| 1. |
- Ayton, Scott, et al.
(författare)
-
The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders
- 2022
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:5, s. 993-1003
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson’s disease with dementia (PDD) (29). Results: CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. Conclusions: These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility.
|
|
| 2. |
- Cenci, M. Angela, et al.
(författare)
-
Dyskinesia matters
- 2020
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:3, s. 392-396
-
Tidskriftsartikel (refereegranskat)abstract
- Levodopa-induced dyskinesia (LID) represents a significant source of discomfort for people with Parkinson's disease (PD). It negatively affects quality of life, it is associated with both motor and nonmotor fluctuations, and it brings an increased risk of disability, balance problems, and falls. Although the prevalence of severe LID appears to be lower than in previous eras (likely owing to a more conservative use of oral levodopa), we have not yet found a way to prevent the development of this complication. Advanced surgical therapies, such as deep brain stimulation, ameliorate LID, but only a minority of PD patients qualify for these interventions. Although some have argued that PD patients would rather be ON with dyskinesia than OFF, the deeper truth is that patients would very much prefer to be ON without dyskinesia. As researchers and clinicians, we should aspire to make that goal a reality. To this end, translational research on LID is to be encouraged and persistently pursued.
|
|
| 3. |
- Dayal, Viswas, et al.
(författare)
-
Short Versus Conventional Pulse-Width Deep Brain Stimulation in Parkinson's Disease : A Randomized Crossover Comparison
- 2020
-
Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 35:1, s. 101-108
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN-DBS patients has not been evaluated. Objective To compare the effect of short PW settings using 30-mu s with conventional 60-mu s settings on stimulation-induced dysarthria in Parkinson's disease patients with previously implanted STN-DBS systems.Methods: In this single-center, double-blind, randomized crossover trial, we assigned 16 Parkinson's disease patients who had been on STN-DBS for a mean of 6.5 years and exhibited moderate dysarthria to 30-mu s or 60-mu s settings for 4 weeks followed by the alternative PW setting for a further 4 weeks. The primary outcome was difference in dysarthric speech measured by the Sentence Intelligibility Test between study baseline and the 2 PW conditions. Secondary outcomes included motor, nonmotor, and quality of life measures.Results: There was no difference in the Sentence Intelligibility Test scores between baseline and the 2 treatment conditions (P = 0.25). There were also no differences noted in motor, nonmotor, or quality of life scores. The 30-mu s settings were well tolerated, and adverse event rates were similar to those at conventional PW settings. Post hoc analysis indicated that patients with dysarthria and a shorter duration of DBS may be improved by short PW stimulation.Conclusions: Short PW settings using 30 mu s did not alter dysarthric speech in chronic STN-DBS patients. A future study should evaluate whether patients with shorter duration of DBS may be helped by short PW settings.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Espa, Elena, et al.
(författare)
-
Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia
- 2023
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 38:3, s. 410-422
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Current models of levodopa (L-dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L-dopa. However, patients with LID receive combination therapies that often include dopamine agonists.OBJECTIVE: Using 6-hydroxydopamine-lesioned rats as a model, we aimed to establish whether an adjunct treatment with the D2/3 agonist ropinirole impacts on patterns of LID-related neuroplasticity and drug responses.METHODS: Different regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment were compared using measures of hypokinesia and dyskinesia. Striatal expression of ∆FosB and angiogenesis markers were studied immunohistochemically. Antidyskinetic effects of different drug categories were investigated in parallel groups of rats receiving either L-dopa monotreatment or L-dopa combined with ropinirole.RESULTS: We defined chronic regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment inducing overall similar abnormal involuntary movement scores. Compared with the monotreatment group, animals receiving the L-dopa-ropinirole combination exhibited an overall lower striatal expression of ∆FosB with a distinctive compartmental distribution. The expression of angiogenesis markers and blood-brain barrier hyperpermeability was markedly reduced after L-dopa-ropinirole cotreatment compared with L-dopa monotreatment. Moreover, significant group differences were detected upon examining the response to candidate antidyskinetic drugs. In particular, compounds modulating D1 receptor signaling had a stronger effect in the L-dopa-only group, whereas both amantadine and the selective NMDA antagonist MK801 produced a markedly larger antidyskinetic effect in L-dopa-ropinirole cotreated animals.CONCLUSIONS: Cotreatment with ropinirole altered LID-related neuroplasticity and pharmacological response profiles. The impact of adjuvant dopamine agonist treatment should be taken into consideration when investigating LID mechanisms and candidate interventions in both clinical and experimental settings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
| 7. |
|
|
| 8. |
- Fasano, A., et al.
