Group Of Parkinson's Disease Patients Research Articles

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery

BackgroundIn this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. MethodsA total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6–15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. ResultsFifty-nine patients’ datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. ConclusionsIntraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

Facial expressions and identities recognition in Parkinson disease

Parkinson's Disease (PD) is associated with motor and non-motor symptoms. Among the latter are deficits in matching, identification, and recognition of emotional facial expressions. On one hand, this deficit has been attributed to a dysfunction in emotion processing. Another explanation (which does not exclude the former) links this deficit with reduced facial expressiveness in these patients, which prevents them from properly understanding or embodying emotions. To disentangle the specific contribution of emotion comprehension and that of facial expression processing in PD's observed deficit with emotions we performed two experiments on non-emotional facial expressions. In Experiment 1, a group of PD patients and a group of Healthy Controls (HC) underwent a task of non-emotional expression recognition in faces of different identity and a task of identity recognition in faces with different expression. No differences were observed between the two groups in accuracies. In Experiment 2, PD patients and Healthy Controls underwent a task where they had to recognize the identity of faces encoded through a non-emotional facial expression, through a rigid head movement, or as neutral. Again, no group differences were observed. In none of the two experiments hypomimia scores had a specific effect on expression processing. We conclude that in PD patients the observed impairment with emotional expressions is likely due to a specific deficit for emotions to a greater extent than for facial expressivity processing.

The Analysis of relation to brain iron deposition of Parkinson’s Disease using Quantitative Susceptibility Mapping

Objectives: This study aimed to investigate the levels of brain iron deposition in Parkinson's disease (PD) patients using Quantitative Susceptibility Mapping (QSM) and to determine whether distinctions compared to the general population exist. Furthermore, we examined potential variations in iron deposition among different PD subtypes.Methods: Structural brain imaging was conducted on 75 participants at Gangdong Kyung Hee University Hospital between August 2017 and May 2020. PD patients were categorized into Tremor Dominant (TD) and Postural Instability and Gait Difficulty (PIGD) subtypes. Voxel-based morphometry and QSM were employed to compare voxel-wise magnetic susceptibility across the entire brain between Normal Controls (NC) and PD groups. Subsequently, QSM values were compared between TD and PIGD groups.Results: QSM values were compared among 46 PD patients and 23 normal controls, as well as between TD (n=22) and PIGD (n=24) groups. Voxel-based QSM analysis revealed no significant differences between groups. Similarly, ROI-based QSM analysis showed no significant distinctions.Conclusions: No significant variations were observed between the PD patient group, NC group, or PD subtypes. This study systematically compared QSM values across a broad range of brain regions potentially linked to PD pathology. Additionally, the subdivision of the PD group into TD and PIGD subtypes for QSM-based iron deposition analysis represents a meaningful and innovative approach.

Aberrations in temporal dynamics of cognitive processing induced by Parkinson’s disease and Levodopa

The motor symptoms of Parkinson's disease (PD) have been shown to significantly improve by Levodopa. However, despite the widespread adoption of Levodopa as a standard pharmaceutical drug for the treatment of PD, cognitive impairments linked to PD do not show visible improvement with Levodopa treatment. Furthermore, the neuronal and network mechanisms behind the PD-induced cognitive impairments are not clearly understood. In this work, we aim to explain these cognitive impairments, as well as the ones exacerbated by Levodopa, through examining the differential dynamic patterns of the phase-amplitude coupling (PAC) during cognitive functions. EEG data recorded in an auditory oddball task performed by a cohort consisting of controls and a group of PD patients during both on and off periods of Levodopa treatment were analyzed to derive the temporal dynamics of the PAC across the brain. We observed distinguishing patterns in the PAC dynamics, as an indicator of information binding, which can explain the slower cognitive processing associated with PD in the form of a latency in the PAC peak time. Thus, considering the high-level connections between the hippocampus, the posterior and prefrontal cortices established through the dorsal and ventral striatum acting as a modulatory system, we posit that the primary issue with cognitive impairments of PD, as well as Levodopa’s cognitive deficit side effects, can be attributed to the changes in temporal dynamics of dopamine release influencing the modulatory function of the striatum.

