Parkinson's Disease最新文献

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. However, the currently available treatments could only relieve symptoms. Novel therapeutic targets are urgently needed. Several previous studies mentioned that protein tyrosine phosphatase 1B (PTP1B) acted as a negative regulator of the insulin signal pathway and played a significant role in the inflammation process. However, few studies have investigated the role of PTP1B in the central nervous system. Our study showed that suramin, an inhibitor of PTP1B, could improve neuronal damage. It could significantly attenuate the interferon-gamma-induced upregulation of proinflammatory cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). It enhanced M2 type microglia markers, such as arginase-1 and Ym-1 in BV2 murine microglial cells. PTP1B inhibition also reversed 6-hydroxydopamine- (6-OHDA-) induced downregulation of phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells. Besides, we knocked down and overexpressed PTP1B in the SH-SY5Y cells to confirm its role in neuroprotection. We also verified the effect of suramin in the zebrafish PD model. Treatment with suramin could significantly reverse 6-OHDA-induced locomotor deficits and improved tyrosine hydroxylase (TH) via attenuating endoplasmic reticulum (ER) stress biomarkers. These results support that PTP1B could potentially regulate PD via antineuroinflammation and antiapoptotic pathways.

Parkinson's disease (PD) is a common neurodegenerative disease in the middle-aged and the elderly. Symptoms of autonomic dysfunctions are frequently seen in PD patients, severely affecting the quality of life. This review summarizes the epidemiology, clinical manifestations, and treatment options of autonomic dysfunctions. The clinical significance of autonomic dysfunctions in PD early diagnosis and differential diagnosis is also discussed.

Background: Self-management strategies are important in healthcare for people with Parkinson's to improve daily living. There is limited evidence on effectiveness in Parkinson's, and the active components of effective self-management strategies are uncertain. This review aims to identify and synthesise the qualitative evidence regarding the experiences of self-management components by people with Parkinson's and their carers.

Methods: MEDLINE, PsycINFO, Embase, Web of Science, and CINAHL were searched from inception to July 8, 2020, for qualitative research concerning self-management for people with Parkinson's. Data were coded and thematically synthesised using NVivo. Findings. Of 9547 search results, six papers were included in the final thematic synthesis. The studies reviewed consisted of 147 participants: 104 were people with Parkinson's and 43 were carers. Seven main themes were derived concerning self-management of people with Parkinson's: (1) medication management, (2) physical exercise, (3) self-monitoring techniques, (4) psychological strategies, (5) maintaining independence, (6) encouraging social engagement, and (7) providing knowledge and information. These components should be incorporated as relevant strategies and techniques and should be specific as well as tailored to different stages of the disease. Discussion. Self-management programmes for people with Parkinson's should include the seven themes presented as part of this review and pay particular attention to presenting relevant information and skills as they relate to different stages of the disease. Tailoring information and social engagement were two components that required specific attention in order to engage people with Parkinson's effectively.

Background: Deep brain stimulation (DBS) for Parkinson's disease (PD) has evolved as a well-established treatment in neurosurgery, and identifying appropriate surgical candidates could contribute to better DBS outcomes. The Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD) is a reasonable screening tool for assessing DBS candidacy in PD patients; however, a Chinese version of FLASQ-PD is needed for functional neurosurgery units in China. In this study, we translated the FLASQ-PD to Chinese and assessed its reliability and validity for Chinese PD patients.

Methods: The FLASQ-PD was translated before the study formally started. A single-center retrospective analysis of FLASQ-PD was performed at the Ruijin Hospital, affiliated with Shanghai Jiaotong University School of Medicine, between July and December 2019. The Unified Parkinson Disease Rating Scale III (UPDRS-III) was also used to assess PD patients on and off medication. All patients were evaluated for surgical candidacy by specialists.

Results: Overall, 115 PD patients, 25 with parkinsonism and six with multiple system atrophy were consecutively included. Internal consistency of the Chinese FLASQ-PD was roughly adequate (Cronbach's alpha = 0.664). There were significant differences in mean total scores of the Chinese FLASQ-PD between the diagnostic (Kruskal-Wallis H value = 37.450, p ≤ 0.001) and surgery-candidacy groups (H = 48.352, p ≤ 0.001). Drug improvements in UPDRS-III scores were mildly correlated with the Chinese FLASQ-PD scores in the surgery-ready group (Pearson correlation = 0.399, p=0.001).