(författare)
-
Gaps, Controversies, and Proposed Roadmap for Research in Normal Pressure Hydrocephalus
- 2020
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:11, s. 1945-1954
-
Tidskriftsartikel (refereegranskat)abstract
- Idiopathic normal pressure hydrocephalus is considered common but remains underinvestigated. There are no uniformly accepted diagnostic criteria and therapeutic guidelines. We summarize the accumulated evidence regarding the definition, pathophysiology, diagnosis, and treatment of idiopathic normal pressure hydrocephalus, highlighting the many gaps and controversies, including diagnostic challenges, the frequent association with neurodegeneration and vascular disease, and the many unknowns regarding patient selection and outcome predictors. A roadmap to fill these gaps and solve the controversies around this condition is also proposed. More evidence is required with respect to diagnostic criteria, the value of ancillary testing, prospective population-based studies and novel trial designs. Furthermore, a need exists to develop new advanced options in shunt technology. (c) 2020 International Parkinson and Movement Disorder Society
|
|
| 9. |
- Fazio, P, et al.
(författare)
-
Corrigendum
- 2020
-
Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 35:12, s. 2363-2364
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Gonzalez-Robles, Cristina, et al.
(författare)
-
Embedding Patient Input in Outcome Measures for Long-Term Disease-Modifying Parkinson Disease Trials
- 2024
-
Ingår i: Movement Disorders. - 0885-3185 .- 1531-8257. ; 39:2, s. 433-438
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients. Objectives: The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years. Methods: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures. A larger PPIE group provided input on their key considerations for such an endpoint. Feasibility, clinimetric properties, and relevance to patients were assessed and synthesized. Results: Although initial considerations favored the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in Off, feasibility, PPIE input, and clinimetric properties supported the MDS-UPDRS Part II. However, PPIE input also highlighted the importance of nonmotor symptoms, especially in the longer term, leading to the selection of the MDS-UPDRS Parts I + II sum score. Conclusions: The MDS-UPDRS Parts I + II sum score was chosen as the primary outcome for large 3-year disease-modification trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
| 13. |
- Grenn, Francis P., et al.
(författare)
-
The Parkinson's Disease Genome-Wide Association Study Locus Browser
- 2020
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus. Methods: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data. Results: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets. Conclusions: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered.
|
|
| 14. |
- Grimm, Max Joseph, et al.
(författare)
-
Clinical Conditions “Suggestive of Progressive Supranuclear Palsy”—Diagnostic Performance
- 2020
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:12, s. 2301-2313
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Movement Disorder Society diagnostic criteria for progressive supranuclear palsy introduced the diagnostic certainty level “suggestive of progressive supranuclear palsy” for clinical conditions with subtle signs, suggestive of the disease. This category aims at the early identification of patients, in whom the diagnosis may be confirmed as the disease evolves. Objective: To assess the diagnostic performance of the defined clinical conditions suggestive of progressive supranuclear palsy in an autopsy-confirmed cohort. Methods: Diagnostic performance of the criteria was analyzed based on retrospective clinical data of 204 autopsy-confirmed patients with progressive supranuclear palsy and 216 patients with other neurological diseases. Results: The conditions suggestive of progressive supranuclear palsy strongly increased the sensitivity compared to the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. Within the first year after symptom onset, 40% of patients with definite progressive supranuclear palsy fulfilled criteria for suggestive of progressive supranuclear palsy. Two-thirds of patients suggestive of progressive supranuclear palsy evolved into probable progressive supranuclear palsy after an average of 3.6 years. Application of the criteria for suggestive of progressive supranuclear palsy reduced the average time to diagnosis from 3.8 to 2.2 years. Conclusions: Clinical conditions suggestive of progressive supranuclear palsy allow earlier identification of patients likely to evolve into clinically possible or probable progressive supranuclear and to have underlying progressive supranuclear palsy pathology. Further work needs to establish the specificity and positive predictive value of this category in real-life clinical settings, and to develop specific biomarkers that enhance their diagnostic accuracy in early disease stages.