Stereotactic Staged Asymmetric Bilateral Radiofrequency Lesioning for Parkinson’s Disease

Introduction: Parkinson’s disease (PD) is one of the most common neurodegenerative progressive disorders. Despite the dominance of neurostimulation technology, stereotactic lesioning operations play a significant role in the treatment of PD. The aim of the study was to evaluate the effectiveness and safety of staged bilateral asymmetric radiofrequency (RF) stereotactic lesioning in a highly selected group of PD patients. Material and Methods: A retrospective review of 418 consecutive patients undergoing stereotactic ablation for advanced PD at our institution revealed 28 patients who underwent staged asymmetric bilateral ablation. In this subset, after initial RF thalamotomy, contralateral pallidotomy was performed in 16 (57.1%) patients (group Vim-GPi), and contralateral lesion of the subthalamic nucleus (STN) was performed in 12 (32.9%) patients (group Vim-STN). The mean duration of disease before the first surgery was 9.9 ± 0.8 years. The mean interval between the two operations was 3.5 ± 0.4 years (range, 1–10 years); in the Vim-GPi group, it was 3.1 ± 0.4 years; and in the Vim-STN group, it was 4.3 ± 0.1 years. After the second operation, the long-term follow-up lasted from 1 to 8 years (mean 4.8 ± 0.5 years). All patients were evaluated 1 year after the second operation. Results: One year after staged bilateral lesioning, the mean tremor score improved from baseline, prior to the first operation, from 19.8 to 3.8 (improvement of 81%), the overall mean rigidity score improved from 11.0 to 3.7 (improvement of 66%), and hypokinesia improved from 14.8 to 8.9 (improvement of 40%). One year after staged bilateral lesioning, the total UPDRS score improved in the Vim-GPi group by 47% in the OFF and 45.9% in the ON states. In the Vim-STN group, the total UPDRS score improved from baseline, prior to the first operation, by 44.8% in the OFF and 51.6% in the ON states. Overall, levodopa dose was reduced by 43.4%. Neurological complications were observed in 4 (14.3%) cases; among them, 1 (3.6%) patient had permanent events related to local ischemia after pallidotomy. Conclusion: Staged asymmetric bilateral stereotactic RF lesioning can be a safe and effective method in highly selected patients with advanced PD, particularly where deep brain stimulation is not available or desirable. Careful identification and selection of patients for ablative surgery allow achieving optimal results in the treatment of PD with bilateral symptoms.

Sexual dysfunction in a sample of Egyptian patients with Parkinson’s disease

BackgroundSexual dysfunction (SD) is a common, yet underdiagnosed problem in Parkinson Disease (PD) patients. It can negatively impact their quality of life (QoL) and clinical outcome. we tried to assess SD in a group of Egyptian PD patients.MethodsThe study is a case–control, cross-sectional study that included 200 participants, consisting of 100 PD patients and 100 matched healthy controls. Social, demographic information, and clinical variables were collected from both groups. Sexual functions were assessed using the Arabic Female Sexual Function Index (ArFSFI), and the Arabic version of International Index of Erectile Function (IIEF).ResultsWomen with PD scored worse on FSFI total score compared to controls (p < 0.001). Regarding the FSFI domains, they scored significantly lower in individual domains of desire (p < 0.001), arousal (p < 0.001), lubrication (p = 0.006), orgasm (p < 0.001), satisfaction (p < 0.001), and pain (p = 0.003), compared with controls. Men with PD scored worse on IIEF total scores compared to controls (p < 0.001). They showed significantly worse scores of erectile functions (p < 0.001), orgasmic function (p < 0.001), sexual desire (p < 0.001), intercourse satisfaction (p < 0.001), and overall satisfaction (p < 0.001). Both groups reported significant effect of SD on their QoL. There was a significant correlation between disease severity and SD.ConclusionSD is common in PD patients. It negatively impacts their QoL and partnership. Healthcare professionals should initiate conversations about SD with the patients and provide appropriate education and treatment options.

Impulse Control Disorders in the Polish Population of Patients with Parkinson's Disease.

