Parkinson's Disease Duration Research Articles

Thalamic Dorsomedial Nucleus Free Water Correlates with Cognitive Decline in Parkinson's Disease.

Brain diffusion tensor imaging (DTI) has been shown to reflect cognitive changes in early Parkinson's disease (PD) but the diffusion-based measure free water (FW) has not been previously assessed. To assess if FW in the thalamic nuclei primarily involved with cognition (ie, the dorsomedial [DMN] and anterior [AN] nuclei), the nucleus basalis of Meynert (nbM), and the hippocampus correlates with and is associated with longitudinal cognitive decline and distinguishes cognitive status at baseline in early PD. Also, to explore how FW compares with conventional DTI, FW-corrected DTI, and volumetric assessments for these outcomes. Imaging data and Montreal Cognitive Assessment (MoCA) scores from the Parkinson's Progression Markers Initiative database were analyzed using partial correlations and ANCOVA. Primary outcome multiple comparisons were corrected for false discovery rate (q value). Thalamic DMN FW changes over 1year correlated with MoCA changes over both 1 and 3 years (partial correlations -0.222, q = 0.040, n = 130; and - 0.229, q = 0.040, n = 123, respectively; mean PD duration at baseline = 6.85months). NbM FW changes over 1 year only correlated with MoCA changes over 3 years (-0.222, q = 0.040). Baseline hippocampal FW was associated with cognitive impairment at 3 years (q = 0.040) and baseline nbM FW distinguished PD-normal cognition (MoCA ≥26) from PD-cognitive impairment (MoCA ≤25), (q = 0.008). The exploratory comparisons showed FW to be the most robust assessment modality for all outcomes. Thalamic DMN FW is a promising cognition progression biomarker in early PD that may assist in identifying cognition protective therapies in clinical trials. FW is a robust assessment modality for these outcomes. © 2021 International Parkinson and Movement Disorder Society.

Factors correlated with therapeutic effects of globus pallidus deep brain stimulation on freezing of gait in advanced Parkinson's disease: A pilot study

IntroductionDeep brain stimulation (DBS) has showed variable therapeutic effect on freezing of gait (FOG) in Parkinson's disease (PD). It is unclear which factors associated with the effect of DBS on FOG in patients with advanced PD. In this study, we investigated the correlation of pre and postoperative factors with the therapeutic effect of globus pallidus interna (GPi) DBS on FOG in PD patients. MethodsWe retrospectively analyzed PD patients with FOG (N = 20) who underwent GPi DBS surgery. Postoperatively, video-based analysis for FOG severity was performed at the first DBS programming and patients were categorized into two groups according to DBS effect on FOG (11 FOG responders and 9 FOG non-responders) at medication-off state. We analyzed preoperative clinical characteristics, cognitive function, striatal dopamine transporter availability, postoperative DBS programming parameters, lead locations, and volume of tissue activated in functional subregions of GPi. Bootstrap enhanced Elastic-Net logistic regression was used to select pre and postoperative factors associated with the effect of GPi DBS. ResultsTherapeutic effect of GPi DBS on FOG were correlated with the disease duration of PD before DBS surgery, preoperative improvement in FOG severity by levodopa medication, and the distance from active contact of DBS electrode to the prefrontal region of GPi anatomical site. ConclusionsOur study results suggest that the effect of GPi DBS on FOG is correlated with disease duration, levodopa responsiveness on FOG before DBS surgery and DBS electrode location, providing useful information to predict FOG outcome after GPi DBS in PD patients.