|
|
| 15. |
- Grover, Sandeep, et al.
(författare)
-
Replication of a Novel Parkinson's Locus in a European Ancestry Population
- 2021
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:7, s. 1689-1695
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recently published East Asian genome-wide association study of Parkinson;s disease (PD) reported 2 novel risk loci, SV2C and WBSCR17.OBJECTIVES: The objective of this study were to determine whether recently reported novel SV2C and WBSCR17 loci contribute to the risk of developing PD in European and East Asian ancestry populations.METHODS: We report an association analysis of recently reported variants with PD in the COURAGE-PD cohort (9673 PD patients; 8465 controls) comprising individuals of European and East Asian ancestries. In addition, publicly available summary data (41,386 PD patients; 476,428 controls) were pooled.RESULTS: Our findings confirmed the role of the SV2C variant in PD pathogenesis (rs246814, COURAGE-PD PEuropean = 6.64 × 10-4 , pooled PD P = 1.15 × 10-11 ). The WBSCR17 rs9638616 was observed as a significant risk marker in the East Asian pooled population only (P = 1.16 × 10-8 ).CONCLUSIONS: Our comprehensive study provides an up-to-date summary of recently detected novel loci in different PD populations and confirmed the role of SV2C locus as a novel risk factor for PD irrespective of the population or ethnic group analyzed. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
| 16. |
- Grötsch, Marie Therese, et al.
(författare)
-
A Modified Progressive Supranuclear Palsy Rating Scale
- 2021
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:5, s. 1203-1215
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. Objective: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. Methods: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. Results: The modified scale retained 14 items (yielding 0–2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). Conclusions: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine.
|
|
| 17. |
|
|
| 18. |
- Hall, Sara, et al.
(författare)
-
Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders
- 2020
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:3, s. 513-518
-
Tidskriftsartikel (refereegranskat)abstract
- Background: CSF concentration of neurogranin has been suggested as a biomarker for synapse dysfunction. Objectives: To investigate CSF neurogranin in parkinsonian disorders compared to controls and Alzheimer's disease and the possible correlations between neurogranin and cognitive and motor impairment. Methods: We included 157 patients with PD, 29 with PD with dementia, 11 with dementia with Lewy bodies, 26 with MSA, 21 with PSP, 6 with corticobasal syndrome, 47 controls, and 124 with Alzheimer's disease. CSF neurogranin was measured using two enzyme-linked immunosorbent assays; from EUROIMMUN and the University of Gothenburg. Results: We found a strong correlation between CSF neurogranin-EI and CSF neurogranin–University of Gothenburg (Rs = 0.890; P < 0.001). Neurogranin was decreased in PD, PD with dementia, MSA, and PSP compared to controls and Alzheimer's disease. Neurogranin did not correlate with motor or cognitive impairment, longitudinal decline, or progression to dementia in PD. Conclusions: CSF neurogranin is decreased in parkinsonian disorders compared to controls, emphasizing the importance of synaptic dysfunction in these disorders.
|
|
| 19. |
- Hall, Sara, et al.