Background and Objectives: Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. It is characterized by the presence of not only typical motor symptoms but also several less known and aware non-motor symptoms (NMS). The group of disorders included in the NMS is Impulse Control Disorders (ICDs). ICDs are a group of disorders in which patients are unable to resist temptations and feel a strong, pressing desire for specific activities such as gambling, hypersexuality, binge eating, and compulsive buying. The occurrence of ICDs is believed to be associated primarily with dopaminergic treatment, with the use of dopamine agonists (DA), and to a lesser extent with high doses of L-dopa. The aim of our study was to develop a profile of Polish ICDs patients and assess the frequency of occurrence of ICDs, as well as determine the risk factors associated with these disorders against the background of the PD population from other countries. Materials and Methods: Our prospective study included 135 patients with idiopathic PD who were hospitalized between 2020 and 2022 at the Neurological Department of University Central Hospital in Katowice. In the assessment of ICDs, we used the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). Other scales with which we assessed patients with PD were as follows: MDS-UPDRS part III and modified Hoehn-Yahr staging. Clinical data on age, gender, disease duration and onset, motor complications, and medications were collected from electronic records. Results: ICDs were detected in 27.41% of PD patients (binge eating in 12.59%, hypersexuality in 11.11%, compulsive buying in 10.37%, and pathological gambling occurred in only 5.19% of patients. In total, 8.89% had two or more ICDs). The major finding was that ICDs were more common in patients taking DA than in those who did not use medication from this group (83.78% vs. 54.07%, respectively; p = 0.0015). Patients with ICDs had longer disease duration, the presence of motor complications, and sleep disorders. An important finding was also a very low detection of ICDs in a routine medical examination; only 13.51% of all patients with ICDs had a positive medical history of this disorder. Conclusions: ICDs are relatively common in the population of Polish PD patients. The risk factors for developing ICDs include longer duration of the disease, presence of motor complications, sleep disorders, and use of DA and L-dopa. Due to the low detectability of ICDs in routine medical history, it is essential for physicians to pay more attention to the possibility of the occurrence of these symptoms, especially in patients with several risk factors. Further prospective studies on a larger group of PD patients are needed to establish a full profile of Polish PD patients with ICDs.

Epworth sleepiness scale is associated with increased striatal dopamine uptake in Parkinson's disease: a cross-sectional study.

A cross-sectional study was designed to investigate the possible association between Epworth sleepiness scale (ESS) scores and striatal dopamine uptake in the early stages of Parkinson's disease (PD). Two groups of PD patients (n = 464) and healthy controls (HC) (n = 162) were enrolled in the current study from the Parkinson's progression markers initiative cohort ( https://www.ppmi-info.org ). All the subjects were evaluated for excessive daytime sleepiness (EDS) using the ESS. They also completed specific measures to be assessed for motor and non-motor symptoms, including cognitive, gait, autonomic, and olfactory dysfunction. Dopamine transporter (DaT) scans were used to identify dopamine transporter impairments. Spatial normalization for DaTscan imaging of participants was performed to reach consistent orientation. A significant correlation was found between ESS score and right putamen (P < 0.001; correlation coefficient = 0.186) and left putamen (P = 0.003; correlation coefficient = 0.139) dopamine uptake in PD patients. The same results were revealed after adjusted Pearson's correlation for the effects of handedness, age, gender, and education. No significant correlation was found between the ESS score and the amount of caudate nucleus dopamine uptake in PD patients. Moreover, there was a significant association between caudate nucleus dopamine uptake and ESS score in neither PD patients nor HCs. The results of our study suggest that increased dopaminergic function of putamen nuclei may be associated with ESS scores in the early stages of PD. Further studies are needed at different PD stages and evaluate PD progression as a possible confounder.

Altered Functional Connectivity of the Subthalamic Nucleus in Parkinson's Disease: Focus on Candidates for Deep Brain Stimulation.

The hypothesis that the effectiveness of deep brain stimulation (DBS) in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of stimulation and other brain regions is growing. To investigate how the subthalamic nucleus (STN), the most frequently used DBS target for PD, is functionally linked to other brain regions in PD patients according to DBS eligibility. Clinical data and resting-state functional MRI were acquired from 60 PD patients and 60 age- and sex-matched healthy subjects within an ongoing longitudinal project. PD patients were divided into 19 patients eligible for DBS and 41 non-candidates. Bilateral STN were selected as regions of interest and a seed-based functional MRI connectivity analysis was performed. A decreased functional connectivity between STN and sensorimotor cortex in both PD patient groups compared to controls was found. Whereas an increased functional connectivity between STN and thalamus was found in PD patient groups relative to controls. Candidates for DBS showed a decreased functional connectivity between bilateral STN and bilateral sensorimotor areas relative to non-candidates. In patients eligible for DBS, a weaker STN functional connectivity with left supramarginal and angular gyri was related with a more severe rigidity and bradykinesia whereas a higher connectivity between STN and cerebellum/pons was related to poorer tremor score. Our results suggest that functional connectivity of STN varies among PD patients eligible or not for DBS. Future studies would confirm whether DBS modulates and restores functional connectivity between STN and sensorimotor areas in treated patients.

