Journal of Parkinson's disease最新文献

Background: Physical exercise interventions are known to improve quality of life, motor and non-motor symptoms in people with Parkinson's disease (PD). However, systematic reviews and meta-analyses on cognitive outcomes are rare.

Objective: To perform a systematic review and meta-analysis of physical exercise intervention effects compared with passive and active control groups (CGs) on global cognition in people with PD.

Methods: A literature search was performed for randomized controlled trials (RCTs) on physical exercise interventions in PD using nine databases. We included RCTs reporting global cognition outcomes. A meta-analysis was performed using random-effects models and standardized mean differences (SMDs) with 95% confidence intervals (CIs). Bias was assessed with the revised Cochrane Risk of Bias tool and the certainty of evidence was rated using the GRADE approach.

Results: Seventeen studies (ten with passive, seven with active CGs) were included in the systematic review. Exercise interventions varied considerably between studies. The meta-analysis included nine studies with 236 people with PD (seven with passive, two with active CGs). The SMD was 0.33 (95% CI 0.00; 0.65) demonstrating a small effect (p = 0.05) in favor of physical exercise. Compared with passive CGs, physical exercise had a small non-significant effect (SMD = 0.22, 95% CI -0.14;0.58, p = 0.24). Compared with active CGs, physical exercise had a medium significant effect (SMD = 0.72, 95% CI 0.12;1.33, p = 0.02).

Conclusions: Physical exercise may increase global cognition in people with PD, but the evidence is very uncertain. Further large-scale RCTs are needed to confirm this finding and to identify the most effective type of physical exercise for improving cognition.

Parkinson's disease (PD) is a chronic and complex neurodegenerative disorder. Conventional pharmacological or surgical therapies alone are often insufficient at adequately alleviating disability. Moreover, there is an increasing shift toward person-centered care, emphasizing the concept of "living well". In this context, arts-based interventions offer great promise, functioning as platforms for creative expression that could provide novel mechanisms to promote quality of life. Here we present a qualitative review of arts-based interventions for PD, including music, dance, drama, visual arts, and creative writing. For each, we discuss their applications to PD, proposed mechanisms, evidence from prior studies, and upcoming research. We also provide examples of community-based projects. Studies to date have had relatively small sample sizes, but their findings suggest that arts-based interventions have the potential to reduce motor and non-motor symptoms. They may also empower people with PD and thereby address issues of self-esteem, foster personal problem-solving, and augment holistic well-being. However, there is a paucity of research determining optimal dosage and symptom-specific benefits of these therapies. If art were a drug, we would have to perform appropriately powered studies to provide these data before incorporating it into routine patient care. We therefore call for further research with properly designed studies to offer more rigorous and evidence-based support for what we intuitively think is a highly promising approach to support individuals living with PD. Given the possible positive impact on people's lives, arts-based approaches merit further development and, if proven to be effective, systematic inclusion within integrated management plans.

Symptoms of autonomic dysfunction are prevalent and can be very debilitating, reducing the quality of life in patients with Parkinson's disease (PD) and other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Non-pharmacological therapies are key to effective management and are frequently used alone in patients with mild autonomic symptoms, or in combination with pharmacological therapies in patients with moderate and severe symptoms. This article focuses on non-pharmacological approaches. Our objective was to review the non-drug and non-surgical approaches to treating autonomic symptoms in patients with PD and other synucleinopathies, focusing on cardiovascular, gastrointestinal, and genitourinary autonomic dysfunction. Evidence supporting the effectiveness of non-pharmacological treatment for the management of neurogenic orthostatic hypotension, supine hypertension, constipation, and bladder and sexual dysfunction is available. High-quality prospective trials are scarce, yet some non-pharmacological interventions (e.g., physical counter maneuvers) can be evaluated relatively quickly on an individual basis and often seem effective. The emerging variety of clinical presentations advocates for a stepwise, individualized, and non-pharmacological approach for the management of autonomic symptoms. Often, the first step is to reduce or discontinue drugs that cause or aggravate autonomic symptoms followed by lifestyle measures. While non-pharmacological and non-surgical treatments are available and, in many cases, effective to improve symptoms of autonomic dysfunction in PD and other synucleinopathies, they are often overlooked. Large randomized trials testing and comparing non-pharmacological approaches are warranted.

