| 1. |
- Albrecht, Franziska, et al.
(author)
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Effects of a Highly Challenging Balance Training Program on Motor Function and Brain Structure in Parkinson's Disease
- 2021
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:4, s. 2057-2071
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Journal article (peer-reviewed)abstract
- Background: Parkinson's disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms. Objective: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure. Methods: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed. Results: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training. Conclusion: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects.
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| 2. |
- Bacelis, J., et al.
(author)
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Decreased Risk of Parkinson's Disease after Rheumatoid Arthritis Diagnosis: A Nested Case-Control Study with Matched Cases and Controls
- 2021
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In: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 11:2, s. 821-832
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Journal article (peer-reviewed)abstract
- Background: Rheumatoid arthritis (RA) and the genetic risk landscape of autoimmune disorders and Parkinson's disease (PD) overlap. Additionally, anti-inflammatory medications used to treat RA might influence PD risk. Objective: To use a population-based approach to determine if there is an association between pre-occurring rheumatoid arthritis (RA) and later-life risk of PD. Methods: The study population was 3.6 million residents of Sweden, who were alive during part or all of the follow-up period; 1997-2016. We obtained diagnoses from the national patient registry and identified 30,032 PD patients, 8,256 of whom each was matched to ten controls based on birth year, sex, birth location, and time of follow-up. We determined the risk reduction for PD in individuals previously diagnosed with RA. We also determined if the time (in relation to the index year) of the RA diagnosis influenced PD risk and repeated the analysis in a sex-stratified setting. Results: Individuals with a previous diagnosis of RA had a decreased risk of later developing PD by 30-50% compared to individuals without an RA diagnosis. This relationship was strongest in our conservative analysis, where the first PD diagnosis occurred close to the earliest PD symptoms (odds ratio 0.47 (CI 95% 0.28-0.75, p=0.0006); with the greatest risk reduction in females (odds ratio 0.40 (CI 95% 0,19-0.76, p=0.002). Discussion: Our findings provide evidence that individuals diagnosed with RA have a significantly lower risk of developing PD than the general population. Our data should be considered when developing or repurposing therapies aimed at modifying the course of PD. © 2021 - The authors. Published by IOS Press.
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| 3. |
- Björklund, Tomas, et al.
(author)
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Next-Generation Gene Therapy for Parkinson's Disease Using Engineered Viral Vectors
- 2021
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:s2, s. 209-217
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Research review (peer-reviewed)abstract
- Recent technological and conceptual advances have resulted in a plethora of exciting novel engineered adeno associated viral (AAV) vector variants. They all have unique characteristics and abilities. This review summarizes the development and their potential in treating Parkinson's disease (PD). Clinical trials in PD have shown over the last decade that AAV is a safe and suitable vector for gene therapy but that it also is a vehicle that can benefit significantly from improvement in specificity and potency. This review provides a concise collection of the state-of-the-art for synthetic capsids and their utility in PD. We also summarize what therapeutical strategies may become feasible with novel engineered vectors, including genome editing and neuronal rejuvenation.
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| 4. |
- Boman, Andrea, et al.
(author)
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Distinct lysosomal network protein profiles in parkinsonian syndrome cerebrospinal fluid
- 2016
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 6:2, s. 307-315
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Journal article (peer-reviewed)abstract
- Introduction: Clinical diagnosis of parkinsonian syndromes like Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy is hampered by overlapping symptomatology and lack of biomarkers for diagnosis, and definitive diagnosis is only possible post-mortem. Since impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that levels and profiles of lysosomal network proteins in cerebrospinal fluid could be changed in these parkinsonian syndromes.Methods: Cerebrospinal fluid samples were collected from Parkinson’s disease patients (n=18), clinically diagnosed 4-repeat tauopathy patients, corticobasal syndrome (n=6) and progressive supranuclear palsy (n=5), pathologically diagnosed progressive supranuclear palsy (n=8) and corticobasal degeneration patients (n=7). Each patient set was compared to its appropriate control group consisting of the same number of age and gender matched individuals. Lysosomal network protein levels were detected via Western blotting.Results: Lysosomal network proteins have markedly different cerebrospinal fluid protein levels and profiles in Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in Parkinson´s disease; early endosomal antigen 1 was decreased and lysozyme increased in progressive supranuclear palsy; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in corticobasal degeneration.Conclusions: Lysosomal network proteins hold promise of being interesting novel candidates for biomarker studies and for elucidating disease mechanisms of Parkinson’s disease, corticobasal degeneration and progressive supranuclear palsy, but further validation studies will be needed to assess the specificity and the predictive value of these proteins in CSF.