Environmental and genetic risk factors for Parkinson’s disease

Aim. To analyze risk factors in the group of patients with Parkinson’s disease (PD) and compare them with the literature data.Materials and methods. The study included 439 patients with PD and 354 controls, comparable by gender and age. For each individual, a registration card was filled in containing demographic, epidemiological, clinical, and neuropsychological data. The severity of the disease was studied according to the MDS-UPDRS scale; the stage of PD was determined according to the Hoehn and Yahr scale. Cognitive functions were assessed by the MoCA test and MMSE. The length of the (CAG)n repeat region in the HTT gene was determined using fragment analysis on the ABI 3730 DNA analyzer. The obtained results were analyzed using GeneMapper Software v4.1 (Applied Biosystems, USA).Results. When comparing patients with PD and the control group, the odds ratio (OR) for PD in individuals with traumatic brain injury was 3.13 (95% confidence interval (CI): 2,27–4.34; p = 4.94 × 10–13), which showed the significance of this risk factor for PD. Consumption of coffee in the anamnesis distinguished the group of PD patients from the control group (OR = 0.41 (95% CI: 0.30–0.56); p &lt; 0.0001), confirming its neuroprotective effect. Analysis of the variability in the length of the (CAG)n repeat regions in the HTT gene showed that patients whose genotype contained an allele with 17 repeats in combination with any allele other than an allele containing 18 repeats had a protective effect (OR = 0.50 (95% CI: 0.27–0.92); p = 0.025). All genotypes containing an allele with 18 repeats were predisposed to PD (OR = 2.57 (95% CI: 1.66–4.28); p = 0.007). The predisposing effect of the allele to PD, unrelated to the expansion of CAG repeats in the HTT gene, was revealed for the first time.Conclusion. Traumatic brain injury and the allele with 18 CAG repeats in the HTT gene are risk factors for PD. Coffee consumption can be attributed to protective factors in relation to PD.

Striatal Subregion Analysis Associated with REM Sleep Behavior Disorder in Parkinson's Disease.

REM sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with characteristic clinical subtypes and prognosis. In addition, nigrostriatal pathway, the most vulnerable anatomical area in PD, formed neuronal network interplaying with cortical and subcortical structures, and which may cause PD clinical phenotype. We evaluated the regional selectivity of presynaptic striatal dopaminergic denervation associated with RBD in PD. We compared two groups (n = 16) of PD patients with and without RBD in terms of specific binding ratios (SBR) in subregions of the striatum, which were measured using positron emission tomography with 18F-FP-CIT. SBRs of the anterior and posterior caudate, ventral striatum, and posterior and ventral putamen regions were measured in more or less affected side, and right or left side, or bilateral sum of the striatum. Age, disease duration, and severity of parkinsonism were not significantly different between groups. Although group differences in all areas were not significant with multiple comparison corrections, SBR of the ventral striatum and anterior caudate in sum of both sides was significantly less in the RBD than in the non-RBD group without correction (p < 0.05). In the right anterior caudate and left ventral striatum, SBR was also lower in the RBD than in the non-RBD group without correction (p < 0.05). Attention function was impaired in the RBD group compared with the non-RBD group (p < 0.05). However, these statistical significances were not definite after correction of multiple comparisons (p > 0.05). There is a possibility that RBD in early PD may be associated with presynaptic dopaminergic denervation in the ventral striatum and anterior caudate, which may explain decreased attention in our RBD group. RBD in PD may imply a distinct pathological progression. However, further study using large numbers of participants or longitudinal observation is necessary for the statistical conclusion because of small sample size.

