| 1. |
- Hagell, Peter, et al.
(författare)
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Measurement properties of the SF-12 Health Survey in Parkinson's disease
- 2011
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 1:2, s. 185-196
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Hagell, Peter, et al.
(författare)
-
Measurement Properties of the SF-12 Health Survey in Parkinson's Disease
- 2011
-
Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-718X .- 1877-7171. ; 1:2, s. 185-196
-
Tidskriftsartikel (refereegranskat)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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| 3. |
- Lindgren, Hanna S., et al.
(författare)
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Putaminal Upregulation of FosB/ΔFosB-Like Immunoreactivity in Parkinson's Disease Patients with Dyskinesia
- 2011
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 1:4, s. 347-357
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Sjödahl Hammarlund, Catharina, et al.
(författare)
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The significance of walking from the perspective of people with Parkinson's disease
- 2014
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 4:4, s. 657-663
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is associated with progressive mobility and walking difficulties. Although these aspects have been found to be central from a patient perspective, the perceived significance of walking is less well understood. Objective: To explore the significance of walking as perceived and experienced by individuals with PD. Methods: Eleven persons with PD (seven men; median age, 71 years; median PD duration, 7 years) participated. Data were collected through semi-structured interviews, which were recorded and transcribed verbatim. Data were qualitatively analysed by systematic text condensation. Results: The ability to walk had a complex and multifaceted impact on the participants, including physical, psychological and emotional aspects as well as on the ability to be active in daily life and to participate in society. The central role of coping strategies was prominent in filtering emotional reactions to physical changes, and when managing the activities and participation in everyday situations. The sense of unpredictability, uncertainty and loss of control were underlying phenomena in all categories. Furthermore, inability to manage walking difficulties had a negative impact on the participants' self-concept. Conclusions: The central meaning of being able to walk appears to be intimately linked to an individual's social identity, emotional well-being and integrity. Consequently, being able to walk independently was a prerequisite to an autonomous life and participation in society. This implies that rehabilitation and other mobility interventions also need to consider individual emotional, psychological, and social implications, and to facilitate appropriate compensatory and coping strategies.
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| 5. |
- Skorpil, Mikael, et al.
(författare)
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MRI diffusion in Parkinson's disease : using the technique's inherent directional information to study the olfactory bulb and substantia nigra
- 2012
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Ingår i: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 2:2, s. 171-180
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Tidskriftsartikel (refereegranskat)abstract
- Pathological studies have shown that Parkinson's disease (PD) at early stages affects the olfactory bulb (OB) followed by an involvement of substantia nigra (SN) and other brain regions. Emerging imaging methodologies detect alterations in certain brain regions of living PD patients, which may support proper diagnosis and monitor disease progression. Here we used a novel approach of diffusion tensor imaging (DTI), taking advantage of the technique's inherent diffusion directional information, for region of interest (ROI) placement and diffusion measurements in the OB and SN. 16 healthy individuals and 18 early-moderate patients with PD, supported by reduced ¹²³I-Ioflupane putaminal binding, were examined with two identical DTI series. Olfaction was assessed with the 40-item UPSIT and Parkinsonian severity with UPDRS and Hoehn&Yahr. DTI measurements showed reduced fractional anisotropy (FA) for SN in the PD group in both DTI series. In OBs there was reduced FA in the PD group in the first series, but not in the second. As OBs are located in an area susceptible to artifacts, the coefficient of variation between the two DTI series was higher than for other brain regions. The UPSIT scores were much lower in the PD group than in healthy individuals. In conclusion, we describe a novel approach for more objective ROI placement in DTI, which enabled us to detect altered diffusion in the SN and OBs in PD. These data provides further support that diffusion MRI can be of high clinical utility as a biomarker to facilitate diagnosis and follow disease progression in PD.
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| 6. |
- Trupp, Miles, et al.
(författare)
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Metabolite and peptide levels in plasma and CSF differentiating healthy controls from patients with newly diagnosed Parkinson's disease
- 2014
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Ingår i: Journal of Parkinson's Disease. - : Taylor & Francis. - 1877-7171 .- 1877-718X. ; 4:3, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a progressive, multi-focal neurodegenerative disease for which there is no effective disease modifying treatment. A critical requirement for designing successful clinical trials is the development of robust and reproducible biomarkers identifying PD in preclinical stages. Objective: To investigate the potential for a cluster of biomarkers visualized with multiple analytical platforms to provide a clinically useful tool. Methods: Gas Chromatography-Mass Spectrometry (GC-TOFMS) based metabolomics and immunoassay-based protein/peptide analyses on samples from patients with PD diagnosed in Northern Sweden. Low molecular weight compounds from both plasma and cerebrospinal fluid (CSF) from 20 healthy subjects (controls) and 20 PD patients at the time of diagnosis (baseline) were analyzed. Results: In plasma, we found a significant increase in several amino acids and a decrease in C16-C18 saturated and unsaturated fatty acids in patients as compared to control subjects. We also observed an increase in plasma levels of pyroglutamate and 2-oxoisocaproate (ketoleucine) that may be indicative of increased metabolic stress in patients. In CSF, there was a generally lower level of metabolites in PD as compared to controls, with a specific decrease in 3-hydroxyisovaleric acid, tryptophan and creatinine. Multivariate analysis and modeling of metabolites indicates that while the PD samples can be separated from control samples, the list of detected compounds will need to be expanded in order to define a robust predictive model. CSF biomarker immunoassays of candidate peptide/protein biomarkers revealed a significant decrease in the levels of A beta-38 and A beta-42, and an increase in soluble APP alpha in CSF of patients. Furthermore, these peptides showed significant correlations to each other, and positive correlations to the CSF levels of several 5- and 6-carbon sugars. However, combining these metabolites and proteins/peptides into a single model did not significantly improve the statistical analysis. Conclusions: Together, this metabolomics study has detected significant alterations in plasma and CSF levels of a cluster of amino acids, fatty acids and sugars based on clinical diagnosis and levels of known protein and peptide biomarkers.
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| 9. |
- Decressac, Mickael, et al.
(författare)
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mTOR Inhibition Alleviates L-DOPA-Induced Dyskinesia in Parkinsonian Rats
- 2013
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 3:1, s. 13-17
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Tidskriftsartikel (refereegranskat)abstract
- The development of dyskinesia upon chronic L-DOPA treatment is a major complication for the management of the motor symptoms in Parkinson's disease (PD) patients. Efforts are made to understand the underlying mechanisms and identify targets for the pharmacological alleviation of dyskinesia without affecting the therapeutic effect of L-DOPA. Previous studies have shown that the mTOR pathway is hyperactive in dyskinesia as a consequence of D1 receptor hypersensitivity. We investigated the effect of the FDA-approved mTOR inhibitor Temsirolimus (CCI-779), currently used in the clinic, on the development of LID and on the severity of already established LID in hemi-parkinsonian rats. Systemic delivery of CCI-779 prevented the development of LID and significantly alleviated the severity of dyskinesia in L-DOPA-primed animals. This was associated with a reduced activation of the mTOR pathway in striatal medium spiny neurons. Drugs with mTOR inhibiting activity that are actively developed in cancer research may be of interest for the management of LID in PD patients.
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| 10. |
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