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| 5. |
- de Roos, Paul, et al.
(author)
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A Consensus Set of Outcomes for Parkinson's Disease from the International Consortium for Health Outcomes Measurement
- 2017
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 7:3, s. 533-543
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Journal article (peer-reviewed)abstract
- BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative condition that is expected to double in prevalence due to demographic shifts. Value-based healthcare is a proposed strategy to improve outcomes and decrease costs. To move towards an actual value-based health care system, condition-specific outcomes that are meaningful to patients are essential.OBJECTIVE: Propose a global consensus standard set of outcome measures for PD.METHODS: Established methods for outcome measure development were applied, as outlined and used previously by the International Consortium for Health Outcomes Measurement (ICHOM). An international group, representing both patients and experts from the fields of neurology, psychiatry, nursing, and existing outcome measurement efforts, was convened. The group participated in six teleconferences over a six-month period, reviewed existing data and practices, and ultimately proposed a standard set of measures by which patients should be tracked, and how often data should be collected.RESULTS: The standard set applies to all cases of idiopathic PD, and includes assessments of motor and non-motor symptoms, ability to work, PD-related health status, and hospital admissions. Baseline demographic and clinical variables are included to enable case mix adjustment.CONCLUSIONS: The Standard Set is now ready for use and pilot testing in the clinical setting. Ultimately, we believe that using the set of outcomes proposed here will allow clinicians and scientists across the world to document, report, and compare PD-related outcomes in a standardized fashion. Such international benchmarks will improve our understanding of the disease course and allow for identification of 'best practices', ultimately leading to better informed treatment decisions.
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| 6. |
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| 7. |
- Dorsey, E. Ray, et al.
(author)
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Deep Phenotyping of Parkinson's Disease
- 2020
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 10:3, s. 855-873
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Research review (peer-reviewed)abstract
- Phenotype is the set of observable traits of an organism or condition. While advances in genetics, imaging, and molecular biology have improved our understanding of the underlying biology of Parkinson's disease (PD), clinical pheno-typing of PD still relies primarily on history and physical examination. These subjective, episodic, categorical assessments are valuable for diagnosis and care but have left gaps in our understanding of the PD phenotype. Sensors can provide objective, continuous, real-world data about the PD clinical phenotype, increase our knowledge of its pathology, enhance evaluation of therapies, and ultimately, improve patient care. In this paper, we explore the concept of deep phenotyping-the comprehensive assessment of a condition using multiple clinical, biological, genetic, imaging, and sensor-based tools-for PD. We discuss the rationale for, outline current approaches to, identify benefits and limitations of, and consider future directions for deep clinical phenotyping.
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| 8. |
- Fardell, Camilla, et al.
(author)
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High IQ in Early Adulthood is Associated with Parkinson´s Disease
- 2020
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 10:4, s. 1649-1656
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Journal article (peer-reviewed)abstract
- Background: High education level and high occupational complexity have been implicated as risk factors for Parkinson’s disease (PD). Objective: The objective was to determine whether cognitive capacity, measured as IQ, in early adulthood is associated with the subsequent development of PD. Method: Data on IQ were retrieved from the Swedish Military Service Conscription Registry, comprising Swedish males who enlisted for military service in the period 1968–1993 (N=1,319,235). After exclusion, 1,189,134 subjects in total were included in the present study. Individuals who later developed PD (N=1,724) were identified using the Swedish National Patient Register and the Swedish Cause of Death Register. Results: High education level was associated with PD. High IQ was associated with PD (p<0.0001), both when analyzed as a continuous variable and when divided into three categories. The hazard ratio for the high IQ category compared to the low IQ category was 1.35 (95% confidence interval 1.17–1.55). Strong test results on the subtests, measuring verbal, logic, visuospatial and technical abilities, were also associated with PD. In a subgroup, smoking was inversely associated with PD, as well as with IQ. Conclusions: This study identifies high IQ to be a risk factor for PD.