Life events and the onset of motor symptoms in Parkinson's disease

BackgroundWhether there may be any relationship between stressful or traumatic life events (LE) and the subsequent motor symptoms onset in Parkinson's disease (PD) is still controversial. ObjectivesTo explore whether a subjectively perceived as stressful or traumatic LE were more frequently present in a group of recent motor onset parkinsonian patients (Recent Onset Parkinsonism - ROP) compared with healthy controls (HC) and a group of patients already diagnosed as PD. MethodsA consecutive series of 139 ROP patients, 138 matched PD patients and 138 HC were pooled through a validated LE exposure questionnaire evaluating the number of patients affected by LE and the amount of LE per group occurred in the last year, segregating by subjective severity in total and severe LE. ResultsThere was no significant difference in the percentage of patients affected by total (p = 0.134) nor by severe (p = 0.133) LE within the 3 groups. No significant difference was observed in the number of total LE between ROP and HC (p = 0.063), ROP and PD (p = 0.688), nor in severe LE (ROP vs. HC, p = 0.637. ROP vs. PD, p = 0.500). ConclusionsDuring the year of parkinsonian motor symptoms onset, the number of ROP patients exposed to total or severe LE or the amount of total or severe LE suffered by ROP were not significantly different to the group of PD patients or HC. A casual relationship between LE and the onset of motor symptoms in parkinsonian patients may be suggested.

Chronic Pain And Levodopa Therapy in Parkinson’s Disease Patients

Background: Pain is a frequent non-motor symptom in patients with Parkinson’s disease (PD) and appears to be related to low levels of dopamine. This study describes the characteristics of chronic pain in a group of PD patients undergoing levodopa therapy. Methods: This was a cross-sectional study. The pain was assessed in 21 selected PD patients with chronic pain using several scales and instruments. Changes in pain response from levodopa use (wearing-off phenomenon) were monitored. Results: The most prevalent type of pain was nociceptive (71.4%), musculoskeletal and dystonic, but neuropathic pain accounted for the highest pain score according to the Parkinson’s Disease Pain Classification System (45.5±30.08). Patients with neuropathic, nociplastic, or nociceptive pain upon wearing-off were those who responded to levodopa (p=0.999). According to the McGill questionnaire, patients with pain upon wearing-off had higher scores in the affective/motivational dimension (p=0.022). Conclusion: Using a new pain classification and scoring tool, this study corroborates a good response to levodopa in PD-related pain.

Assessing the interaction between L-dopa and γ-transcranial alternating current stimulation effects on primary motor cortex plasticity in Parkinson's disease.

L-dopa variably influences transcranial magnetic stimulation (TMS) parameters of motor cortex (M1) excitability and plasticity in Parkinson's disease (PD). In patients OFF dopaminergic medication, impaired M1 plasticity and defective GABA-A-ergic inhibition can be restored by boosting gamma (γ) oscillations via transcranial alternating current stimulation (tACS) during intermittent theta-burst stimulation (iTBS). However, it is unknown whether L-dopa modifies the beneficial effects of iTBS-γ-tACS on M1 in PD. In this study, a PD patients group underwent combined iTBS-γ-tACS and iTBS-sham-tACS, each performed both OFF and ON dopaminergic therapy (four sessions in total). Motor evoked potentials (MEPs) elicited by single TMS pulses and short-interval intracortical inhibition (SICI) were assessed before and after iTBS-tACS. We also evaluated possible SICI changes during γ-tACS delivered alone in OFF and ON conditions. The amplitude of MEP elicited by single TMS pulses and the degree of SICI inhibition significantly increased after iTBS-γ-tACS. The amount of change produced by iTBS-γ-tACS was similar in patients OFF and ON therapy. Finally, γ-tACS (delivered alone) modulated SICI during stimulation and this effect did not depend on the dopaminergic condition of patients. In conclusion, boosting cortical γ oscillatory activity via tACS during iTBS improved M1 plasticity and enhanced GABA-A-ergic transmission in PD patients to the same extent regardless of dopaminergic state. These results suggest a lack of interaction between L-dopa and γ-tACS effects at the M1 level. The possible neural substrate underlying iTBS-γ tACS effects, that is, γ-resonant GABA-A-ergic interneurons activity, may explain our findings.

