Journal of Parkinson's disease最新文献

In 2023, a workshop was organized by the UK charity Cure Parkinson's with The Michael J Fox Foundation for Parkinson's Research and Parkinson's UK to review the field of growth factors (GFs) for Parkinson's disease (PD). This was a follow up to a previous meeting held in 2019.¹ This 2023 workshop reviewed new relevant data that has emerged in the intervening 4 years around the development of new GFs and better models for studying them including the merit of combining treatments as well as therapies that can be modulated. We also discussed new insights into GF delivery and trial design that have emerged from the analyses of completed GDNF trials, including the patient voice, as well as the recently completed CDNF trial.² We then concluded with our recommendations on how GF studies in PD should develop going forward.

Background: Urinary tract infections (UTIs) have recently been linked to the onset of multiple synucleinopathies including Parkinson's disease (PD) and multiple system atrophy (MSA). UTIs are more common in people with PD or MSA, than in the general population and within these patient groups the incidence of UTIs is evenly distributed between men and women. UTIs are especially common during disease, but also in the years before clinical diagnosis.

Objective: The mechanisms by which UTIs may contribute to the development and progression of PD or MSA are not well understood. In this work, we evaluate the neuroinflammatory effects of recurrent UTIs on the brain.

Methods: In a humanized mouse model of ɑ-synuclein, we find that repeated administration of uropathogenic E. coli result in sustained UTIs, or a non-resolving chronic UTI phenotype with persistent bacteriuria. Using this model, we investigate the effects of repeated chronic UTIs on neuroinflammation and synucleinopathy in the brain.

Results: Recurrent UTIs lead to behavioral motor changes and are accompanied by persistent neuroinflammatory changes in multiple brain areas. Affected regions with microglial changes involve multiple lower brainstem areas responsible for sickness behavior, including the dorsal vagal complex, and the cingulate cortex.

Conclusions: These results suggests that recurrent UTIs can have lasting impact on the brain, and it warrants further investigation of the potential role of UTIs in the disease progression of synucleinopathies and related neurological disorders.

Background: Best practice guidelines in Parkinson's disease (PD) calls for the immediate initiation of rehabilitation therapies (inclusive of physical (PT) and occupational therapy (OT)) to prevent or ameliorate the loss of function and quality of life associated with disease progression.

Objective: The purpose of this study was to determine the utilization of PT and OT services within the first 2 years following PD diagnosis and to observe longitudinal trends in PT and OT utilization early following PD diagnosis.

Methods: This retrospective cohort study accessed 12 years (2011 to 2023) of data from electronic health records at a midwestern US healthy system. Patients with new PD diagnoses and two-years of visit history were included. The primary outcome was utilization of PT or OT services within two-years of PD diagnosis. Data extracted included demographics and PD therapies. Records of 9720 patients were included in the analyses.

Results: Overall, 36.9% of the cohort (n = 3586) received either physical or occupational therapy within two years of receipt of PD diagnosis. Increasing age, higher comorbidity index, female gender, use of dopamine replacement therapies, and African American race were all positively associated with receipt of PT or OT services (ps < 0.007). The longitudinal trend revealed an average year over year increase in PT/OT utilization of 1.4% between 2013 and 2021 (p < 0.001).

Conclusions: This study shows a promising increase in utilization of PT and OT services over previous reports and longitudinally, however it continues to convey how far clinical practice continues to lag behind best practice and scientific recommendation.

Background: Compensatory mechanisms in Parkinson's disease (PD) are thought to explain the temporal delay between the beginning of the neurodegenerative process and the appearance of clinical signs. The enhanced structural integrity of the corticospinal tract was previously suggested as one of these mechanisms.

Objective: To understand the relations between corticospinal tract integrity and the anatomical, clinical, electrophysiological, and genetic PD characteristics.

Methods: We analyzed diffusion tensor imaging (DTI) fractional anisotropy (FA) data from 40 genotyped patients with PD (18 without known genetic cause, 11 with LRRK2-PD and 11 with GBA-PD) who were candidates for subthalamic deep brain stimulation (STN-DBS) and from 25 healthy, age-matched, controls.

Results: PD is associated with higher corticospinal FA values (p < 0.001) that are negatively correlated with the disease duration (p = 0.032), confirming previous results. Higher FA values are negatively correlated with cerebral grey matter volumes (p < 0.001) but not with the motor or cognitive PD characteristics, or with the subthalamic beta-oscillatory activity measured intra-operatively. Increased corticospinal FA values are strongly affected by the genetic etiology of PD, with higher values in the monogenic forms of the disease (p < 0.001). The compensatory index, calculated by dividing the corticostriatal FA value by the cerebral grey matter volume, is highest in GBA-PD (p < 0.001) at the time of evaluation for STN-DBS.

Conclusions: The genetic etiology of PD strongly shapes corticospinal tract changes along with disease-duration and cerebral grey matter atrophy. The changes may serve as compensatory mechanism.

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with diverse clinical phenotypes, prompting the development of new diagnostic criteria known as the MDS-PSP classification. However, little is known about the prognostic value of this classification in order to better stratify patients for the clinical trials.

Objective: To assess the impact of the different clinical phenotypes according to the MDS-PSP classification on prognosis using the clinical milestones of death, severe dysphagia, institutionalization, and need for walking aid.

