Idiopathic Parkinson's Disease Research Articles

Co-Occurrence of Apathy and Impulse Control Disorders in Parkinson Disease: Variation across Multiple Measures.

To determine if the co-occurrence of apathy and impulse control disorders (ICDs) in Parkinson disease is dependent on instrument selection and assess the concurrent validity of three motivation measures by examining interrelationships between them. Ninety-seven cognitively normal individuals with idiopathic Parkinson disease (PD) completed the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease-Rating Scale (QUIP-RS) and three apathy measures: the Apathy Scale, Lille Apathy Rating Scale, and Item 4 of the Movement Disorder Society-Unified Parkinson Disease Rating Scale. Fifty (51.5%) participants were classified as apathetic on at least one measure, and only four individuals (4.3%) obtained clinically elevated scores on all three measures. The co-occurrence of apathy and ICD varied across measures. We observed a co-occurrence of apathy and ICDs in PD patients with each apathy instrument; however, limited concurrent validity exists across measures. This is important for future investigations into shared pathophysiology and the design of future clinical trials aimed at improving the early detection and treatment of these debilitating syndromes.

Oculomotor Dysfunction in Idiopathic and LRRK2-Parkinson's Disease and At-Risk Individuals.

Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD). To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2. The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests. We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy. iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers.

Subthalamic Nucleus Stimulation Modulates Cognitive Theory of Mind in Parkinson's Disease.

Theory of mind (ToM), the ability to infer others' mental state, is essential for social interaction among human beings. It has been widely reported that both cognitive (inference of knowledge) and affective (inference of emotion) components of ToM are disrupted in Parkinson's disease (PD). Previous studies usually focused on the involvement of the prefrontal cortex. This study investigated the causal role of the subthalamic nucleus (STN), a key hub of the fronto-basal ganglia loops, in ToM. Thirty-four patients with idiopathic PD (15 women, aged 62.2 ± 8.3 years) completed a Yoni task with deep brain stimulation (DBS) ON and OFF. The Yoni task was designed to separate the cognitive and affective components of ToM. Volumes of tissue activated (VTA) were computed for three subregions of the STN. DBS showed insignificant effects on ToM inference costs at the group level, which may be due to the large interindividual variability. The associative VTA correlated with the cognitive inference cost change but not the affective inference cost change. Patients with greater associative STN stimulation infer more slowly on cognitive ToM. Stimulating associative STN can adversely affect cognitive ToM in PD patients, especially in patients with a wide range of stimulation (≥0.157) or cognitive decline (Montreal Cognitive Assessment < 26). The associative STN plays a causal role in cognitive ToM in patients with PD. However, stimulating the associative STN likely impairs cognitive ToM and potentially leads to social interaction deficits in PD. © 2024 International Parkinson and Movement Disorder Society.

LRRK2 kinase inhibition protects against Parkinson's disease-associated environmental toxicants.

Idiopathic Parkinson's disease (PD) is epidemiologically linked with exposure to toxicants such as pesticides and solvents, which comprise a wide array of chemicals that pollute our environment. While most are structurally distinct, a common cellular target for their toxicity is mitochondrial dysfunction, a key pathological trigger involved in the selective vulnerability of dopaminergic neurons. We and others have shown that environmental mitochondrial toxicants such as the pesticides rotenone and paraquat, and the organic solvent trichloroethylene (TCE) appear to be influenced by the protein LRRK2, a genetic risk factor for PD. As LRRK2 mediates vesicular trafficking and influences endolysosomal function, we postulated that LRRK2 kinase activity may inhibit the autophagic removal of toxicant damaged mitochondria, resulting in elevated oxidative stress. Conversely, we suspected that inhibition of LRRK2, which has been shown to be protective against dopaminergic neurodegeneration caused by mitochondrial toxicants, would reduce the intracellular production of reactive oxygen species (ROS) and prevent mitochondrial toxicity from inducing cell death. To do this, we tested in vitro if genetic or pharmacologic inhibition of LRRK2 (MLi2) protected against ROS caused by four toxicants associated with PD risk - rotenone, paraquat, TCE, and tetrachloroethylene (PERC). In parallel, we assessed if LRRK2 inhibition with MLi2 could protect against TCE-induced toxicity in vivo, in a follow up study from our observation that TCE elevated LRRK2 kinase activity in the nigrostriatal tract of rats prior to dopaminergic neurodegeneration. We found that LRRK2 inhibition blocked toxicant-induced ROS and promoted mitophagy in vitro, and protected against dopaminergic neurodegeneration, neuroinflammation, and mitochondrial damage caused by TCE in vivo. We also found that cells with the LRRK2 G2019S mutation displayed exacerbated levels of toxicant induced ROS, but this was ameliorated by LRRK2 inhibition with MLi2. Collectively, these data support a role for LRRK2 in toxicant-induced mitochondrial dysfunction linked to PD risk through oxidative stress and the autophagic removal of damaged mitochondria.