Seroprevalence of Toxoplasma Gondii in Parkinson’s Disease Iraqi Patients

Background Several studies have addressed the prevalence of Toxoplasma gondii (T. gondii), among Parkinson’s disease (PD) patients in different countries, and the potential association between the infection and PD; the results of these studies were conflicting. The study aims to investigate the prevalence of Toxoplasma infection among sample of Iraqi PD patients. Also, to examine the potential association of age, PD duration, gender, smoking habit, zone of residence and family history of PD, with the prevalence of Toxoplasma infection in PD patients.
 Patients and Methods Seventy-four PD patients attaining Dr. Saad Al-Witry Neuroscience Hospital in Baghdad/ Iraq for routine follow up, from different Iraqi governorates, were enrolled in this cross-sectional study. Detection of T. gondii was performed by detection of anti-Toxoplasma IgG and IgM antibodies in serum by ELISA method.
 Results The frequency rate of anti-Toxoplasma IgG antibodies in Iraqi PD patients was 43.2% (32/74); while, none of the participants was seropositive for anti-Toxoplasma IgM antibody. Age, PD duration, smoking habit and zone of residences were not shown to be risk factors for Toxoplasma infection in PD patients (P>0.05); meanwhile, female gender and positive family history of PD were shown to have a protective effect ((OR, 0.309; 95% CI, 0.099-0.966; P= 0.043) and (OR, 0.162; 95% CI, 0.037-0.705; P=0.015); respectively).
 Conclusions
 The prevalence rate of Toxoplasma infection in Iraqi PD patients is 43.2%, female gender and positive family history of PD might protect against Toxoplasma infection in PD patients.
 Key words: Iraq, Neurodegeneration, Parkinson’s disease, Prevalence, Toxoplasma gondii

Validation of the Chinese Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease.

Background: Impulse control and related disorders (ICRDs) have gained recognition as a severe complication of Parkinson's disease (PD) and are connected to poor quality of life and devastating financial and social problems. This study aimed to evaluate the usefulness of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) and estimate the risk factors for ICRDs in Chinese patients with PD.Methods: 207 PD patients were assessed using the QUIP and evaluated for PD motor and nonmotor symptoms. ICRDs were diagnosed via interviews of patients or their caregivers, and the clinical characteristics of patients with and without ICRDs were compared.Results: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the C-QUIP were 95.0, 83.4, 38.0, 99.4, and 84.5%. The prevalence of each disorder among participants diagnosed via interview was pathological gambling (0.5%), hypersexuality (1.9%), compulsive shopping (1.0%), binge eating (3.9%), hobbyism (1.9%), punding (0.5%), walkabout (0.5%), and dopamine dysregulation syndrome (2.9%). PD patients with ICRDs had longer PD duration, higher Hoehn and Yahr stage, Non-Motor Symptoms Scale (NMSS), and Hamilton-Depression Rating Scale (HAMD). Also, they received a larger total daily levodopa equivalent dose (LED), levodopa dosage, and dopamine agonist only LED (DA-LED) than did PD patients without ICRDs.Conclusions: Given its psychometric properties, the C-QUIP is a valid and rapid screening instrument for assessing of ICRDs in PD patients. Higher Hoehn and Yahr staging, NMSS and HAMD scores, a larger mean LED and levodopa dosage are risk factors for ICRDs.

Relationships between serum 25‐hydroxyvitamin D and homocysteine levels of patients with cognitive impairment in Parkinson’s disease under hypoxia environment

AbstractBackgroundAnalyze relation between serum 25‐hydroxyvitamin D(25‐OH‐VitD), homocysteine(Hcy) , folic acid(FA)and Vitamin B12 levels of patients with cognitive impairment in Parkinson’s disease (PD) on the Qinghai‐Tibet Plateau.MethodFrom July 2017 to December 2020, 200 PD patients (mean age 66.18±12.13years) of Han nationality in PD clinic of Qinghai Provincial People’s Hospital (mean altitude 2,261m) were collected. There were 88 PD with cognitive impairment (PD‐CI) and 112 PD with normal cognitive function (PD‐NC). All patients meet PD diagnostic criteria of British Brain Bank and cognitive diagnostic criteria of International Movement Disorder Association. Serum 25‐OH‐VitD, Hcy, FA and vitamin B12 were determined by chemiluminescence assay.Result1. Prevalence of PD in PDCI group over 70 years old (59.1%) and illiterate group(21.6%)were significantly higher than that in PDNC group (31.3% and 5.4%). 2.Compared with PDNC group, PD duration, ability of daily living(ADL) score, UPDRS total score and serum Hcy significantly increased in PDCI group, serum 25‐OH‐VitD, FA and VitB12 levels significantly decreased in PDCI group. 3.Multivariate logistic regression analysis showed that older age (OR=14.492, P<0.01), low education level(OR=4.631, P<0.05), long course of PD (OR=1.169, P<0.05), ADL disability(OR=1.062, P<0.05), high Hcy, low 25‐OH‐VitD, FA and VitB12 levels(OR=1.065, 0.817, 0.995, 0.927, P<0.05) were independently associated with PDCI group.ConclusionAging, low education level, long, course of PD, ADL disability, hyperhomocysteinemic and VitD deficiency appears to be risk factors for PDCI under hypoxia environment.

