| 21. |
|
|
| 22. |
- Lang, Anthony E, et al.
(författare)
-
Integrated Safety of Levodopa-Carbidopa Intestinal Gel From Prospective Clinical Trials.
- 2016
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:4, s. 538-546
-
Tidskriftsartikel (refereegranskat)abstract
- Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.
|
|
| 23. |
- Larsson, Susanna C., et al.
(författare)
-
No clear support for a role for vitamin D in Parkinson's disease : A Mendelian randomization study.
- 2017
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 32:8, s. 1249-1252
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25-hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25-hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation.METHODS: As instrumental variables for the Mendelian randomization analysis, we used 4 single-nucleotide polymorphisms that affect 25-hydroxyvitamin D concentrations (rs2282679 in GC, rs12785878 near DHCR7, rs10741657 near CYP2R1, and rs6013897 near CYP24A1). Summary effect size estimates of the 4 single-nucleotide polymorphisms on PD were obtained from the International Parkinson's Disease Genomics Consortium (including 5333 PD cases and 12,019 controls). The estimates of the 4 single-nucleotide polymorphisms were combined using an inverse-variance weighted meta-analysis.RESULTS: Of the 4 single-nucleotide polymorphisms associated with 25-hydroxyvitamin D concentrations, one (rs6013897 in CYP24A1) was associated with PD (odds ratio per 25-hydroxyvitamin D-decreasing allele, 1.09; 95% confidence interval, 1.02-1.16; P = 0.008), whereas no association was observed with the other 3 single-nucleotide polymorphisms (P > 0.23). The odds ratio of PD per genetically predicted 10% lower 25-hydroxyvitamin D concentration, based on the 4 single-nucleotide polymorphisms, was 0.98 (95% confidence interval, 0.93-1.04; P = 0.56).CONCLUSIONS: This Mendelian randomization study provides no clear support that lowered 25-hydroxyvitamin D concentration is causally associated with risk of PD. © 2017 International Parkinson and Movement Disorder Society.
|
|
| 24. |
- Lerche, Stefanie, et al.
(författare)
-
Cognitive impairment in Glucocerebrosidase (GBA)-associated PD: Not primarily associated with cerebrospinal fluid Abeta and Tau profiles.
- 2017
-
Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 32:12
-
Tidskriftsartikel (refereegranskat)abstract
- A proportion of idiopathic Parkinson's disease patients (PDidiopathic ) with dementia show altered CSF profiles of amyloid β (Aβ) and Tau. PD patients with Glucocerebrosidase (GBA) mutations (PDGBA ) present with even more cognitive decline than seen in PDidiopathic .The objective of this study was to evaluate whether CSF profiles of Aβ and tau are associated with the prominent cognitive impairment in PDGBA .CSF levels of Aβ1-42 , t-Tau, p-Tau, and total alpha-synuclein were assessed in 479 participants (50 PDGBA , 308 PDidiopathic , 121 healthy controls).Older age was associated with cognitive impairment in PDGBA and PDidiopathic . Despite prominent cognitive impairment, PDGBA showed similar CSF levels of Aβ1-42 , t-Tau, and p-Tau as seen in healthy controls. In contrast, lower levels of Aβ1-42 and higher levels of t-Tau and p-Tau were associated with worse cognitive performance in PDidiopathic .The prominent cognitive impairment in PDGBA seems not primarily associated with Aβ and Tau profiles in CSF. © 2017 International Parkinson and Movement Disorder Society.
|
|
| 25. |
|
|
| 26. |
- Marrinan, Sarah L, et al.
(författare)
-
A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.
- 2018
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 33:2, s. 329-332
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD.METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days.RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l-dopa concentration was reduced, indicating more rapid absorption of l-dopa. Camicinal resulted in significant reduction in OFF time (-2.31 hours; 95% confidence interval: -3.71, -0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS-UPDRS score (-12.5; 95% confidence interval: -19.67, -5.29). Camicinal treatment was generally well tolerated.CONCLUSIONS: PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l-dopa. This study provides evidence of an improvement of the motor response to l-dopa in people with PD treated with camicinal 50 mg once-daily compared with placebo, which will require further evaluation.
|
|
| 27. |
- Martinez-Martin, Pablo, et al.