(författare)
-
Plasma Phospho-Tau Identifies Alzheimer's Co-Pathology in Patients with Lewy Body Disease
- 2021
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:3, s. 767-771
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease co-pathology is common in dementia with Lewy bodies and Parkinson's disease with dementia (Lewy body disease) and can reliably be detected with positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Recently developed blood biomarkers are more accessible and less expensive alternatives. Objective: To investigate if plasma phospho-tau217 and phospho-tau181 can detect Alzheimer's pathology in Lewy body disease with dementia. Methods: In this cross-sectional study we investigated plasma phospho-tau217 and phospho-tau181 in 35 patients with Lewy body disease with dementia. Patients underwent tau-PET imaging (18F-RO948). Results: Plasma phospho-tau217 correlated with plasma phospho-tau181, CSF phospho-tau217 (rs = 0.68, P < 0.001), and negatively with CSF β-amyloid42/40 (rs = −0.52, P = 0.001). Plasma phospho-tau217 and phospho-tau181 correlated with tau-PET signal in the temporal cortex (rs > 0.56, P < 0.001) and predicted abnormal tau-PET status and β-amyloid status (area under the curve > 0.78 and > 0.81, respectively). Conclusion: Plasma phospho-tau might be a useful marker for Alzheimer's co-pathology in Lewy body disease with dementia.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Huber, Maria, et al.
(författare)
-
Metabolic correlates of dopaminergic loss in dementia with lewy bodies
- 2020
-
Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
-
Tidskriftsartikel (refereegranskat)abstract
- Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
|
|
| 29. |
- Huttunen, Henri J., et al.
(författare)
-
Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial
- 2023
-
Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 38:7, s. 1209-1222
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18F]FE-PE2I. Results: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
| 30. |
- Huynh, Benjamin, et al.
(författare)
-
Comparison of Locus Coeruleus Pathology with Nigral and Forebrain Pathology in Parkinson's Disease
- 2021
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:9, s. 2085-2093
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pathology in the noradrenergic A6 locus coeruleus has not been compared with more rostral dopaminergic A9 substantia nigra and A10 ventral tegmental area, and cholinergic Ch4 basal nucleus and Ch1/2 septal regions in the same cases of Parkinson's disease (PD). Objective: To determine whether there is a gradient of caudal to rostral cell loss in PD. Methods: Postmortem brains were collected from longitudinally followed donors with PD (n = 14) and aged-matched healthy donors (n = 13), six with restricted brainstem Lewy pathology (RLP), fixed in formalin and serial tissue slabs processed for cell and pathological quantitation. Noradrenergic A6 neurons were assessed and compared with previously published midbrain and basal forebrain data. From these data, regression estimates of pathological onset and progression were determined. Results: Restricted Lewy pathology (RLP) cases had high pathological variability but no significant reduction in neurons. Pathology containing A6 neuron loss started at PD diagnosis and progressed faster (2.4% p.a) than the loss of dopaminergic A9 neurons (2% loss p.a.). Cases with dementia had significantly more pathology in noradrenergic and cholinergic neurons, had greater noradrenergic A6 neuron loss (29% more, progressing at 3.2% p.a.), and a selective loss of lateral A10 nonmelanized dopamine-producing neurons (starting a decade following diagnosis). Conclusions: These findings show that in the same Parkinson's disease cases cell loss in these neurotransmitter systems does not follow a strict caudal to rostral trajectory and suggests symptom onset may relate to substantial pathology in the noradrenergic A6 locus coeruleus neurons in people with reduced dopamine-producing A9 substantia nigra neurons.
|
|
| 31. |
- Isomura, Kayoko, et al.