Gray matter, white matter and cerebrospinal fluid abnormalities in Parkinson's disease: A voxel-based morphometry study.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by bradykinesia, tremor, and rigidity among other symptoms. With a 70% cumulative prevalence of dementia in PD, cognitive impairment and neuropsychiatric symptoms are frequent. In this study, we looked at anatomical brain differences between groups of patients and controls. A total of 138 people with PD were compared to 64 age-matched healthy people using voxel-based morphometry (VBM). VBM is a fully automated technique that allows for the identification of regional differences in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) allowing for an objective comparison of brains of different groups of people. We used statistical parametric mapping for image processing and statistical analysis. In comparison to controls, PD patients had lower GM volumes in the left middle cingulate, left lingual gyrus, right calcarine and left fusiform gyrus, also PD patients indicated lower WM volumes in the right middle cingulate, left lingual gyrus, right calcarine, and left inferior occipital gyrus. Moreover, PD patients group demonstrated higher CSF in the left caudate compared to the controls. Physical fragility and cognitive impairments in PD may be detected more easily if anatomical abnormalities to the cingulate gyrus, occipital lobe and the level of CSF in the caudate are identified. Thus, our findings shed light on the role of the brain in PD and may aid in a better understanding of the events that occur in PD patients.

High PSQI score is associated with the development of dyskinesia in Parkinson’s disease

Dyskinesia is one of the most disabling motor complications in Parkinson’s Disease (PD). Sleep is crucial to keep neural circuit homeostasis, and PD patients often suffer from sleep disturbance. However, few prospective studies have been conducted to investigate the association of sleep quality with dyskinesia in PD. The objective of the current study is to investigate the association between sleep quality and dyskinesia and build a prediction model for dyskinesia in PD. We prospectively followed a group of PD patients without dyskinesia at baseline for a maximum of 36 months. Univariable and multivariable Cox regression with stepwise variable selection was used to investigate risk factors for dyskinesia. The performance of the model was assessed by the time-dependent area under the receiver-operating characteristic curve (AUC). At the end of follow-up, 32.8% of patients developed dyskinesia. Patients with bad sleep quality had a significantly higher proportion of dyskinesia compared with those with good sleep quality (48.1% vs. 20.6%, p = 0.023). Multivariable Cox regression selected duration of PD, sleep quality, cognition, mood, and levodopa dose. Notably, high Pittsburgh sleep quality index (PSQI) score was independently associated with an increased risk of dyskinesia (HR = 2.96, 95% CI 1.05–8.35, p = 0.041). The model achieved a good discriminative ability, with the highest AUC being 0.83 at 35 months. Our results indicated that high PSQI score may increase the risk of developing dyskinesia in PD, implying that therapeutic intervention targeting improving sleep quality may be a promising approach to prevent or delay the development of dyskinesia in PD.

Impaired interhemispheric synchrony in Parkinson's disease patients with apathy

BackgroundApathy is a common non-motor symptom in Parkinson's disease (PD), yet the neural mechanism remains unknown. It has been reported that the lateralization of dopamine levels is correlated with apathetic symptoms. We aimed to ascertain the role of lateralization in the neuropathogenesis of apathy in PD. MethodsTwenty-six apathetic PD patients (PD-A), twenty-seven nonapathetic PD patients (PD-NA), and twenty-three healthy controls (HCs) were recruited. All subjects underwent T1-weighted and resting state functional MRI scanning during OFF medication state. Voxel-mirrored Homotopic Connectivity (VMHC) and asymmetry voxel-based morphometry (asymmetry VBM) analysis were applied to detect the synchrony of homotopic connections between hemispheres and grey matter asymmetry index. ResultsCompared with both PD-NA and HCs groups, the PD-A group showed excessively decreased z-VMHC values in the nucleus accumbens (NAcc) and putamen. Additionally, both PD subgroups exhibited decreased z-VMHC values in the cerebellum lobule VIII compared with controls. However, no corresponding alteration in grey matter asymmetry index was found. Further, a negative correlation between the z-VMHC values of the NAcc and the Apathy Scale (AS) was confirmed in the PD-A group. Meanwhile, the same relationship was also confirmed between the putamen and AS. Notably, ROC curve analyses uncovered that the z-VMHC values of the NAcc and putamen could be a potential neuroimaging feature discerning apathetic PD patient, respectively. LimitationsThis is a cross-sectional study. ConclusionOur findings demonstrated that the asymmetric functional connectivity in the mesocorticolimbic and nigrostriatal systems might induce the pathophysiological mechanisms of apathy in PD.