Detection of elevated levels of PINK1 in plasma from patients with idiopathic Parkinson's disease.

Numerous lines of evidence support the intricate interplay between Parkinson's disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls. A total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls. PINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores. These findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.

Effects of focal muscle vibration on cervical pain in Parkinson's disease patients: a pilot study.

Musculoskeletal pain is a common symptom of Parkinson's disease (PD) that is not adequately treated with current dopaminergic drugs. This pilot study sought to investigate the effect of focal muscle vibration (fMV) on a group of Parkinson's disease patients suffering from chronic cervical pain. In addition to conventional physiotherapy, twenty-two patients with idiopathic Parkinson's disease (Hoehn and Yahr stages II-III) received three weeks of bilateral focal musclevibration to the trapezius muscles. The Visual Analogue Scale (VAS), the Short-form McGill, and the Present PainIntensity scales were used to assess pain at baseline (T0), after three weeks of treatment (T1), one week after the last treatment session (T2), and three weeks after T2 (T3). Pain intensity decreased significantly from baseline to T1 across all pain scales (p < 0.0001). Furthermore, the beneficial effect of fMV on cervical pain lasted up to one month after treatment. Our findings show that fMV, in combination with conventional physiotherapy, is effective at reducing pain intensity in PD patients, with results visible even after a month of follow-up.

Association between Religiousness and Quality of Life amongPatientsin Brazil diagnosed with Idiopathic Parkinson's Disease.

The importance of religiousness in idiopathic Parkinson's disease (IPD) has been the subject of conflicting research. The impact of religiousness on quality of life and depressive symptoms has also been poorly studied in this population. This study investigated the correlation between religiousness and quality of life in patients with IPD. We evaluated 37 patients with IPD(according to the criteria of the Movement Disorders Society)who werefrom an outpatient clinic specializing in movement disorders in Brazil. We assessed the patients using the Duke University Religion Index and scales for motor impairment, cognition, quality of life, and depression. Spearman's test was used to check for possible correlations between the different dimensions of religiousness and the clinical variables analyzed. Patients with a worse quality of life and more depressive symptoms showed greater intrinsic religiousness.

Mild cognitive impairment among LRRK2 and GBA1 patients with Parkinson's disease

BackgroundMild cognitive impairment (MCI) is common in Parkinson's disease (PD). We aimed to assess the incidence of MCI among patients with PD, carriers of mutations in LRRK2 and GBA1 genes, based on the movement disorder society (MDS) criteria for the diagnosis of MCI in early-stage PD. MethodsPatients with PD were included if they scored ≤2 on the Hoehn and Yahr and ≤6 years since motor symptom onset. A group of age and gender matched healthy adults served as controls. A neuropsychological cognitive battery was used covering five cognitive domains (executive functions, working memory, memory, visuospatial and language). MCI was explored while applying two methods (level I and II). Frequency of MCI was assessed in comparison between groups. Results70 patients with idiopathic PD (iPD) (68 % males), 42 patients with LRRK2-PD (61 % males), 83 patients with GBA1-PD (63 % males) and 132 age and gender matched controls (61 % males), participated in this study. PD groups were similar in clinical characteristics. Level I criteria were positive in 57.5 % of iPD, 43 % of LRRK2-PD and 63.4 % of the GBA1-PD (p = 0.071). Level II criteria was met by 39 % of iPD, 14 % LRRK2-PD and 41 % of GBA1-PD (p < 0.001), when using a 2 standard-deviation (SD) threshold. GBA1-PD and iPD showed impairments on multiple domains even in the more conservative 2 SD, reflecting MCI. ConclusionsThe majority of our PD cohort was classified as MCI when assessed with strict criteria. GBA1-PD and iPD showed a more widespread pattern of MCI compared with LRRK2-PD.