(författare)
-
Insomnia in Tourette Syndrome and Chronic Tic Disorder
- 2022
-
Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 37:2, s. 392-400
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insomnia is common in Tourette syndrome (TS) and chronic tic disorder (CTD), but precise prevalence estimates are lacking.OBJECTIVE: In this Swedish register-based cohort study, we estimated the prevalence of insomnia in TS/CTD and quantified the magnitude of this association, accounting for familial confounders and relevant somatic and psychiatric comorbidities.METHODS: Of 10,444,702 individuals living in Sweden during the period from 1997 to 2013, 5877 had a diagnosis of TS/CTD and were compared to unexposed individuals from the general population on the presence of insomnia using logistic regression models.RESULTS: Individuals with TS/CTD had a period prevalence of insomnia of 32.16%, compared to 13.70% of the unexposed population. This translated into a 6.7-fold increased likelihood of insomnia in TS/CTD (odds ratio adjusted [aOR] for sex, birth year, birth country, and somatic disorders = 6.74; 95% confidence interval [CI], 6.37-7.15). A full sibling comparison, designed to adjust for shared familial factors, attenuated the estimates (aOR = 5.41; 95% CI, 4.65-6.30). When individuals with attention-deficit/hyperactivity disorder (ADHD) and pervasive developmental disorders were excluded, the association was also attenuated, whereas exclusion of other psychiatric comorbidities had minimal impact. Having persistent TS/CTD, comorbid ADHD, and taking ADHD medication greatly increased the likelihood of insomnia.CONCLUSIONS: Insomnia is significantly associated with TS/CTD, independently from somatic disorders, familial factors or psychiatric comorbidities, although familial factors, neurodevelopmental comorbidities, and ADHD/ADHD medication may explain part of the association. Insomnia should be routinely assessed and managed in TS/CTD, particularly in chronic patients and in those with comorbid ADHD. Other sleep disorders require further study. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
| 32. |
|
|
| 33. |
- Jost, Stefanie T., et al.
(författare)
-
Levodopa Dose Equivalency in Parkinson's Disease : Updated Systematic Review and Proposals
- 2023
-
Ingår i: Movement Disorders. - 0885-3185. ; 38:7, s. 1236-1252
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as ‘levodopa equivalent dose’ (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. Objectives: To update LED conversion formulae based on a systematic review. Methods: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. Results: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. Conclusions: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD.
|
|
| 34. |
|
|
| 35. |
- Kang, Xiaoying, et al.
(författare)
-
Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
- 2021
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 96:15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD.Objective: This study aimed to examine the association of MC with PD risk.Methods: In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (N-MC/N-Sibling = 6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.Results: During a mean follow-up of similar to 7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Koens, Lisette H, et al.
(författare)
-
A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism
- 2023
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 38:4, s. 646-653
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy-to-use clinical screening tool to help recognize movement disorders.OBJECTIVE: The aim is to develop a user-friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs.METHODS: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter-rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool.RESULTS: A movement disorder was rated as present in 80% of the patients, with a moderate inter-rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter-rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool.CONCLUSIONS: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Kruse, Christopher, et al.
(författare)
-
Care of Late-Stage Parkinsonism : Resource Utilization of the Disease in Five European Countries
- 2024
-
Ingår i: Movement Disorders. - 0885-3185. ; 39:3, s. 571-584
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. Objective: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. Methods: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. Results: During the 3-month period, the costs were €20,573 (France), €19,959 (Germany), €18,319 (the Netherlands), €25,649 (Sweden), and €12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. Conclusion: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned.
|
|
| 42. |
- Kühnel, Line, et al.
(författare)
-
Disease Progression in Multiple System Atrophy—Novel Modeling Framework and Predictive Factors
- 2022
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:8, s. 1719-1727
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course. Objectives: The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease. Methods: The disease-progression model estimated a population-level progression trajectory of subscales of the Unified MSA Rating Scale and the Unified Parkinson's Disease Rating Scale using patients in the European MSA natural history study. The predicted disease continuum was validated via multiple analyses based on reported anchor points, and the effect of MSA subtype on the rate of disease progression was evaluated. Results: The predicted disease continuum spanned approximately 6 years, with an estimated average duration of 51 months for a patient with global disability score 0 to reach the highest level of 4. The predicted continuous disease stages were shown to be correlated with time of symptom onset and predictive of survival time. MSA motor subtype was found to significantly affect disease progression, with MSA-parkinsonian (MSA-P) type patients having an accelerated rate of progression. Conclusions: The proposed modeling framework introduces a new method of analyzing and interpreting the progression of MSA. It can provide new insights and opportunities for investigating covariate effects on the rate of progression and provide well-founded predictions of patient-level future progressions.
|
|
| 43. |
|
|
| 44. |
- Lerche, S., et al.