(författare)
-
EuroInf: A Multicenter Comparative Observational Study of Apomorphine and Levodopa Infusion in Parkinson's Disease
- 2015
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 30:4, s. 510-516
-
Tidskriftsartikel (refereegranskat)abstract
- Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI) are two treatment options for patients with advanced Parkinson's disease (PD) and refractory motor complications, with varying cost of treatment. There are no multicenter studies comparing the effects of the two strategies. This open-label, prospective, observational, 6-month, multicenter study compared 43 patients on Apo (48.8% males, age 62.3 +/- 10.6 years; disease duration: 14 +/- 4.4 years; median H & Y stage 3; interquartile range [IQR]: 3-4) and 44 on IJLI (56.8% males, age 62.7 +/- 9.1 years; disease duration: 16.1 +/- 6.7 years; median H & Y stage 4; IQR, 3-4). Cohen's effect sizes (0.8 considered as large) were large with both therapies with respect to total motor, nonmotor, and quality-of-life scores. The Non-Motor Symptoms Scale (NMSS) with Apo showed moderate improvement, whereas sleep/fatigue, gastrointestinal, urinary, and sexual dimensions of the NMSS showed significantly higher improvement with IJLI. Seventy-five percent on IJLI improved in their quality-of-life and nonmotor symptoms (NMS), whereas in the Apo group, a similar proportion improved in quality of life, but 40% in NMS. Adverse effects included peritonitis with IJLI and skin nodules on Apo. Based on this open-label, nonrandomized, comparative study, we report that, in advanced Parkinson's patients, both IJLI and Apo infusion therapy appear to provide a robust improvement in motor symptoms, motor complications, quality-of-life, and some NMS. Controlled, randomized studies are required. (c) 2014 International Parkinson and Movement Disorder Society
|
|
| 28. |
|
|
| 29. |
- Mollenhauer, Brit, et al.
(författare)
-
A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations.
- 2017
-
Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 32:8, s. 1117-1130
-
Forskningsöversikt (refereegranskat)abstract
- Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summarizes perianalytical considerations for biomarker studies (based on immunoassays) in Parkinson's disease, with emphasis on quantifying total α-synuclein protein in biological fluids. Current knowledge and pitfalls are discussed, and selected perianalytical variables are presented systematically, including different temperature of sample collection and types of collection tubes, gradient sampling, the addition of detergent, aliquot volume, the freezing time, and the different thawing methods. We also discuss analytical confounders. We identify gaps in the knowledge and delineate specific areas that require further investigation, such as the need to identify posttranslational modifications of α-synuclein and antibody-independent reference methods for quantification, as well as the analysis of potential confounders, such as comorbidities, medication, and phenotypes of Parkinson's disease in larger cohorts. This review could be used as a guideline for future Parkinson's disease biomarker studies and will require regular updating as more information arises in this growing field, including new technical developments as they become available. In addition to reviewing best practices, we also identify the current technical limitations and gaps in the knowledge that should be addressed to enable accurate and quantitative assessment of α-synuclein levels in the clinical setting. © 2017 International Parkinson and Movement Disorder Society.
|
|
| 30. |
- Mullin, S., et al.
(författare)
-
Evolution and clustering of prodromal parkinsonian features in GBA1 carriers
- 2019
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 34:9, s. 1365-1373
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Five to 25% of patients with PD carry glucocerebrosidase gene mutations, and 10% to 30% of glucocerebrosidase carriers will develop PD by age 80. Stratification of PD risk in glucocerebrosidase carriers provides an opportunity to target disease-modifying therapies. Objective: Cross-sectional and longitudinal survey of prodromal PD signs among glucocerebrosidase carriers. Design: Prospective assessment of 82 glucocerebrosidase mutation carriers and 35 controls over 4 to 5 years for prodromal clinical PD features. Results: At all time points, olfactory (measured using University of Pennsylvania Smell Identification Test) and cognitive (Montreal Cognitive Assessment) function and the International Parkinson and Movement Disorder Society UPDRS parts II and III scores were significantly worse amongst glucocerebrosidase mutation carriers. Progression to microsmia (odds ratio: 8.5; 95% confidence interval: 2.6–28.2; P < 0.05) and mild cognitive impairment (odds ratio: 4.2; 95% confidence interval: 1.1–16.6; P < 0.05) were more rapid compared to controls. Those with worse olfaction also had worse cognition (OR, 1.5; 95% CI: 0.0–2.8; P < 0.05) and depression (OR, 1.3; 95% CI: 0.6–2.8; P < 0.05). No participants reached the MDS prodromal PD diagnostic criteria before PD diagnosis. One participant developed PD. He did not fulfill the International Parkinson and Movement Disorder Society prodromal PD criteria before diagnosis. Conclusion: Assessment of individual and clustered PD prodromal features may serve as a useful tool to identify high-risk subjects for conversion to PD. As a result of the low conversion rate in our glucocerebrosidase mutation carriers to date, prospective validation is needed in larger cohorts to establish the profile of these features in PD convertors. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
|
|