Background: Increased prevalence of cardiovascular autonomic failure might play a key role on Parkinson's disease (PD) progression of glucocerebrosidase gene (GBA)-mutated patients, determining a malignant phenotype of disease in these patients.

Objective: To objectively characterize, for the first time, the cardiovascular autonomic profile of GBA-mutated patients compared to idiopathic PD patients by means of cardiovascular reflex tests (CRTs).

Methods: This is a case-control (1 : 2) study on PD patients belonging to well-characterized prospective cohorts. For each PD patient carrying GBA variants, two idiopathic PD patients, matched for sex and disease duration at CRTs, were selected. Patients recruited in these cohorts underwent a complete clinical and instrumental evaluation including specific autonomic questionnaires, CRTs and extensive genetic analysis.

Results: A total of 23 GBA-PD patients (19 males, disease duration 7.7 years) were included and matched with 46 non-mutated PD controls. GBA-mutated patients were younger than controls (59.9±8.1 vs. 64.3±7.2 years, p = 0.0257) and showed a more severe phenotype. Despite GBA-mutated patients reported more frequently symptoms suggestive of orthostatic hypotension (OH) than non-mutated patients (39.1% vs 6.5%, p = 0.001), the degree of cardiovascular autonomic dysfunction, when instrumentally assessed, did not differ between the two groups, showing the same prevalence of neurogenic OH, delayed OH and cardiovascular reflex impairment (pathological Valsalva maneuver).

Conclusion: GBA-PD patients did not show different instrumental cardiovascular autonomic pattern than non-mutated PD. Our findings suggested that symptoms suggestive of OH should be promptly investigated by clinicians to confirm their nature and improve patient care and management.

During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The most important among them are REM sleep behavior disorder (RBD) and olfactory dysfunction. RBD is a parasomnia characterized by the loss of REM sleep muscle atonia and dream-enacting behaviors. Olfactory dysfunction in individuals with prodromal PD is usually described as hyposmia (reduced sense of smell) or anosmia (complete loss of olfactory function). These symptoms can precede the full expression of motor symptoms by decades. A close comprehension of these symptoms and the underlying mechanisms may enable early screening as well as interventions to improve patients' quality of life. Therefore, these symptoms have unmatched potential for identifying PD patients in prodromal stages, not only allowing early diagnosis but potentially opening a window for early, possibly disease-modifying intervention. However, they come with certain challenges. This review addresses some of the key opportunities and pitfalls of both RBD and olfactory dysfunction as early markers of PD.

Background: Sexual health (SH) is influenced by several biological, mental, and social factors that may be negatively impacted by Parkinson's disease (PD). Despite its prevalence and relevance for quality of life, the factors that affect SH in men with PD (MwPD) are still poorly understood.

Objectives: To investigate the impact of motor, non-motor, and social aspects on the SH in MwPD.

Methods: We conducted a cross-sectional study of 80 men (mean-age 53.55±10.8) in stages 1-3 of Hoehn and Yahr classification (H&Y), who reported having an active sex life in the last six months. The following data were collected for each person: 1) Demographic and clinical features; 2) global cognitive capacity (T-MoCA); 3) Non-Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part I); 4) Motor Aspects of Experiences of Daily Living (MDS-UPDRS, part II); 5) Fatigue (FSS); 6) Self-esteem (RSES); 7) Sleep disorder (PDSS); 8) Couple relationship quality (DAS); 9) Depressive signals (BDI); 10) Short-term sexual health by International Index of Erectile Function (IIFE); and 11) Long-term sexual health by Sexual Quotient-Male (SQ-M).