Free-Water Imaging of the Nucleus Basalis of Meynert in Patients With Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

Cognitive impairments are common in idiopathic REM sleep behavior disorder (iRBD), in which the cholinergic degeneration of nucleus basalis of Meynert (NBM) may play an important role. However, the progressive changes of NBM, the relationship between progressive NBM degeneration and progression of cognitive impairments, and whether degeneration of the NBM can predict cognitive decline in patients with iRBD remain unclear. This study aimed to investigate the cross-sectional and longitudinal microstructural alterations in the NBM of patients with iRBD using free-water imaging and whether free water in the NBM is related to cognitive, mood, and autonomic function. We compared the baseline free-water values in the NBM between 59 healthy controls (HCs), 57 patients with iRBD, 57 patients with Parkinson disease (PD) with normal cognition (PD-NC), and 64 patients with PD with cognitive impairment (PD-CI). Thirty patients with iRBD and 40 HCs had one longitudinal data. In patients with iRBD, we explored the associations between baseline and longitudinal changes of free-water values in the NBM and clinical characteristics and whether baseline free-water values in the NBM could predict cognitive decline. IRBD, PD-NC, and PD-CI groups had significantly increased free-water values in the NBM compared with HCs, whereas PD-CI had higher free-water values compared with iRBD and PD-NC. In patients with iRBD, free-water values in the NBM were progressively elevated over follow-up and correlated with the progression of cognitive impairment and depression. Free-water values in the NBM could predict cognitive decline in the iRBD group. Furthermore, we found that patients with iRBD with cognitive impairment had higher relative change of free-water value in the NBM compared with patients with iRBD with normal cognition over follow-up. This study proves that free-water values in the NBM are elevated cross-sectionally and longitudinally and are associated with the progression of cognitive impairment and depression in patients with iRBD. Moreover, the free-water value in the NBM can predict cognitive decline in patients with iRBD. Whether free-water imaging of the NBM has the potential to be a marker for monitoring progressive cognitive impairment and predicting the conversion to dementia in synucleinopathies needs further investigation.

Can Dance Improve Turning in People With Parkinson's Disease?

Objective: To investigate the effects of a dance intervention on selected functional parameters during the 180° turning phase of the Timed Up & Go (TUG) test in people with Parkinson's Disease (PwPD). Methods: Fifteen adults clinically diagnosed with idiopathic PD were allocated into dance intervention (DIG; n = 7 ; age 73 ± 2 years) and control (CG; n = 8; age 64 ± 5 years) groups. The dance intervention lasted for 3 months (1 hour, twice a week). At baseline, all participants completed the Unified PD Rating Scale-part III, the International Physical Activity Questionnaire-short form, and the Hoehn & Yahr scale. Pre- and post-intervention, the primary outcomes were measured (number of steps and time to complete the 180° turning phase of the TUG test) at 2 speeds (comfortable walking and as quickly and safely speed) while using the Xsens® 3D motion suit. The secondary outcome (girdle dissociation) was assessed by calculating the difference between pelvis and affected shoulder orientation in the transverse plane (dissociation angles) at each data point during the TUG test's 180° turning phase. Results: At participant's comfortable walking speed, the functionality during the 180° turning remained unaffected following the dance intervention. However, at participant's fast speed, the dance intervention group significantly reduced the number of steps with a large effect size, and the total time taken to complete the 180° turning with a medium effect size. Post-intervention, most participants in the dance intervention group reduced the affected shoulder and pelvic girdle dissociation and turned more "en bloc." Conclusion: Dance can improve selected functional parameters during the 180° turning at fast speed in PwPD. The current results should be considered in rehabilitation programs.

RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses

Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease. We did whole-exome sequencing in probands from families in Canada and Tunisia with Parkinson's disease without a genetic cause, who were recruited from the Centre for Applied Neurogenetics (Vancouver, BC, Canada), an international consortium that includes people with Parkinson's disease from 36 sites in 24 countries. 61 RAB GTPases were genetically screened, and candidate variants were genotyped in relatives of the probands to assess disease segregation by linkage analysis. Genotyping was also done to assess variant frequencies in individuals with idiopathic Parkinson's disease and controls, matched for age and sex, who were also from the Centre for Applied Neurogenetics but unrelated to the probands or each other. All participants were aged 18 years or older. The sequencing and genotyping findings were validated by case-control association analyses using bioinformatic data obtained from publicly available clinicogenomic databases (AMP-PD, GP2, and 100 000 Genomes Project) and a private German clinical diagnostic database (University of Tübingen). Clinical and pathological findings were summarised and haplotypes were determined. In-vitro studies were done to investigate protein interactions and enzyme activities. Between June 1, 2010, and May 31, 2017, 130 probands from Canada and Tunisia (47 [36%] female and 83 [64%] male; mean age 72·7 years [SD 11·7; range 38-96]; 109 White European ancestry, 18 north African, two east Asian, and one Hispanic] underwent whole-exome sequencing. 15 variants in RAB GTPase genes were identified, of which the RAB32 variant c.213C>G (Ser71Arg) cosegregated with autosomal dominant Parkinson's disease in three families (nine affected individuals; non-parametric linkage Z score=1·95; p=0·03). 2604 unrelated individuals with Parkinson's disease and 344 matched controls were additionally genotyped, and five more people originating from five countries (Canada, Italy, Poland, Turkey, and Tunisia) were identified with the RAB32 variant. From the database searches, in which 6043 individuals with Parkinson's disease and 62 549 controls were included, another eight individuals were identified with the RAB32 variant from four countries (Canada, Germany, UK, and USA). Overall, the association of RAB32 c.213C>G (Ser71Arg) with Parkinson's disease was significant (odds ratio [OR] 13·17, 95% CI 2·15-87·23; p=0·0055; I2=99·96%). In the people who had the variant, Parkinson's disease presented at age 54·6 years (SD 12·75, range 31-81, n=16), and two-thirds had a family history of parkinsonism. RAB32 Ser71Arg heterozygotes shared a common haplotype, although penetrance was incomplete. Findings in one individual at autopsy showed sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In functional studies, RAB32 Arg71 activated LRRK2 kinase to a level greater than RAB32 Ser71. RAB32 Ser71Arg is a novel genetic risk factor for Parkinson's disease, with reduced penetrance. The variant was found in individuals with Parkinson's disease from multiple ethnic groups, with the same haplotype. In-vitro assays show that RAB32 Arg71 activates LRRK2 kinase, which indicates that genetically distinct causes of familial parkinsonism share the same mechanism. The discovery of RAB32 Ser71Arg also suggests several genetically inherited causes of Parkinson's disease originated to control intracellular immunity. This shared aetiology should be considered in future translational research, while the global epidemiology of RAB32 Ser71Arg needs to be assessed to inform genetic counselling. National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson's, the Michael J Fox Foundation for Parkinson's Research, and the UK Medical Research Council.

Long-term follow-up study of SWEDD patients with mild parkinsonian signs

BackgroundWhether scan without evidence of dopaminergic deficit (SWEDD) can be a reliable indication of a clinical entity of Parkinson’s disease (PD) is controversial.ObjectiveTo evaluate the proportion of SWEDD patients with...

Hearing dysfunction heralds an increase in non-motor burden and a worse quality of life in Parkinson's disease: new insights from non-motor spectrum.

Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.

Diagnosing Parkinson’s disease and monitoring its progression: Biomarkers from combined GC-TOF MS and LC-MS/MS untargeted metabolomics

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with a poorly understood etiology. An accurate diagnosis of idiopathic PD remains challenging as misdiagnosis is common in routine clinical practice. Moreover, current therapeutics focus on symptomatic management rather than curing or slowing down disease progression. Therefore, identification of potential PD biomarkers and providing a better understanding of the underlying disease pathophysiology are urgent. Herein, hydrophilic interaction liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-TOF MS) based metabolomics approaches were used to profile the serum metabolome of 50 patients with different stages of idiopathic PD (early, mid and advanced) and 45 age-matched controls. Levels of 57 metabolites including cysteine-S-sulfate and N-acetyl tryptophan were significantly higher in patients with PD compared to controls, with lower amounts of additional 51 metabolites including vanillic acid, and N-acetylaspartic acid. Xanthines, including caffeine and its downstream metabolites, were lowered in patients with PD relative to controls indicating a potential role caffeine and its metabolites against neuronal damage. Seven metabolites, namely cysteine-S-sulfate, 1-methylxanthine, vanillic acid, N-acetylaspartic acid, 3-N-acetyl tryptophan, 5-methoxytryptophol, and 13-HODE yielded a ROC curve with a high classification accuracy (AUC 0.977). Comparison between different PD stages showed that cysteine-S-sulfate levels were significantly increasing with the advancement of PD stages while LPI 20:4 was significantly decreasing with disease progression. Our findings provide new biomarker candidates to assist in the diagnosis of PD and monitor its progression. Unusual metabolites like cysteine-S-sulfate might point to therapeutic targets that could enhance the development of novel PD treatments, such as NMDA antagonists.