The Added Benefit of Opicapone When Used Early in Parkinson's Disease Patients With Levodopa-Induced Motor Fluctuations: A Post-hoc Analysis of BIPARK-I and -II.

Introduction: Opicapone (OPC) was efficacious in reducing OFF-time in two pivotal trials in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (BIPARK-I and -II). Post-hoc analyses of these trials evaluated the efficacy of OPC following pre-defined segmentation of the wide spectrum of motor fluctuations in PD.Methods: Data from matching treatment arms in BIPARK-I and -II were combined for the placebo (PLC) and OPC 50-mg groups, and exploratory post-hoc analyses were performed to investigate the efficacy of OPC 50 mg vs. PLC in subgroups of patients who were in “earlier” vs. “later” stages of both their disease course (e.g., duration of PD <6 years vs. ≥6 years) and levodopa treatment pathway (e.g., number of daily levodopa intakes <4 vs. ≥4). Efficacy variables included changes from baseline in absolute OFF-time and total ON-time.Results: The Full Analysis Set included 517 patients (PLC, n = 255; OPC 50 mg, n = 262). OPC 50 mg was significantly more effective than PLC in reducing OFF-time and increasing ON-time in the majority of subgroup analyses (p < 0.05). Moreover, patients in “earlier” stages of both their disease course and levodopa treatment pathway experienced numerically greater efficacy when using OPC 50 mg, in comparison with those in “later” stages.Conclusion: OPC 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in PD patients. There was also a signal for enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway.

Production and comprehension of co-speech gestures in Parkinson's disease

This study examined how impairments in sensorimotor abilities of individuals with Parkinson's Disease (PD) can be related to the use and understanding of co-speech hand gestures involving literal and figurative actions. We tested individuals with PD (n = 18, 12 males, Mage = 56.5, SDage = 8.16, PD duration since onset: M = 5.36 years, SD = 3.51, Hoehn and Yahr Scale:MH&Y = 2.09, SDH&Y = 0.50) and age- and education-matched neurotypical controls (n = 18, 14 males, Mage = 56.61, SDage = 8.88) with two experimental tasks. In the gesture production task, participants retold the narratives presented to them in a written format. In the gesture comprehension task, participants were asked to match a gesture with a novel verb in literal and figurative sentence contexts. Results showed that patients with PD gestured significantly less than the neurotypical controls. No group differences were found for the type of gesture use. Individuals with PD performed worse than controls on matching gestures with novel verbs, particularly for figurative meanings. Individuals' severity in the disease negatively correlated with their performance for these figurative novel verb-gesture matches. The performances in the two tasks did not correlate. These findings suggest that problems in sensorimotor abilities resulting from PD can influence overall gesture production and gesture comprehension, providing further evidence on the relations between PD and the impaired use of multimodal language.

Off Time Independently Affects Quality of Life in Advanced Parkinson's Disease (APD) Patients but Not in Non-APD Patients: Results from the Self-Reported Japanese Quality-of-Life Survey of Parkinson's Disease (JAQPAD) Study.