Conclusions: The Chinese FLASQ-PD, which is a simple and efficient screening tool for clinicians, was developed and initially validated in this retrospective single-center study.

Background: Meta-analyses have demonstrated cognitive training (CT) benefits in Parkinson's disease (PD) patients. However, the patients' cognitive status has only rarely been based on established criteria. Also, prediction analyses of CT success have only sparsely been conducted.

Objective: To determine CT effects in PD patients with mild cognitive impairment (PD-MCI) on cognitive and noncognitive outcomes compared to an active control group (CG) and to analyze CT success predictors.

Methods: Sixty-four PD-MCI patients (age: 67.61 ± 7.70; UPDRS-III: 26.58 ± 13.54; MoCA: 24.47 ± 2.78) were randomized to either a CT group or a low-intensity physical activity CG for six weeks (twice weekly, 90 minutes). Outcomes were assessed before and after training. MANOVAs with follow-up ANOVAs and multiple regression analyses were computed.

Results: Both interventions were highly feasible (participation, motivation, and evaluation); the overall dropout rate was 4.7%. Time × group interaction effects favoring CT were observed for phonemic fluency as a specific executive test (p=0.018, η _p ²=0.092) and a statistical trend for overall executive functions (p=0.095, η _p ²=0.132). A statistical trend for a time × group interaction effect favoring CG was shown for the digit span backward as a working memory test (p=0.098, η _p ²=0.043). Regression analyses revealed cognitive baseline levels, education, levodopa equivalent daily dose, motor scores, and ApoE status as significant predictors for CT success.

Conclusions: CT is a safe and feasible therapy option in PD-MCI, yielding executive functions improvement. Data indicate that vulnerable individuals may show the largest cognitive gains. Longitudinal studies are required to determine whether CT may also attenuate cognitive decline in the long term. This trial is registered with DRKS00010186.

The aim of the present study was to determine the relation between urinary dysfunction and nigrostriatal dopaminergic degeneration in early and untreated Parkinson's disease (PD). The data were obtained from Parkinson's Progression Markers Initiative database. Two hundred and seventy-five patients and 149 healthy controls were included in our analysis. Urinary symptoms were evaluated with the Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT). We performed correlation analyses between ¹²³I-FP-CIT SPECT imaging data and severity of urinary symptoms in patients with PD and healthy controls. Early and untreated patients with PD exhibited worse urinary symptoms when compared with healthy controls. The severity of urinary symptoms significantly correlated with dopamine transporter binding levels in the caudate and the putamen. After controlling for age and sex, the severity of storage symptoms significantly correlated with dopamine transporter binding levels in the less affected side of the putamen (r = -0.172, p=0.004). The correlation was observed in both male (r = -0.152, p=0.043) and female patients (r = -0.217, p=0.034). No correlations were found between dopamine transporter binding levels and voiding symptoms in male or female patients, or any urinary symptoms in healthy controls. Worse storage symptoms reflect greater nigrostriatal dopaminergic loss in early and untreated PD.

Methods: We assessed the attitude of two groups of psychiatrists (practicing in Italy and Thailand) towards the prescription of anticholinergics by a short online survey consisting of four questions. A total of one hundred questionnaires were sent out (50 in Italy and 50 in Thailand), and 42 psychiatrists responded to the survey.

Results: When comparing the two cohorts, the difference, both for age and years of practice, was statistically significant (p < 0.00001 and p < 0.0001, respectively), with Thai psychiatrists being younger and with less time in practice as specialists. The results from the survey showed that the prescription of anticholinergic drugs at the beginning of the antipsychotic treatment was used by 5 psychiatrists (20.0%) of the Italian cohort and by 1 (5.9%) of the Thai cohort. Regarding the Italian psychiatrists who did not prescribe anticholinergics concomitantly with neuroleptics, we found that 5 (25.0%) of them had prescribed anticholinergics in the past but had abandoned this practice, while 15 (93.7%) of the Thai psychiatrists who did not prescribe anticholinergics at the moment of the survey answered that they had prescribed these drugs in the past.

Conclusion: According to this preliminary survey, the practice to use anticholinergics as a treatment for tardive syndromes is still relatively common, particularly in psychiatrists of the older generation, but seemingly in decline over the years.