A Case Report of Two Patients with Idiopathic Parkinson’s Disease Treated with Korean Medicine Treatment and Temporomandibular Joint Balancing Therapy

Parkinson’s disease (PD) is a chronic degenerative disorder of the central nervous system. It has no cure, but current treatments can relieve symptoms and maintain quality of life. As PD progresses, controlling its symptoms becomes difficult. Here, we present the treatment of two patients with idiopathic PD using traditional Korean medicine (TKM) and temporomandibular joint balancing therapy (TBT). We measured the progress of the two patients using the unified PD rating scale (UPDRS) and the Hoehn and Yahr (HY) scale. Combined treatment of TKM and TBT decreased the total UPDRS score from 52 to 26 after 21 days in case 1, while it decreased the total UPDRS score from 91 to 65 after 20 days in case 2. In both patients, the HY scale score was maintained at 3, and no adverse events were observed. Thus, the combined treatment of TKM and TBT can produce a treatment response in PD patients.

α-Synuclein Pathology in PRKN-Linked Parkinson's Disease: New Insights from a Blood-Based Seed Amplification Assay.

Pathogenic variants in PRKN cause early-onset Parkinson's disease (PD), while the role of alpha-synuclein in PRKN-PD remains uncertain. One study performed a blood-based alpha-synuclein seed amplification assay (SAA) in PRKN-PD, not detecting seed amplification in 17 PRKN-PD patients. By applying a methodologically different SAA focusing on neuron-derived extracellular vesicles, we demonstrated alpha-synuclein seed amplification in 8 of 13 PRKN-PD patients, challenging the view of PRKN-PD as a non-synucleinopathy. Moreover, we performed blinded replication of the neuron-derived extracellular vesicles-dependent SAA in idiopathic PD patients and healthy controls. In conclusion, blood-based neuron-derived extracellular vesicles-dependent SAA represents a promising biomarker to elucidate the underpinnings of (monogenic) PD. ANN NEUROL 2024.

Vestibular-evoked myogenic potential abnormalities in Parkinson's disease with freezing of gait.

Vestibular dysfunction is closely associated with the pathophysiology of Parkinson's disease (PD) accompanied by freezing of gait (FOG); however, evidence supporting this clinical association is lacking. Vestibular-evoked myogenic potentials (VEMPs) have been widely acknowledged as a crucial electrophysiological parameter in the clinical evaluation of vestibular function. The present study investigated the possible correlation of FOG occurrence with VEMP observations in patients diagnosed with PD. Altogether, 95 idiopathic PD patients were recruited into the present cross-sectional study. All patients underwent motor and non-motor assessments using serial scales. In addition, the electrophysiological vestibular evaluation was conducted, which included cervical (cVEMP) and ocular VEMP (oVEMP) assessments. Furthermore, the correlations of bilateral c/oVEMP absence with clinical phenotypes, especially FOG, among the PD patients were analyzed. Among the 95 patients with PD, 44 (46.3%) had bilateral oVEMP absence and 23 (24.2%) had bilateral cVEMP absence, respectively. The proportions of patients with bilateral oVEMP absence (77.8% vs 30.9%, p = 0.004) and bilateral cVEMP absence (44.4% vs 19.5%, p = 0.035) were higher in the patient group exhibiting FOG than in the group without FOG. Following the adjustment of confounding variables, bilateral oVEMP absence (OR = 8.544, p = 0.007), rather than bilateral cVEMP absence, was shown to independently predict FOG occurrence in patients with PD. The close correlation between bilateral oVEMP absence and FOG in PD patients sheds new light on the possible role of central vestibular/upper brainstem dysfunction in FOG development in patients with PD.

