPD. This study aimed to explore the alterations of functional and structural MRI in DPD to produce neuroimaging markers in discriminating DPD from non-depressed PD (NDPD) and healthy controls (HC). We recruited 20 DPD, 37 NDPD, and 41 HC matched in age, gender, and education years. The patients' diagnosis with PD was de novo. The differences in regional homogeneity (ReHo), voxel-wise degree centrality (DC), cortical thickness, cortical gray matter (GM) volumes, and subcortical GM volumes among these groups were detected, and the relationship between altered indicators and depression was analyzed. Moreover, the receiver operating characteristic (ROC) analysis was performed to assess the diagnostic efficacy of altered indicators for DPD. Compared to NDPD and HC, DPD showed significantly increased ReHo in left dorsolateral superior frontal gyrus (DSFG) and DC in left inferior temporal gyrus (ITG), and decreased GM volumes in left temporal lobe and right Amygdala. Among these altered indicators, ReHo value in left DSFG and DC values in left ITG and left DSFG were significantly correlated with the severity of depression in PD patients. Comparing DPD and NDPD, the ROC analysis revealed a better area under the curve value for the combination of ReHo value in left DSFG and DC value in left ITG, followed by each independent indicator. However, the difference is not statistically significant. This study demonstrates that both functional and structural impairments are present in DPD. Among them, ReHo value of left DSFG and DC value of left ITG are equally well suited for the diagnosis and differential diagnosis of DPD, with a combination of them being slightly preferable. The multimodal MRI technique represents a promising approach for the classification of subjects with PD.