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| 9. |
- Freidle, M., et al.
(author)
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Implicit Motor Sequence Learning in People with Mild to Moderate Parkinson's Disease: Behavior and Related Brain Function
- 2023
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In: Journal of Parkinsons Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 13:3, s. 367-378
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Journal article (peer-reviewed)abstract
- Background: Deficits in motor learning could be an important explanation for the balance and gait impairments characteristic of people with Parkinson's disease (PD). Empirical studies often report that so-called implicit motor sequence learning is impaired in people with PD, but the results are inconclusive. Altered brain activity during implicit motor sequence learning has also been reported for people with PD in comparison to healthy individuals. Objective: To investigate implicit motor sequence learning and associated neural correlates in individuals with mild to moderate PD. Methods: Fifty-seven participants with PD and 34 healthy participants, all >= 60 years of age, performed the serial reaction time task (SRTT) during the acquisition of functional magnetic resonance imaging (fMRI) data. We analyzed the SRTT as a measure of implicit motor sequence learning in two complementary ways. We analyzed the task-induced fMRI data within regions of interest (ROIs) as well as functional connectivity between ROIs. Results: We found a significant group difference in SRTT performance indicating that the participants with PD had a somewhat lower level of implicit motor sequence learning than the healthy participants. Exploratory analyses suggested that impairments in implicit motor sequence learning for people with PD might be due to a lower learning rate. We did not find any significant group differences in the fMRI data. Conclusion: Our exploratory finding of a lower implicit motor learning rate in PD could have important implications for how people with PD should practice new motor tasks and physical exercise. Future studies need to confirm this finding with hypothesis-driven analyses.
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| 10. |
- Georgiopoulos, Charalampos, et al.
(author)
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Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.
- 2017
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In: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 7:2, s. 301-311
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Journal article (peer-reviewed)abstract
- BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter.OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT.METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions.RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls.CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.
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| 11. |
- Gibson, L. L., et al.
(author)
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Plasma Neurofilament Light and p-tau181 and Risk of Psychosis in Parkinson's Disease
- 2022
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In: Journal of Parkinsons Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 12:5, s. 1527-1538
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Journal article (peer-reviewed)abstract
- Background: Neuropsychiatric symptoms are common and important to people with Parkinson's disease (PD), but their etiology is poorly understood. Plasma neurofilament light (NfL) and p-tau181 are biomarkers of neuro-axonal degeneration and tau pathology respectively, which have yet to be explored in association with the affective and psychotic symptoms in PD. Objective: To investigate the relationship between plasma NfL and p-taul 81 with the affective and psychotic symptoms in PD. Methods: We assessed the baseline concentration of plasma NfL and p-taul 81 in a cohort of 108 patients with PD and 38 healthy controls. A subgroup of patients (n = 63) were assessed annually with clinical measures for up to 7 years. Psychotic symptoms were assessed using the Non-Motor Symptom Scale and affective symptoms were measured in the Hospital Anxiety and Depression Scale. Results: Baseline plasma NfL was a significant predictor of psychotic symptoms longitudinally across the study adjusted for age, Hoehn and Yahr stage, duration of follow up, duration of disease, baseline levodopa and dopamine agonist medication, and baseline cognition: (OR 8.15 [95% CI 1.40-47.4], p =0 .020). There was no association between NfL concentration and the cumulative prevalence of affective symptoms. Plasma p-taul 81 concentration was not associated with psychotic or affective symptoms. Conclusion: These findings suggest psychotic symptoms are associated with greater neurodegeneration in PD. Further studies are needed to explore NfL as a potential biomarker for psychosis in PD.