Quantifying cerebral blood flow changes using arterial spin labeling: A comparative study of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease

IntroductionIdiopathic rapid eye movement sleep behavior disorder (iRBD) and Parkinson's disease (PD) have been found to have changes in cerebral perfusion and overlap of some of the lesioned brain areas. However, a consensus regarding the specific location and diagnostic significance of these cerebral blood perfusion alternations remains elusive in both iRBD and PD. The present study evaluated the patterns of cerebral blood flow changes in iRBD and PD. Material and methodsA total of 59 right-handed subjects were enrolled, including 15 patients with iRBD, 20 patients with PD, and 24 healthy controls (HC). They were randomly divided into groups at a ratio of 4 to 1 for training and testing. A PASL sequence was employed to obtain quantitative cerebral blood flow (CBF) maps. The CBF values were calculated from these acquired maps. In addition, AutoGluon was employed to construct a classifier for CBF features selection and classification. An independent t-test was performed for CBF variations, with age and sex as nuisance variables. The performance of the feature was evaluated using receiver operating characteristic (ROC) curves. A significance level of P < 0.05 was considered significant. CBF in several brain regions, including the left median cingulate and paracingulate gyri and the right middle occipital gyrus (MOG), showed significant differences between PD and HC, demonstrating good classification performance. The combined model that integrates all features achieved even higher performance with an AUC of 0.9380. Additionally, CBF values in multiple brain regions, including the right MOG and the left angular gyrus, displayed significant differences between PD and iRBD. Particularly, CBF values in the left angular gyrus exhibited good performance in classifying PD and iRBD. The combined model achieved improved performance, with an AUC of 0.8533. No significant differences were found in brain regions when comparing CBF values between iRBD and HC subjects. ConclusionsASL-based quantitative CBF change features can offer reliable biomarkers to assist in the diagnosis of PD. Regarding the characteristic of CBF in the right MOG, it is anticipated to serve as an imaging biomarker for predicting the progression of iRBD to PD.

The Effect of Oropharyngeal Resting Tremor on Swallowing Function in a Clinical Cohort of People with Parkinson's Disease.

Parkinson's Disease (PD) is a progressive neurodegenerative disease, with hallmark symptomology typically consisting of tremor, bradykinesia, and rigidity. Though the classic "pill-rolling" rest tremor in the hand or upper limb are often the most salient, it can occur throughout the body including the lower limbs, jaw, face, or tongue. There have been investigations into other motor related phenomena potentially affecting swallow function in PwPD previously. However, there have been no investigations of how oropharyngeal resting tremor in structures such as the tongue or larynx explicitly affects swallowing physiology. A retrospective analysis of previously conducted VFSS on 34 patients diagnosed with idiopathic PD (IPD) was performed to examine how individuals that displayed resting tremor during VFSS (Tremor +) and those who did not (Tremor-) differ in swallowing function. Measures of swallowing function including timing intervals of key swallow events, post-swallow residue, and penetration-aspiration scale (PAS) scores were recorded, and key demographic information including time since diagnosis and medication status were extracted from the medical records available. Multivariate models were used to identify differences between tremor groups for timing intervals and post-swallow residue, and chi-squares were computed for differences in PAS score distribution by group and bolus. Sixty-eight percent (23/34) of this sample displayed oropharyngeal resting tremor in at least one structure during VFSS. There were no instances of other tremor types observed in this sample. All participants were taking medication to manage PD symptomology. Significant effects of tremor group were observed for swallow timing intervals related to airway closure (p < 0.001), post-swallow residue (p < 0.05), and swallow safety at the bolus level in the Tremor + group (p < 0.001). These results suggest that PwPD who present with resting tremor in oropharyngeal structures may manifest with different variations in swallowing physiology, including altered timings of swallow events, increased pharyngeal residue, and greater associations of airway invasion with thinner and larger volume boluses. This study highlights the need for substantially more research into how motor fluctuations and phenotypes of PwPD contribute to alterations in swallowing function.

Emotional atypical arousal ratings for unpleasant stimuli in patients with Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study. Following a clinical assessment, each participant was asked to evaluate the arousal and valence of affective visual stimuli, and response time was recorded. Disease-specific measures including the MDS Unified Parkinson's Disease Rating Scale (MDS UPDRS) and the Non-Motor Symptom Scale (NMSS) were also collected. PD patients exhibited higher arousal responses compared to HC for negative/unpleasant pictures (scoring 7.32 ± 0.88 vs 5.43 ± 2.06, p < 0.001). The arousal response to negative/unpleasant pictures was correlated with measures of non-motor burden in PD (MDS UPDRS I and NMSS, rho = 0.480 and p = 0.023, rho = 0.533 and p = 0.010, respectively). Impaired emotional processing characterizes PD patients with mild disease and is related to the non-motor symptom burden. Given the importance of emotional processing for the development and maintenance of close interpersonal relationship and for coping with specific medical situations, it is crucial to direct PD patients towards therapeutic interventions focused on the recognition and processing of emotions.