Results: Our results showed that although several motor, non-motor, and social factors were correlated with SH, only motor disability levels in daily living predicted short-term SH and erectile dysfunction, while only depression predicted long-term SH in MwPD. Age, disease onset, and medication daily dosage were not correlated with SH.

Conclusions: Our findings confirm that multidimensional factors can affect the SH of MwPD and emphasize that only a multi-professional team can offer proper care to improve SH in MwPD.

Background: The detailed trajectory of data-driven subtypes in Parkinson's disease (PD) within Asian cohorts remains undisclosed.

Objective: To evaluate the motor, non-motor symptom (NMS) progression among the data-driven PD clusters.

Methods: In this 5-year longitudinal study, NMS scale (NMSS), Hospital Anxiety Depression Scale (HADS), and Epworth sleepiness scale (ESS) were carried out annually to monitor NMS progression. H& Y staging scale, MDS-UPDRS part III motor score, and postural instability gait difficulty (PIGD) score were assessed annually to evaluate disease severity and motor progression. Five cognitive standardized scores were used to assess detailed cognitive progression. Linear mixed model was performed to assess the annual progression rates of the longitudinal outcomes.

Results: Two hundred and six early PD patients, consisting of 43 patients in cluster A, 98 patients in cluster B and 65 subjects in cluster C. Cluster A (severe subtype) had significantly faster progression slope in NMSS Domain 3 (mood/apathy) score (p = 0.01), NMSS Domain 4 (perceptual problems) score (p = 0.02), NMSS Domain 7 (urinary) score (p = 0.03), and ESS Total Score (p = 0.04) than the other two clusters. Cluster A also progressed significantly in PIGD score (p = 0.04). For cognitive outcomes, cluster A deteriorated significantly in visuospatial domain (p = 0.002), while cluster C (mild subtype) deteriorated significantly in executive domain (p = 0.04).

Conclusions: The severe cluster had significantly faster progression, particularly in mood and perceptual NMS domains, visuospatial cognitive performances, and postural instability gait scores. Our findings will be helpful for clinicians to stratify and pre-emptively manage PD patients by developing intervention strategies to counter the progression of these domains.

Reduced spontaneous blinking is a recognized Parkinson's disease (PD) feature. In contrast, voluntary blinking has been less studied and might serve as a measurable marker of facial bradykinesia. We tested 31 PD patients and 31 controls. Participants were filmed during conversation and a rapid blinking task. Both tasks were videorecorded to count the number of blinks per second. PD patients had lower blink rates. Rapid blinking accurately discriminated between groups with 77% sensitivity and 71% specificity. To conclude, rapid blinking may be a simple and quantifiable task of facial bradykinesia.

Targeted delivery of α-synuclein using AAV vectors has over the two decades since its introduction developed into a versatile tool for modeling different aspects of synucleinopathy, mimicking those seen in Parkinson's disease and related Lewy body disorders. The viral vector approach to disease modeling is attractive in that the expression of α-synuclein, wild-type or mutated, can be confined to defined anatomical structures and targeted to selected cell populations using either cell-type specific promoter constructs or different natural or engineered AAV serotypes. AAV-α-synuclein was initially used to model progressive α-synuclein pathology in nigral dopamine neurons, and, like the standard 6-OHDA model, it has most commonly been applied unilaterally, using the non-injected side as a reference and control. In recent years, however, the AAV-α-synuclein model has become more widely used to induce Parkinson-like synuclein pathology in other relevant neuronal systems, such as the brainstem noradrenergic and serotonergic neurons, the vagal motor neurons, as well as in oligodendrocytes, the prime target relevant to the pathology seen in multiple system atrophy. The purpose of this review is to give an overview of the progress made in the use of the AAV-α-synuclein model over the last two decades and summarize the state-of-the art in the use of the AAV-α-synuclein model for disease modeling in rats and mice.