Olfactory dysfunction (OD) is a prominent nonmotor symptom in Parkinson's disease (PD), and OD is a supportive diagnostic criterion for PD. Physicians often ask their patients if they have noticed a smell disorder. This study evaluates the diagnostic validity of OD self-assessment in PD. To this end, 64 PD patients and 33 age-matched healthy controls were enrolled in a study assessing subjective and objective olfactory functioning. To examine subjective olfactory abilities, first, patients and controls had to classify their olfactory sense as "impaired" or "unimpaired," comparable to a realistic situation in an outpatient setting. Second, to evaluate subjective olfactory acuity, a visual analogue scale (VAS) was used. Third, the Sniffin' Sticks test battery was used as an objective instrument to diagnose OD. Categorical olfactory self-assessment predicts the classification normosmic versus hyposmic based on the global Sniffin' Sticks score (TDI) with a sensitivity of 0.79 and a specificity of 0.45. TDI correlated significantly with the VAS (r = 0.297, p = 0.017). The ROC curve analysis, using the VAS rating as a predictor for objective olfaction, revealed 42 as the best possible cutoff score with an area under the curve of 0.63. These results demonstrate that olfactory self-assessments show a low accuracy and are not suitable for the diagnosis of a smell disorder in PD. Objective measures are necessary to evaluate olfactory sense in clinical and research settings.

Background: Patients with advanced stage Parkinson's disease (PD) typically present with a myriad of motor and nonmotor symptoms in addition to comorbidities and, as a consequence, polypharmacy.

Objective: To analyze a series of cases of advanced PD in which a clinical or surgical emergency played a trigger role in the irreversible progression of landmarks of the course of the disease.

Methods: Data were collected during a 13-month observational period of a cohort of 230 PD patients, in 751 medical appointments. We included a total of 13 (5.65% of the total number) patients with advanced PD defined by Hoehn & Yahr (H&Y) stage ≥3 who presented with various clinical and surgical complications which, with the contribution of drug interventions, led to significant worsening of patients' overall clinical condition.

Results: Hip fractures and infections were the most common complications identified. As part of this scenario, most patients presented with delirium, often requiring treatment with dopamine receptor blocking agents and/or had dopaminergic treatment withdrawn. Upon reassessment after 3 months, all patients remained bed or wheel chair bound (H&Y 5) and presented significant worsening of their UPDRS part III score of at least 10 points (mean 51.5 ± 3.3; paired t-test two-tailed p < 0.0001 compared to baseline). The mean dose of levodopa at baseline was 907.7 ± 149.8 mg (600-1200) and significantly higher (paired t-test two-tailed p < 0.0001) on follow-up, 1061.5 ± 175.8 mg (700-1300).

Conclusion: Clinical and surgical emergencies are major determinants for a progression of PD to more advanced stages.

We conducted an observational study to investigate clinical predictors of cognitive decline in patients with mild cognitive impairment (MCI), with a focus on patients with Parkinson's disease (PD) and Alzheimer's disease (AD). The study was performed with detailed neuropsychological testing, a portable device for gait analysis, and a comprehensive geriatric assessment for patients with MCI. Cognitive decline was defined as subjective cognitive impairment with an objective decline in the Mini-Mental State Examination (MMSE) ≥2 points at the one-year follow-up. Participants (n = 74) had a median age of 70 (interquartile range 60-79) years, and 45.9% of them were women. At the end of the study, 17.6% of the patients with MCI had a cognitive decline. Although no differences were observed between groups at the baseline cognitive study, patients with PD-MCI demonstrated more cognitive decline than patients with AD-MCI (28.6% vs. 7.7% p = 0.03). Patients with PD-MCI had more physical disabilities, including scores of instrumental activities of daily living (IADL), Tinetti balance, and gait scores, and some Timed Up and Go components. Initial Clinical Dementia Rating-Sum of Boxes score was a better predictor of future cognitive decline than MMSE in PD-MCI. For predicting the occurrence of cognitive decline in PD-MCI, the prediction accuracy increased from the reduced model (AUC = 0.822, p < 0.001) to the full model (a total of five independent variables, AUC = 0.974, p < 0.001). Given the potentially modifiable predictor, our findings also highlight the importance of identifying sleep quality and the ability to perform IADL.