Introduction Parkinson's disease (PD) is characterized by a triad of motor symptoms and several nonmotor symptoms (NMS). Identifying the most appropriate treatment is essential for improving patient quality of life (QoL). However, it is still not known which PD symptoms more commonly affect patients with advanced PD (APD) versus non-APD. This study examined the factors that most affected the QoL of patients with APD (defined using the 5-2-1 criteria: ≥5 oral levodopa doses a day, off time ≥2 hours a day, or troublesome dyskinesia ≥1 hour a day) versus non-APD in a large Japanese population using the Japanese Quality-of-Life Survey of Parkinson's Disease (JAQPAD) study. Methods Participants in this self-reported survey-based study included all members of the Japan Parkinson's Disease Association. Questionnaires assessing NMS and QoL (e.g., the 8-item PD Questionnaire [PDQ-8]) were included. Univariate and multivariate regression analyses were conducted to identify clinical factors impacting QoL using the PDQ-8 Summary Index (PDQ-8 SI). Results Of the 3022 eligible patients, 864 were classified as having non-APD and 1599 as having APD. QoL as assessed by the PDQ-8 SI was notably worse in patients with APD versus non-APD (39.2 vs. 26.9, p < 0.0001). Although off time affected QoL only in patients with APD, PD duration and the NMS Questionnaire score significantly contributed to the QoL in both patients with APD and non-APD. Conclusions This study identified the factors more commonly associated with worse QoL in patients with APD versus non-APD. Our findings offer new insights for providing optimal treatment and improving treatment satisfaction in patients with PD.

Short- and Long-Term Effects of DBS on Gait in Parkinson's Disease.

The aim was to compare the short and long-term effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait dysfunction and other cardinal symptoms of Parkinson's disease (PD). Two groups of patients were studied. The first group (short-term DBS, n = 8) included patients recently implanted with STN DBS (mean time since DBS 15.8 months, mean age 58.8 years, PD duration 13 years); the second group (long-term DBS, n = 10) included patients with at least 5 years of DBS therapy (mean time since DBS 67.6 months, mean age 61.7 years, PD duration 17.1 years). Both groups were examined using the Unified Parkinson's Disease Rating Scale (UPDRS) and Gait and Balance scale (GABS) during four stimulation/medication states (ON/OFF; OFF/OFF; OFF/ON; ON/ON). Data were analyzed using repeated measures ANOVA with time since implantation (years) between groups and medication or DBS effect (ON, OFF) within groups. In the short-term DBS group, stimulation improved all UPDRS subscores similar to dopaminergic medications. In particular, average gait improvement was over 40% (p = 0.01), as measured by the UPDRS item 29 and GABS II. In the long-term DBS group, stimulation consistently improved all clinical subscores with the exception of gait and postural instability. In these patients, the effect of levodopa on gait was partially preserved. Short-term improvement of gait abnormalities appears to significantly decline after 5 years of STN DBS in PD patients, while effectiveness for other symptoms remains stable. Progressive non-dopaminergic (non-DBS responsive) mechanisms or deleterious effects of high frequency STN stimulation on gait function may play a role.

A Cross-Sectional Comprehensive Assessment of the Profile and Burden of Non-motor Symptoms in Relation to Motor Phenotype in the Nigeria Parkinson Disease Registry Cohort.

Data on non-motor symptoms (NMS) in black Africans with Parkinson's disease (PD) are sparse. To describe the profile of NMS in the Nigeria PD Registry (NPDR) cohort and explore the relationship between NMS and PD motor phenotype. We conducted a cross-sectional study of the frequency and burden of NMS, based on the non-motor symptoms scale (NMSS) and the Chaudhuri method respectively in our cohort. Baseline demographics, disease characteristics (Hoehn and Yahr stage, MDS-UPDRS total score and Part III motor score), motor phenotype (based on Stebbin et al's algorithm), and levodopa equivalent daily dose (LEDD) were documented. Data are presented for 825 PD whose mean age at study was 63.7 ± 10.1 years, female sex-221 [26.8%] while median PD duration was 36 months. PD phenotypes included tremor-dominant 466 (56.5%), postural instability and gait disorder (PIGD) 259 (31.4%), and indeterminate 100 (12.1%). 82.6% were on treatment (median LEDD of 500 mg/24 hours). 804 (97.5%) endorsed at least 1 NMS. The median NMSS score was 26.0 while subscores for urinary and sexual function domains were significantly higher in males (P< 0.05). PIGD-PD had more frequent NMS and higher frequency of severe/very severe NMSS burden (P= 0.000 for both). Nocturia and fatigue were the most prevalent NMS overall and across motor subtypes. PIGD phenotype and total UPDRS scores were the independent determinants of NMSS scores (P= 0.000). The profile and burden of NMS, and association with motor subtype in our black African cohort is largely similar to descriptions from other populations.