Methods: A prospective cohort of 205 PSP patients from Lille University Hospital was analyzed retrospectively. Patients were classified into different MSD-PSP phenotypes according to their clinical presentation after 3 years of follow-up. The milestones of death, severe dysphagia, institutionalization, and need for walking aid were recorded, and a survival analysis was performed to describe the prognosis of each disease presentation.

Results: Median survival time was 6.4 (interquartile range (IQR): 4.8-8.6) years and mean diagnostic delay from symptom onset was 38.1 ± 22.5 months. PSP Richardson Syndrome (PSP-RS) had a poorer survival rate and a higher occurrence of severe dysphagia and need for walking aid compared to PSP variants such as PSP Parkinsonism (PSP-P), PSP postural instability without ocular motor dysfunction (PSP-PI), and other rare phenotypes.

Conclusions: PSP-RS has a less favorable prognosis compared to PSP variants stratified according to the MDS-PSP classification. This classification could assist in selecting patients for clinical trials and help design outcomes that account for the disease heterogeneity.

Background: Depression often co-occurs with Parkinson's disease (PD) and is effectively treated with selective serotonin reuptake inhibitors (SSRI) and serotonin and noradrenaline reuptake inhibitors (SNRI), but their effect on motor symptoms has not yet been conclusively demonstrated. Objective: To assess the impact of the SSRI/SNRI on the motor symptoms of PD. Methods: We used data from the Parkinson's Progression Markers Initiative database, in a matched subject design with a target group (N = 47) which had been taking SSRI/SNRI medication and a control group (N = 90) which had not. Matching criteria included Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) total score and its subscales' scores, and levodopa equivalent daily dose (LEDD) at the time of the first examination (initial LEDD). For the target group, we compared the MDS-UPDRS-III score before and after taking the SSRI/SNRI medication, while for the control group we compared two equally spaced examinations. Results: In the target group, we found a greater worsening of motor scores, which was associated with lower values of initial LEDD. In addition, apathy was an independent predictor of motor worsening. Conclusions: SSRI/SNRI-use seems to be characterized by a steeper worsening of motor symptoms, which can be predicted by a lower initial LEDD. Further research should continue to investigate the effect of SSRI/SNRI-use on motor symptoms in PD.

Background: Recent evidence suggests a link between glycoprotein non-metastatic melanoma protein B (GPNMB) and Parkinson's disease (PD) pathogenesis. Although elevated plasma GPNMB levels associated with disease severity have been reported in PD, cerebrospinal fluid (CSF) alterations remain elusive.

Objective: To explore CSF GPNMB alterations and its clinical significance in PD.

Methods: This study enrolled 118 sporadic PD patients and 40 controls. We examined the potential associations between CSF GPNMB levels and the clinical characteristics or biomarkers of neurodegenerative pathogenesis.

Results: PD patients had higher CSF GPNMB levels than controls (p = 0.0159). In the PD group, CSF GPNMB levels correlated with age (age at examination: r_s= 0.2511, p = 0.0061; age at onset: r_s= 0.2800, p = 0.0021) and the severity of motor and cognitive dysfunction (MDS-UPDRS III score: r_s= 0.1998, p = 0.0347; Mini-Mental State Examination score: r_s= -0.1922, p = 0.0370). After correcting for multiple comparisons, the correlation with age at onset remained significant. CSF GPNMB levels were also positively correlated with CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in both the PD (r_s= 0.3582, p < 0.0001) and control (r_s= 0.4743, p = 0.0023) groups. Furthermore, multiple regression analysis revealed CSF sTREM2 level as the strongest determinant of CSF GPNMB levels in the PD group (t-value = 3.49, p = 0.0007).

Conclusions: Elevated CSF GPNMB levels, linked with age and microglial activation, may be a valuable marker for understanding the interplay between aging, neuroinflammation, and PD pathology.

Festination is an episodic gait disorder which is often a precursor of freezing of gait episodes in Parkinson's disease patients. We discuss what lessons can be learned from a patient who had to quit playing tennis as he repeatedly fell due to backward festination-like steps.

Background: Expiratory muscle strength training (EMST) is acknowledged for its therapeutic benefits in Parkinson's disease (PD), yet long-term adherence remains a challenge.

Objective: The primary aim of this study was to assess the preliminary effects of EMST coupled with a mobile health app (SpiroGym) on self-efficacy and exercise adherence in PD patients. The secondary aim was to assess the usability of the SpiroGym app.

Methods: This single-group, multicenter, multinational proof-of-concept study involved 63 PD patients across four tertiary PD centers. Participants were enrolled in either a 1-week (n = 35) or 24-week (n = 28) EMST program coupled with SpiroGym app. Self-efficacy was assessed using the Self-Efficacy for Home Exercise Program scale (SEHEPS) and exercise adherence was monitored by SpiroGym app. Usability was evaluated using the System Usability Scale.

Results: Post-intervention, significant improvements in SEHEPS were observed in 1-week group (d = 0.48; p = 0.02) and 24-week group (d = 0.57; p = 0.002). Adherence rates in the 24-week PD patient group were high throughout the course of the study. Post-training SEHEPS was found to correlate (rho = 0.55; adjusted p = 0.016) with adherence to EMST during the non-supervised maintenance phase. The SpiroGym app exhibited high usability (>85th percentile score), with no significant differences noted between short-term and long-term use, indicating sustained user satisfaction.

Conclusions: The results of our study suggest a promising role for SpiroGym app in supporting adherence to home-based EMST in PD patients. Nevertheless, future comparative studies are required to confirm SpiroGym's effectiveness.