Atypical antipsychotic use and mortality risk in Parkinson disease

IntroductionDopamine receptor blocking atypical antipsychotic (DRB-AAP) use has previously been associated with increased adverse effects and mortality risk among persons with Parkinson disease (PD). Pimavanserin, the only AAP indicated for PD psychosis in the U.S., is a serotonin receptor inverse agonist/antagonist with no known DRB activity. Early observational data have reported inconsistent findings regarding mortality risk associated with pimavanserin. The objective of this study was to estimate all-cause mortality risks of pimavanserin as compared to DRB-AAPs. MethodsWe conducted a retrospective cohort study using a large U.S. commercial insurance database. Cox proportional hazards models were used to compare all-cause mortality risks between propensity score-matched groups of PD patients who were new users of pimavanserin or a DRB-AAP, further dividing DRB-AAPs into preferred (quetiapine, clozapine) and non-preferred (other remaining AAPs). ResultsWe identified 775, 4,563, and 1,297 individuals on pimavanserin, preferred, and non-preferred DRB-AAPs, respectively. There was no difference in mortality risk for pimavanserin vs. preferred DRB-AAPs [adjusted hazard ratio (aHR) 0.99, 95% CI: 0.81–1.20], or pimavanserin vs. non-preferred DRB-AAPs (aHR 0.98, 95% CI: 0.79–1.22) in intention-to-treat analyses. ConclusionMortality risk among PD patients using AAPs did not differ by antipsychotic drug categorization based on mechanism of action. Research on the comparative efficacy and morbidity of AAPs, and the mortality associated with psychosis itself is needed to guide clinical decision-making in the PD population.

Depotentiation of associative plasticity is intact in Parkinson's disease with mild dyskinesia

ObjectiveDepotentiation of homosynaptic plasticity of the primary motor cortex (M1) is impaired in patients with Parkinson's disease (PD) who have developed dyskinesias. In this exploratory study, we tested whether this holds true for heterosynaptic plasticity induced by paired associative stimulation (PAS). MethodsDyskinetic (n=11) and Non-dyskinetic (n=11), levodopa-treated PD patients were tested in M1 with PAS25ms alone, PAS25ms preceded by continuous theta-burst stimulation of the cerebellum (cTBSCB-PAS) as a method to evoke a larger plastic response in M1, and each of these two interventions followed by a depotentiation protocol (cTBS150pulses) to M1. ResultsPAS25ms and cTBSCB-PAS25ms induced long-term potentiation (LTP)-like responses in both groups of PD patients, with cTBSCB significantly boosting the plastic response. Both these LTP-like responses could be depotentiated by cTBS150, in both groups of patients. ConclusionsCerebellar stimulation enhances heterosynaptic plasticity in PD irrespective of dyskinesias. Depotentiation mechanisms of heterosynaptic plasticity are preserved in PD patients, including those with dyskinesias. The lack of depotentiation of LTP-like plasticity as a hallmark of dyskinesia in PD patients is not absolute. The ability to depotentiate LTP-like plasticity may potentially depend on the type of plasticity induced (homosynaptic or heterosynaptic), the circuits involved in these responses and the adequacy of dopaminergic stimulation.

Parkinson's Disease Symptoms Associated with Developing On-State Axial Symptoms Early after Subthalamic Deep Brain Stimulation.

Background: The relationship between axial symptoms in Parkinson’s disease (PD) and subthalamic deep brain stimulation (STN-DBS) is still unclear. Purpose: We searched for particular clinical characteristics before STN-DBS linked to on-state axial problems after surgery. Methods: We retrospectively analyzed baseline motor, emotional and cognitive features from PD patients with early axial symptoms (within 4 years after STN-DBS) and late axial symptoms (after 4 years). We also considered a group of PD patients without axial symptoms for at least 4 years after surgery. Results: At baseline, early-axial PD patients (n = 28) had a higher on-state Unified Parkinson’s Disease Rating Scale III (15.0 ± 5.6 to 11.6 ± 6.2, p = 0.020), higher axial score (2.4 ± 1.8 to 0.7 ± 1.0, p < 0.001) and worse dopaminergic response (0.62 ± 0.12 to 0.70 ± 0.11, p = 0.005), than non-axial PD patients (n = 51). Early-axial PD patients had short-term recall impairment, not seen in non-axial PD (36.3 ± 7.6 to 40.3 ± 9.3, p = 0.041). These variables were similar between late-axial PD (n = 18) and non-axial PD, but late-axial PD showed worse frontal dysfunction. Conclusions: PD patients with early axial symptoms after DBS may have a significantly worse presurgical motor phenotype, poorer dopaminergic response and memory impairment. This may correspond to a more severe form of PD.