Cross-Sectional Study on the Gut Microbiome of Parkinson's Disease Patients in Central China.

Gastrointestinal dysfunction plays an important role in the occurrence and development of Parkinson’s disease (PD). This study investigates the composition of the gut microbiome using shotgun metagenomic sequencing in PD patients in central China. Fecal samples from 39 PD patients (PD group) and the corresponding 39 healthy spouses of the patients (SP) were collected for shotgun metagenomics sequencing. Results showed a significantly altered microbial composition in the PD patients. Bilophila wadsworthia enrichment was found in the gut microbiome of PD patients, which has not been reported in previous studies. The random forest (RF) model, which identifies differences in microbiomes, reliably discriminated patients with PD from controls; the area under the receiver operating characteristic curve was 0.803. Further analysis of the microbiome and clinical symptoms showed that Klebsiella and Parasutterella were positively correlated with the duration and severity of PD, whereas hydrogen-generating Prevotella was negatively correlated with disease severity. The Cluster of Orthologous Groups of protein database, the KEGG Orthology database, and the carbohydrate-active enzymes of gene-category analysis showed that branched-chain amino acid–related proteins were significantly increased, and GH43 was significantly reduced in the PD group. Functional analysis of the metagenome confirmed differences in microbiome metabolism in the PD group related to short-chain fatty acid precursor metabolism.

Analysis of Impulse Control Disorders (ICDs) and Factors Associated with Their Development in a Parkinson's Disease Population.

Parkinson’s Disease (PD) is a neurodegenerative disease in which non-motor symptoms may appear before motor phenomena, which include Impulse Control Disorders (ICDs). The objective of this study is to identify factors associated with the development of ICDs in PD. An analytical, cross-sectional study was conducted using clinical records from patients diagnosed with PD, both genders, from 40 to 80 years old. Clinical and demographic data were collected: 181 patients were recruited; 80 of them showed PD and ICDs, and they constituted the study group, whereas 101 patients with PD without ICDs constituted the control reference group. The duration of PD was longer in the group with ICDs (p < 0.008), and all patients showed at least one ICD: binge eating (61.29%), compulsive shopping (48.75%), hypersexuality (23.75%), gambling behavior (8.75%), and punding (3.75%). After logistic regression analysis, only the use of dopamine agonists remained associated with ICDs (p < 0.001), and the tremorgenic form was suggested to be a protective factor (p < 0.001). Positive associations were observed between the rigid-akinetic form and compulsive shopping (p < 0.007), between male and hypersexuality (p < 0.018), and between dopamine agonists and compulsive shopping (p < 0.004), and negative associations were observed between motor fluctuations and compulsive shopping (p < 0.031), between Deep Brain Stimulation and binge eating (p < 0.046), and between levodopa consumption and binge eating (p < 0.045). Binge eating, compulsive shopping, and hypersexuality were the most frequent ICDs. Complex forms and motor complications of PD were associated with the development of ICDs.

Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn...

Striatal Subdivisions Estimated via Deep Embedded Clustering With Application to Parkinson's Disease.

Recent fMRI connectivity-based parcellation (CBP) methods have been developed to obtain homogeneous and functionally coherent brain parcels. However, most of these studies utilize traditional clustering methods that neglect hidden nonlinear features. To enhance parcellation performance, here we propose a deep embedded connectivity-based parcellation (DECBP) framework and apply it to determine functional subdivisions of the striatum in public resting state fMRI data sets. This framework integrates fMRI connectivity features into deep embedded clustering (DEC), a deep neural network based on a stacked autoencoder. Compared to three prevalent clustering methods and their combinations with principal component analysis (PCA), the DECBP exhibited a significantly higher similarity between scans, individuals, and groups, indicating enhanced reproducibility. The generated reliable parcellations were also largely consistent with other public atlases. We further explored the functional subunits in the striatum in a data set from 23 Parkinson's disease (PD) subjects and 27 age-matched healthy controls (HC). All putaminal subregions of PD demonstrated lower interhemispheric connectivity than those of HC, which might reflect imbalance in the pathological progression of PD. Such hypo-connectivity was also observed between putaminal subregions and other brain regions, reflecting neuroimaging manifestations of the altered cortico-striato-thalamo-cortical circuit. These observed weaker couplings were associated with PD severity and duration. Our results support the utilization of the DECBP framework and suggest that abnormal connectivity in putaminal subregions may be a potential indicator of PD.