(författare)
-
CSF Protein Level of Neurotransmitter Secretion, Synaptic Plasticity, and Autophagy in PD and DLB
- 2021
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:11, s. 2595-2604
-
Tidskriftsartikel (refereegranskat)abstract
- Background Molecular pathways associated with alpha-synuclein proteostasis have been detected in genetic studies and in cell models and include autophagy, ubiquitin-proteasome system, mitochondrial homeostasis, and synaptic plasticity. However, we lack biomarkers that are representative for these pathways in human biofluids. Objective The objective of this study was to evaluate CSF protein profiles of pathways related to alpha-synuclein proteostasis. Methods We assessed CSF protein profiles associated with neurotransmitter secretion, synapse plasticity, and autophagy in 2 monocentric cohorts with alpha-synucleinopathy (385 PD patients and 67 DLB patients). We included 80 PD patients and 17 DLB patients with variants in the glucocerebrosidase gene to serve as proxy for accelerated alpha-synuclein pathology with pronounced clinical trajectories. Results (1) Proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy were lower in PD and DLB patients compared with healthy controls. (2) These patterns were more pronounced in DLB than in PD patients, accentuated by GBA variant status in both entities. (3) CSF levels of these proteins were positively associated with CSF levels of total alpha-synuclein, with lower levels of proteostasis proteins related to lower levels of total alpha-synuclein. (4) These findings could be confirmed longitudinally. PD patients with low CSF profiles of proteostasis proteins showed lower CSF levels of alpha-synuclein longitudinally compared with PD patients with a normal proteostasis profile. Conclusion CSF proteins associated with neurotransmitter secretion, synaptic plasticity, and endolysosomal autophagy might serve as biomarkers related to alpha-synuclein proteostasis in PD and DLB. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Lindholm, Beata, et al.
(författare)
-
Cognitive and psychiatric symptoms are associated with walking difficulties in mild Parkinson’s disease
- 2020
-
Ingår i: - : Wiley. ; , s. 549-549
-
Konferensbidrag (refereegranskat)abstract
- Objective: To investigate the association of different aspects of cognitive impairment, depression and anxiety with walking difficulties in daily life in persons with mild PD.Background: Walking difficulties in daily life are common among persons with Parkinson’s disease (PD) and may cause falls and near falls, limitations in activity, restrictions in participation and decrease in quality of life. Motor symptoms are often cited as a major reason for these difficulties while the association with cognitive and psychiatric symptoms is still poorly explored.Methods: The study included cross-sectional data from 73 persons with PD that visited a neurology outpatient clinic during 2012-2017. Mean (SD) age was 69 (8.9) years, mean (SD) disease duration was 8 (4.3) years and mean (SD) “on” phase motor symptoms (Unified PD Rating Scale, UPDRS, part III) and cognition (Mini Mental State Examination, MMSE) were 16.4 (9.9) and 27.3 (2.6), respectively. Walking difficulties in daily life (the dependent variable) was investigated with the generic Walk-12 (Walk-12G). Multiple linear regression analysis (controlling for age and motor symptoms) included the following independent variables: cognition (MMSE), memory (Alzheimer's Disease Assessment Scale, ADAS, cognitive subscale), cognitive perception speed (A Quick Test of Cognitive Speed, AQT, part I-III) frontal lobe/executive impairment (Frontal Assessment Battery, FAB) and depression and anxiety (Hospital Anxiety and Depression Scale, HADS). Results: The median Walk-12G scores was 11.5 (q1-q3, 5.5−25.5). Four significant independent variables were identified explaining 15.5% of the variance in the Walk-12G score. The factor with the strongest association with walking difficulties in daily life was cognitive perception speed (AQT part I) (explaining 4.9%) closed followed by anxiety (4.9%), cognitive perception speed (AQT part II) (3%) and frontal lobe/executive impairment (2.7%). Conclusion: Cognitive and psychiatric symptoms are associated with walking difficulties in persons with mild PD. Targeting cognitive perception speed, anxiety and frontal lobe/executive impairments in PD rehabilitation may help improve walking ability in daily life.
|
|
| 48. |
|
|
| 49. |
- Lindholm, Beata, et al.