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| 12. |
- Gonzalez-Robles, Cristina, et al.
(author)
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Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative
- 2023
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In: JOURNAL OF PARKINSONS DISEASE. - 1877-7171 .- 1877-718X. ; 13:6, s. 1013-1035
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Journal article (peer-reviewed)abstract
- Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory ofOMwas created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.
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| 13. |
- Hagell, Peter, et al.
(author)
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Measurement properties of the SF-12 Health Survey in Parkinson's disease
- 2011
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 1:2, s. 185-196
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Journal article (peer-reviewed)abstract
- The 12-item Short-Form Health Survey (SF-12) is an abbreviated version of the SF-36, one of the most widely used patient-reported health outcome rating scales. Similar to the SF-36, it yields summary scores of physical and mental health (PCS and MCS, respectively). However, SF-36 derived PCS and MCS scores have not been found valid in neurological disorders such as Parkinson's disease (PD). Here we used modern psychometric methodology (Rasch analysis) to test the SF-12 in PD, and explored the appropriateness of a total SF-12 score representing overall health. SF-12 data from 150 non-demented people with PD (56% men; mean age/PD-duration, 70/5 years) were analyzed regarding Rasch model fit for the PCS, MCS, as well as for the full SF-12. Data showed some signs of misfit to the Rasch model for all three scales (overall item-trait interaction, P ≥ 0.003; reliability, ≥ 0.85). For example, all scales exhibited signs of dependency between item responses, and the PCS measured with relatively low precision. Model fit (but not measurement precision) was improved following deletion of one PCS and one MCS item (overall item-trait interaction, P ≥ 0.387; reliability, ≥ 0.82). These observations suggest that the SF-12 can be used as a coarse health survey tool in PD and that a total SF-12 may be useful as a measure of overall health. However, its appropriateness as an outcome measure can be questioned and it is somewhat unclear exactly what the derived scores represent. As such, the SF-12 should probably be considered an assessment tool (or index) rather than a measurement instrument.
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| 14. |
- Hagell, Peter, et al.
(author)
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Measurement Properties of the SF-12 Health Survey in Parkinson's Disease
- 2011
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-718X .- 1877-7171. ; 1:2, s. 185-196
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Journal article (peer-reviewed)abstract
- The 12-item Short-Form Health Survey (SF-12) is an abbreviated version of the SF-36, one of the most widely used patient-reported health outcome rating scales. Similar to the SF-36, it yields summary scores of physical and mental health (PCS and MCS, respectively). However, SF-36 derived PCS and MCS scores have not been found valid in neurological disorders such as Parkinson's disease (PD). Here we used modern psychometric methodology (Rasch analysis) to test the SF-12 in PD, and explored the appropriateness of a total SF-12 score representing overall health. SF-12 data from 150 non-demented people with PD (56% men; mean age/PD-duration, 70/5 years) were analyzed regarding Rasch model fit for the PCS, MCS, as well as for the full SF-12. Data showed some signs of misfit to the Rasch model for all three scales (overall item-trait interaction, P >= 0.003; reliability, >= 0.85). For example, all scales exhibited signs of dependency between item responses, and the PCS measured with relatively low precision. Model fit (but not measurement precision) was improved following deletion of one PCS and one MCS item (overall item-trait interaction, P >= 0.387; reliability, >= 0.82). These observations suggest that the SF-12 can be used as a coarse health survey tool in PD and that a total SF-12 may be useful as a measure of overall health. However, its appropriateness as an outcome measure can be questioned and it is somewhat unclear exactly what the derived scores represent. As such, the SF-12 should probably be considered an assessment tool (or index) rather than a measurement instrument.
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| 15. |
- Hariz, Gun-Marie, et al.