Risk factors of impulsive-compulsive behaviors in PD patients: a meta-analysis.

To summarize the reliable risk factors of impulsive-compulsive behaviors (ICBs) in Parkinson's disease (PD) patients through a meta-analysis on studies in which PD-ICBs were diagnosed by clinical interview. PubMed, Embase, Web of Science, CNKI and Wanfang databases were searched. We selected studies ensuring that diagnosis of ICBs in PD patients depends on semi-structured interviews according to the clinical diagnostic criteria of ICBs. The Newcastle-Ottawa Scale was used to evaluate quality of the included studies. The analyzed factors included demographic information, clinical characteristics of PD and medications. A total of 856 records were screened and 66 full texts were evaluated, and 13 studies (684 PD patients with ICBs [PD-ICBs] and 3,382 PD patients without ICBs [PD-non-ICBs]) were included. Compared with PD-non-ICBs, PD-ICBs were younger in age (-3.7 [-5.53, -1.87], P < 0.0001), with a greater proportion of males (1.64 [1.21, 2.22], P = 0.001), with a younger age of PD onset (-5.42 [-7.87, -2.97], P < 0.0001) and a longer course of PD (1.30 [0.38, 2.22], P = 0.005). PD-ICBs were also associated with higher HAM-D (1.74 [0.47, 3.01], P = 0.007), more levodopa dosage (1.74 [1.09, 2.77], P = 0.02) and dopamine receptor agonists (DA) use (3.96 [2.74, 5.71), P < 0.00001), and higher average dose (levodopa 117.53 [53.59, 181.46], P = 0.0003; DA 80.03 [46.16, 113.90], P < 0.00001), as well as more amantadine use (2.20 [1.42, 3.40], P = 0.0004). The meta-analysis of most factors showed less heterogeneity, except age, age of onset, PD duration, Hoehn and Yahr stage, MMSE and drug dosage. However, whether rapid eye movement sleep behavior disorder, dyskinesia, genetic polymorphism and other factors are risk factors for PD-ICBs remains unclear. This meta-analysis suggests that males, young, early disease onset, long disease duration, depression, dose of levodopa, dopamine receptor agonists and amantadine are risk factors of ICBs in PD patients.

Functional mobility in Parkinson’s disease: associations with motor and non-motor symptoms

Functional mobility (FM) is the ability of people to move in different environments, including at home, at work, and in the community, in order to perform functional activities or tasks, independently and safely. Objective: The aim of the present study was to investigate which motor and/or non-motor symptoms (severity of the motor symptoms, depressive symptoms, and fatigue) have the greatest impact on FM assessed by Modified Parkinson Activity Scale (mPAS) in individuals with Parkinson’s disease (PD). Method: The outcome of interest was FM assessed by mPAS, which includes 14 activities covering three domains (chair transfers, gait akinesia, and bed mobility). Unified Parkinson’s Disease Rating Scale (UPDRS) Part III, Beck Depression Inventory (BDI), and Parkinson’s Disease Fatigue Scale-16 (PFS-16) were used. Results: Forty-four individuals (age: 65±11 years) with PD (PD duration: 7±4 years) were eligible to take part in this cross-sectional, exploratory study. The motor symptoms alone explained 36% (F= 17.85, p&lt;0.001) of the variance in the FM scores. When depressive symptoms were included in the model, the explained variance increased to 45% (F= 12.77, p&lt;0.001). This indicated that individuals who had lower motor and depressive symptoms were less likely to have limitations in FM. Conclusion: The findings of the present study demonstrated that motor symptoms were the best potential predictor of FM in individuals with PD, according to mPAS scores. Additionally, the presence of depressive symptoms should not be overlooked.