(författare)
-
Does fatigue in Parkinson’s disease impact one’s physical function in daily live?
- 2023
-
Ingår i: Movement Disorders. - 0885-3185. ; 38:Suppl 1, s. 824-824
-
Konferensbidrag (refereegranskat)abstract
- Objective: To investigate fatigue at baseline and 3.5 years later and its association with balance and gait over time.Background: In Parkinson’s disease (PD), fatigue is considered one of the most common and disabling nonmotor symptoms that may persist or even worsen over time. Fatigue in generally has been described as a significantly diminished energy level or an increased perception of effort disproportionate to attempted activities. Fatigue has been associated to several nonmotor symptoms (e.g., depression, apathy, anxiety, sleep disturbances) and negatively impact quality of life in cross-sectional PD-studies. However, few studies have investigated fatigue over time and its association with other physical symptoms.Method: A prospective cohort of 70 persons with mild to moderate PD was assessed at baseline and 3.5 years later. Mean (SD) age and PD duration at baseline were 66 (8.9) and 4 (4.0) years, respectively and median (q1-q3) “on” phase motor symptoms (Unified PD Rating Scale, UPDRS, part III) were 11 (7-18). Fatigue was investigated with The Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F, higher=better). Multiple linear regression analysis was performed with FACIT-F scores at baseline as dependent variable and a battery of clinical balance and gait tests targeting functional, reactive, and dynamic balance (Bergs Balance Scale vs Nutt Retropulsion Test vs Tandem gait, respectively), comfortable and fast gait speed and functional mobility (Timed up and go, TUG) as independent variables. The results were controlled for age and motor symptoms.Results: The median (q1-q3) FACIT-F scores at baseline (39 (30-36)) were significantly higher than corresponding value 3.5 years later (33.5 (22.5-41)). Significant association was found between FACIT-F scores at baseline and time needed to perform TUG 3.5 years later (B (95% CI); -0,568 (-0,925, -0.211), P=0.002)). These results suggest more than half a second longer time to perform the TUG for every point/score on the FACIT-F.Conclusion: Fatigue in people with PD seem to increase substantially over a relatively short time of 3.5 years. Fatigue also impacts functional mobility incorporating components of balance and gait ability in PD (gait speed, turning and sit-to-stand transfers). More longitudinal studies are needed to investigate long-term impact of fatigue on physical function in daily live.
|
|
| 50. |
- Markaki, I., et al.
(författare)
-
Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson’s Disease
- 2020
-
Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cognitive impairment is common in patients with PD. Core markers of Alzheimer’s dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date. Objectives: The aim of this study was to investigate CSF markers associated with cognition in early PD. Methods: A high-throughput suspension bead array examined 216 proteins in CSF of 74 PD patients in the AETIONOMY project. Cognitive function was assessed with Repeatable Battery for the Assessment of the Neuropsychological Status, Montreal Cognitive Assessment, and Mini-Mental State Examination. Results: Of 69 patients with complete data, 34 had high (≥90) and 35 had low Repeatable Battery for the Assessment of the Neuropsychological Status total score (<90). Of 14 proteins in CSF that differed in levels between groups, increased kininogen-1, validated with several antibodies, was independently associated with lower Repeatable Battery for the Assessment of the Neuropsychological Status and Montreal Cognitive Assessment scores after adjustment for confounders. Conclusions: Kininogen-1 levels in CSF may serve as a marker of cognitive impairment in PD.
|
|