(author)
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"DBS means everything - for some time" : Patients' Perspectives on Daily Life with Deep Brain Stimulation for Parkinson's Disease
- 2016
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In: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 6:2, s. 335-347
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Journal article (peer-reviewed)abstract
- Background: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. However, patients' own perceptions of the impact of DBS on their daily living is not fully explored. Objective: We aimed to collect and analyse patients' narratives about their everyday experiences of being on chronic DBS. Methods: Semi-structured interviews with open-ended questions were conducted with 42 patients (11 women) who had been on DBS for a mean of three years. The questions were related to patients' ordinary daily life and eventual changes, both negative and positive, brought about by DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in grounded theory. Results: From the patients' narratives the core category `DBS means everything - for some time' was established, and supported by the following categories: 1) Relief from invasive tremor. 2) A rescue from cramps and pain. 3) Easier movement swings and more predictable living space. 4) Hard, but compared to previous suffering, bearable adverse events. 5) Parkinson's disease is progressing despite DBS. Conclusions: The analysis of the participants' narratives shed light on patients' unique perceptions and perspectives of the impact of DBS on their everyday lives. Patients with advanced PD highly appreciated the positive impact of DBS on their daily life even if this impact is limited in time. For the majority, the relief from the severe parkinsonian symptoms, especially tremor and painful cramps, outweighed the side effects of DBS. The study provided information not readily captured by pre-formulated questionnaires and scales.
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| 16. |
- Hariz, Marwan
(author)
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My 25 Stimulating Years with DBS in Parkinson's Disease
- 2017
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In: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 7, s. S35-S43
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Research review (peer-reviewed)abstract
- The year 2017 marks the 30th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid, Pollak et al. in 1987, initially targeting the motor thalamus to treat tremor, and subsequently targeting the subthalamic nucleus (STN) for treatment of symptoms of advanced Parkinson's disease (PD). STN DBS is undoubtedly "the most important discovery since levodopa", as stated by David Marsden in 1994. In 2014, The Lasker-DeBakey Clinical Medical Research Award to "honor two scientists who developed deep brain stimulation of the subthalamic nucleus", was bestowed upon Benabid and DeLong. STN DBS remains today the main surgical procedure for PD, due to its effectiveness in ameliorating PD symptoms and because it is the only surgical procedure for PD that allows a radical decrease in medication. Future improvements of DBS include the possibility to deliver a "closed-loop", "on demand" stimulation, as highly preliminary studies suggest that it may improve both axial and appendicular symptoms and reduce side effects such as dysarthria. Even though DBS of the subthalamic nucleus is the main surgical procedure used today for patients with PD, all patients are not suitable for STN DBS; as a functional neurosurgeon performing since more than 25 years various surgical procedures the aim of which is not to save life but to improve the patient's quality of life, I consider that the surgery should be tailored to the patient's individual symptoms and needs, and that its safety is paramount.
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| 17. |
- Hug, Kristina
(author)
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Bringing Advanced Therapies for Parkinson's Disease to the Clinic : An Analysis of Ethical Issues
- 2021
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:s2, s. 147-153
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Research review (peer-reviewed)abstract
- Advanced therapies for Parkinson's disease (PD) constitute a broad range of treatments, each presenting specific ethical challenges. Some of these therapies are established and in clinical use, like device-aided therapies, and others, based on advanced therapeutic medicinal products (ATMPs), are still in early stage of clinical trials. This paper focuses on some common ethical issues arising in these two categories of advanced therapies, especially challenges arising when advanced therapies are proposed to PD patients in the form of advanced care, under a clinical trial, or, in case of ATMPs, under the 'hospital exemption' rule. The ethical issues covered here relate mainly to ensuring informed consent in these different contexts, to the stakeholder role of patient's non-professional caretakers, such as family, and to patient safety in treatments under 'hospital exemption'. To illustrate the points discussed in connection with 'hospital exemption' rule, the example of the EU has been chosen. This paper does not claim completeness of ethical issues raised by bringing advanced therapies for PD to the clinic, but rather presents examples of ethical challenges in this context.