Effect of orofacial physiotherapeutic and hygiene interventions on oral health-related quality of life in patients with Parkinson's disease: A randomised controlled trial.

BackgroundParkinson's disease (PD) has a negative effect on oral health and orofacial function, but the subjective experience of orofacial symptoms and their impact on the quality of life is not fully investigated. In addition, knowledge of how to improve the subjective oral symptoms is lacking.ObjectivesTo assess the self‐reported orofacial function and oral health in patients with PD. Furthermore, to investigate the effect of interventions for improvement of oral hygiene and function on oral health–related quality of life (OHRQoL).MethodsA randomised controlled study with delayed intervention was conducted in 29 patients with moderate to advanced PD. Patients were instructed in a standardised exercise programme for the jaw and orofacial muscles and given an individualised oral hygiene programme. The effect on self‐reported orofacial function and OHRQoL was measured after 2 and 4 months using the Nordic Orofacial Test—Screening (NOT‐S), the oral health impact profile (OHIP‐14), self‐reported drooling score and subjective mastication ability.ResultsSelf‐reported oral health and function before the intervention was significantly correlated to the severity and duration of PD. The NOT‐S and drooling score were significantly improved by the interventions after 2 months and the OHIP‐14 after 4 months.ConclusionThe interventions improve the self‐reported orofacial function and OHRQoL. These simple interventions can be implemented in the allied multidisciplinary health care surrounding the PD patient.

Characteristics of Objective Sleep and Its Related Risk Factors Among Parkinson's Disease Patients With and Without Restless Legs Syndrome.

Objective: This study aimed to investigate the objective sleep characteristics and their related risk factors among Parkinson's disease (PD) patients with and without restless legs syndrome (RLS).Methods: A total of 125 patients with PD who underwent overnight polysomnography (PSG) were recruited consecutively. Eighty-one patients, including 27 PD with RLS (PD-RLS) and 54 PD without RLS (PD-NRLS), were included in the final analysis after 1:2 propensity score matching. Demographic, clinical, and polysomnographic data were compared between PD patients with and without RLS. The risk factors for sleep quality were examined using a multiple linear regression model.Results: The prevalence of RLS among PD patients was 28.0% (35/125). The PD-RLS group exhibited a higher score for the Unified Parkinson Disease Rating Scale (UPDRS) III than the PD-NRLS group. Also, the PD-RLS patients displayed significantly shorter total sleep times, worse sleep quality, decreased stage 3 duration, a longer wake time after sleep onset, and a higher arousal index than those without RLS (all p < 0.05). In the multiple linear regression model, PD duration (β = −0.363, 95% CI: −0.652 to −0.074; p = 0.016), UPDRS-III (β = −0.356, 95% CI: −0.641 to −0.071; p = 0.016), and periodic limb movement index (PLMI) (β = −0.472, 95% CI: −0.757 to −0.187; p = 0.002) were determined to be the risk factors influencing sleep quality in PD-RLS patients. The UPDRS-III (β = −0.347, 95% CI: −0.590 to −0.104; p = 0.006) and HAMD scores (β = −0.343, 95% CI: −0.586 to −0.100; p = 0.007) were significantly associated with sleep quality after adjusting for confounding factors in PD-NRLS patients, respectively.Conclusions: PD-RLS patients exhibited more disturbed and fragmented sleep in objective sleep architecture than PD-NRLS patients. The severity of motor symptoms in PD was significantly associated with poor sleep quality in both PD-RLS and PD-NRLS patients. Notably, our findings indicated that periodic limb movements during sleep (PLMS) was the risk factor that influenced the objective sleep quality in PD patients with RLS.

Characterizing Quality of Life in Caregivers of People with Parkinson's Disease and Dysphagia.