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| 18. |
- Kraepelien, Martin, et al.
(author)
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Individually Tailored Internet-Based Cognitive-Behavioral Therapy for Daily Functioning in Patients with Parkinsons Disease : A Randomized Controlled Trial
- 2020
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 10:2, s. 653-664
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Journal article (peer-reviewed)abstract
- Background: Parkinson's disease (PD) is often associated with psychological distress and lowered daily functioning. The availability of psychological interventions tailored for people with Parkinson is very limited. Objective: To study if guided individually-tailored internet-based cognitive behavioral therapy (ICBT) provide additional value to standard medical treatment for PD. Methods: Seventy-seven individuals with PD and self-reported problems with general function measured with the Work and Social Adjustment Scale (WSAS > 15) were randomized to 10 weeks of either ICBT combined with standard medical treatment, or standard medical treatment plus being on waitlist to ICBT (CONTROL). Change in the main outcome WSAS, as well as secondary measures such as quality of life, depression, anxiety and insomnia symptoms were investigated post treatment. Results: Participants receiving ICBT reported significantly higher functioning after treatment (WSAS group difference -4.56, controlled effect size g = 0.69, significant group by time interaction, W.2 = 26.23, p = 0.001). However, only around one third of participants in the treatment group were classified as treatment responders, defined as having a 30% reduction on the WSAS post treatment. Patient involvement and ratings of ICBT credibility were high. Symptoms of anxiety, depression and insomnia symptoms were significantly lower after treatment compared to CONTROL. There were also positive effects on Parkinson-specific function and quality of life in the treatment group. Conclusions: ICBT as an addition to standard medical treatment was credible and improved functioning for some individuals with PD. Still, the treatment needs further development in order to help a larger proportion of individuals with PD. Trial registration number: ClinicalTrials.gov NCT02627885.
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| 19. |
- Lenfeldt, Niklas, et al.
(author)
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Fractional Anisotropy and Mean Diffusion as Measures of Dopaminergic Function in Parkinson's Disease : Challenging Results
- 2017
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In: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 7:1, s. 129-142
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Journal article (peer-reviewed)abstract
- Background: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson’s disease.Objective: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT.Methods: One-hundred and eleven patients with Parkinson’s disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13). Four equipment combinations of MRI scanners/SPECT gamma cameras were used during the study. Data from each combination were analyzed separately. Regions-of-interest were outlined in the substantia nigra (three subareas, DTI only) and in the striatum (putamen and caudate). Side differences and bilateral averages were correlated using linear regression. The significance threshold was set at P < 0.001 and 0.001 < P< 0.05 was defined as a trend towards significance.Results: For side differences, no significant correlations were observed, but in patients, there was a trend towards a negative correlation between MD in the middle nigra and putaminal DAT uptake in two combinations (P = 0.04 and P = 0.03). For averages, in patients, striatal MD correlated negatively with striatal DAT uptake in one combination (P = 0.0005) and trended towards negative correlations with striatal D2R uptake (one combination, P = 0.03) and with the sum of striatal DAT and D2R uptake (two combinations P = 0.002 and P = 0.03). FA showed no correlations in patients, and no correlations were found in controls.Conclusions: The poor correlations between MD and dopamine activity –and absent correlations for FA – imply that additional diffusion measures must be developed to reliably assess the dopaminergic degeneration in Parkinson’s disease.
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| 20. |
- Lindgren, Hanna S., et al.
(author)
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Putaminal Upregulation of FosB/ΔFosB-Like Immunoreactivity in Parkinson's Disease Patients with Dyskinesia
- 2011
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 1:4, s. 347-357
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Journal article (peer-reviewed)abstract
- The transcription factor FosB is a mediator of maladaptive neuroplasticity in animal models of Parkinson´s disease (PD) and L-DOPA-induced dyskinesia. Using an antibody that recognizes all known isoforms of FosB and FosB, we have examined the expression of these proteins in post-mortem basal ganglia sections from PD patients. The patient cases were classified as being dyskinetic or non-dyskinetic based on their clinical records. Sections from neurologically healthy controls were also included in the study. Compared to both controls and non-dyskinetic cases, the dyskinetic group showed a higher density of FosB/ FosB-immunopositive cells in the posterior putamen, which represents the motor region of the striatum in primates. In contrast, the number of FosB/ FosB-positive cells did not differ significantly among the groups in the caudate, a region primarily involved with the processing of cognitive and limbic-related information. Only sparse FosB/ FosB immunoreactivity was found in the in the pallidum externum and internum, and no significant group differences were detected in these nuclei. The putaminal elevation of FosB/ FosB-like immunoreactivity in patients who had been affected by L-DOPA-induced dyskinesia is consistent with results from both rat and non-human primate models of this movement disorder. The present findings support the hypothesis of an involvement of FosB-related transcription factors in the molecular mechanisms of L-DOPA-induced dyskinesia.
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| 21. |
- Maple-Grødem, Jodi, et al.
(author)
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Lack of Association between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts
- 2021
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:4, s. 1569-1578
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Journal article (peer-reviewed)abstract
- Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson's disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population.Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD.Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models.Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43).Conclusion: This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.
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| 22. |
- Mitra, Reinika, et al.
(author)
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Local Change in Urinary Bladder Contractility Following CNS Dopamine Denervation in the 6-OHDA Rat Model of Parkinson's Disease
- 2015
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In: Journal of Parkinsons Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 5:2, s. 301-311
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Journal article (peer-reviewed)abstract
- Background: Urinary problems, including urinary frequency, urgency, and nocturia are some of the non-motor symptoms that correlate most with poor quality of life in Parkinson's disease. However, the mechanism behind these symptoms is poorly understood, in particular regarding peripheral bladder pathophysiology following dopamine degeneration. Objective: In this study, we compared the contractile responsiveness of urinary bladder from the 6-OHDA unilateral rat model of Parkinson's disease with that of normal untreated animals. Methods: The contractility of the urinary detrusor muscle was evaluated in bladder strip preparations using electrical field stimulation, and muscarinic and purinoceptor stimulations in an vitro organ bath setup. Results: Our data show that the overall contractile response following electrical field stimulation was significantly higher (43% at maximum contraction by 20-40 Hz stimulation) in the 6-OHDA-lesioned rats as compared to control animals. This increase was associated with a significant increase in the cholinergic contractile response, where the muscarinic agonist methacholine produced a 44% (at 10(-4) Mconcentration) higher response in the 6-OHDA-treated rats as compared to controls with a significant left-shift of the dose response. This indicates an altered sensitivity of the muscarinic receptor system following the specific central 6-OHDA-induced dopamine depletion. In addition a 36% larger contraction of strips from the 6-OHDA animals was also observed with purinoceptor activation using the agonist ATP (5x10(-3) M) during atropine treatment. Conclusions: Our data shows that it is not only the central dopamine control of the micturition reflex that is altered in Parkinson's disease, but also the local contractile function of the urinary bladder. The current study draws attention to a mechanism of urinary dysfunction in Parkinson's disease that has previously not been described.
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| 23. |
- Nyholm, Dag, et al.