Caring for a family member with dysphagia can negatively impact caregiver wellbeing, although little is known about how dysphagia severity or specific symptoms influence this. The purpose of this study was to examine how objective measures of dysphagia in people with Parkinson's disease influenced their caregivers' quality of life. Fifty caregivers (mainly spouses) of people with Parkinson's disease completed a caregiver quality of life survey. Results were compared to medical chart reviews, interviews, and instrumental evaluations of swallowing from the care recipients. Outcomes included caregiver quality of life score, ratings of airway invasion and pharyngeal residue, and Parkinson's disease duration. Descriptive and regression analyses were completed. All caregivers reported reduced quality of life, with 28% having severely disturbed adaptation. Every care recipient with Parkinson's disease demonstrated airway invasion and/or pharyngeal residue. Together, the combination of older care recipient age and longer disease duration was associated with poorer caregiver quality of life [adj. R2 = 0.10-0.12, p = 0.03-0.4]. Neither airway invasion nor pharyngeal residue was related to caregiver quality of life (p > 0.05). Findings confirmed that caregivers of people with Parkinson's disease and dysphagia experience reduced quality of life; however, current methods of assessing caregivers' quality of life may not adequately account for dysphagia-specific burden. Results highlight the urgent need for the development of dysphagia-specific assessments of caregivers' quality of life to facilitate identification of high-risk caregivers and aid the development of support systems to improve health outcomes for caregivers and care recipients.

Association of Dual LRRK2 G2019S and GBA Variations With Parkinson Disease Progression

Despite a hypothesis that harboring a leucine-rich repeat kinase 2(LRRK2) G2019S variation and a glucocerebrosidase (GBA) variant would have a combined deleterious association with disease pathogenesis, milder clinical phenotypes have been reported in dual LRRK2 and GBA variations Parkinson disease (PD) than in GBA variation PD alone. To evaluate the association of LRRK2 G2019S and GBA variants with longitudinal cognitive and motor decline in PD. This longitudinal cohort study of continuous measures in LRRK2 PD, GBA PD, LRRK2/GBA PD, and wild-type idiopathic PD used pooled annual visit data ranging from 2004 to 2019 from the Mount Sinai Beth Israel, Parkinson Disease Biomarker Program, Harvard Biomarkers Study, Ashkenazi Jewish-LRRK2-Consortium, Parkinson Progression Marker Initiative, and SPOT-PD studies. Patients who were screened for GBA and LRRK2 variations and completed either a motor or cognitive assessment were included. Data were analyzed from May to July 2020. The associations of LRRK2 G2019S and GBA genotypes on the rate of decline in Montreal Cognitive Assessment (MoCA) and Movement Disorders Society-Unified Parkinson Disease Rating Scale-Part III scores were examined using linear mixed effects models with PD duration as the time scale. Among 1193 individuals with PD (mean [SD] age, 66.6 [9.9] years; 490 [41.2%] women), 128 (10.7%) had GBA PD, 155 (13.0%) had LRRK2 PD, 21 (1.8%) had LRRK2/GBA PD, and 889 (74.5%) had idiopathic PD. Patients with GBA PD had faster decline in MoCA than those with LRRK2/GBA PD (B [SE], -0.31 [0.09] points/y; P < .001), LRRK2 PD (B [SE], -0.33 [0.09] points/y; P < .001), or idiopathic PD (B [SE], -0.23 [0.08] points/y; P = .005). There was a LRRK2 G2019S × GBA interaction in MoCA decline (B [SE], 0.22 [0.11] points/y; P = .04), but not after excluding severe GBA variations (B [SE], 0.12 [0.11] points/y; P = .28). Patients with GBA PD had significantly worse motor progression compared with those with idiopathic PD (B [SE], 0.49 [0.22] points/y; P = .03) or LRRK2 PD (B [SE], 0.77 [0.26] points/y; P = .004). These findings suggest that longitudinal cognitive decline in patients with GBA PD was more severe than in those with LRRK2/GBA PD, which more closely resembled LRRK2 PD. This further supports the notion of a dominant association of LRRK2 on GBA in individuals who carry both and raises the possibility of an LRRK2 × GBA interaction. However, the biological basis of a dominant association or interaction is not clear and is apparently contrary to basic investigations. Study of a larger cohort of individuals with severe GBA variation is warranted.