(author)
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Effects of Helicobacter pylori on Levodopa Pharmacokinetics
- 2021
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In: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 11:1, s. 61-69
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Research review (peer-reviewed)abstract
- Background:Infection with Helicobacter pylori seems overrepresented in Parkinson’s disease. Clinical observations suggest a suboptimal treatment effect of levodopa in Helicobacter positive patients.Objective:Describe and explain the connection between a Helicobacter pylori infection of the upper gut and changes in pharmacokinetics of oral levodopa treatment in Parkinson’s disease.Methods:PubMed, Google Scholar, and Cross Reference search was done using the key words and combined searches: Bioavailability, drug metabolism, dyskinesia, Helicobacter, L-dopa, levodopa, motor control, pharmacodynamics, pharmacokinetics, prevalence, unified Parkinson’s disease rating scale.Results:The prevalence of Helicobacter pylori in Parkinson’s disease patients is reported to be about 1.6-fold higher than in a control population in some studies. Helicobacter has therefore been assumed to be linked to Parkinson’s disease, but the mechanism is unclear. As regards symptoms and treatment, patients with Parkinson’s disease on levodopa therapy and with Helicobacter pylori infection display worse motor control than those without Helicobacter infection. Eradication of the infection improves levodopa response in Parkinson’s disease, likely as a consequence of an increased oral pre-systemic bioavailability of levodopa, likely to be explained by reduced Helicobacter-dependent levodopa consumption in the stomach. In addition, small intestinal bacterial overgrowth may also have an impact on the therapeutic setting for levodopa treatment but is less well established.Conclusion:Eradication of Helicobacter pylori improves levodopa bioavailability resulting in improved motor control. Eradication of Helicobacter should be considered in patients with poor symptomatic control and considerable motor fluctuations.
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| 24. |
- Nyholm, Dag, et al.
(author)
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Real-Life Use of Levodopa/Carbidopa Intestinal Gel in Parkinson's Disease According to Analysis of Pump Data
- 2020
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In: Journal of Parkinson's Disease. - : IOS PRESS. - 1877-7171 .- 1877-718X. ; 10:4, s. 1529-1534
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Journal article (peer-reviewed)abstract
- Background: Levodopa/carbidopa intestinal gel (LCIG) infusion is an efficacious treatment of motor and non-motor fluctuations in people with Parkinson's disease (PD). Real-life use of the treatment is not previously studied.Objective: The aims of the study were to explore the use of LCIG and to determine how extra doses of LCIG are used in daily life.Methods: Twenty-five PD patients with ongoing LCIG therapy were consecutively included. Pump data was retrieved from 30 days on average, by means of software, extracting the most recent pump events.Results: The daily duration of infusion was 15 hours on average, in 18 patients, whereas the remaining 7 patients used 24-hour infusion. Morning doses ranged from 38-190 mg levodopa, for patients who utilized this function. Median number of daily extra doses was 2.5 (range: 0-10.6) and median size of the extra dose was 24 mg (0-80 mg) levodopa. Median total daily levodopa intake with LCIG was 1201 mg (range: 417-2322 mg).Conclusion: Retrieving pump data is possible and may be important for evaluating the at-home use of LCIG, to optimize the therapy. Adherence to treatment should be monitored, which is not technically difficult, at least in device-aided treatments for PD.
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| 25. |
- Olsson, Tomas T., et al.
(author)
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Delayed Clinical Manifestation of Parkinson's Disease Among Physically Active : Do Participants in a Long-Distance Ski Race Have a Motor Reserve?
- 2020
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In: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 10:1, s. 267-274
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Journal article (peer-reviewed)abstract
- BACKGROUND: Physical activity is associated with reduced risk of Parkinson's disease (PD). The explanations for this association are not completely elucidated. We use long-term PD-incidence data from long-distance skiers to study the relationship between exercise and PD.OBJECTIVE: We aimed to investigate if physical activity is associated with long-term lower risk of PD and if this association could be explained by physically active people being able to sustain more PD neuropathology before clinical symptoms, a motor reserve.METHODS: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685), exhibited reduced incidence of PD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years).RESULTS: Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of PD (HR: 0.71; 95 % CI 0.56-0.90) compared to non-skiers. When reducing risk for reverse causation by excluding PD cases within the first five years from race participation, there was still a trend for lower risk of PD (HR: 0.80; 95 % CI 0.62-1.03). Further, the PD prevalence converged between skiers and non-skiers after 15 years of follow-up, which is more consistent with a motor reserve in the physically active rather than neuroprotection.CONCLUSIONS: A physical active lifestyle is associated with reduced risk for PD. This association weakens with time and might be explained by a motor reserve among the physically active.
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