| 1. |
- Bäckström, David, et al.
(författare)
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Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study
- 2018
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Ingår i: Neurology. - : Wolters Kluwer. - 1526-632X .- 0028-3878. ; 91:22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease. METHODS: One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality. RESULTS: The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival. CONCLUSION: Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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| 2. |
- Bäckström, David, et al.
(författare)
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PITX3 genotype and risk of dementia in Parkinson's disease : A population-based study
- 2017
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Ingår i: Journal of the Neurological Sciences. - : ELSEVIER SCIENCE BV. - 0022-510X .- 1878-5883. ; 381, s. 278-284
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Tidskriftsartikel (refereegranskat)abstract
- Dementia is a devastating manifestation of Parkinson's disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11 years with extensive investigations, including neuropsychology and DAT-imaging with I-123 FP-CIT. The primary outcome was the incidence of PD dementia (PDD), diagnosed according to published criteria, studied by the Kaplan-Meier method and Cox proportional hazards. Performance in individual cognitive domains, the incidence of visual hallucinations, disease progression and striatal DAT uptake on imaging was also investigated. PD patients carrying the PITX3 C allele had an increased risk of developing PDD (hazard ratio: 2.87, 95% CI: 1.42-5.81, p = 0.003), compared to the PD patients homozygous for the T-allele. Furthermore, the PITX3 C allele carriers with PD had a poorer cognitive performance in the visuospatial domain (p < 0.001) and a higher incidence of visual hallucinations. A trend towards a lower striatal DAT uptake in the PITX3 C allele carriers was suggested, but could not be confirmed. Our results show that a common polymorphism in the PITX3 gene affects the risk of developing PDD and visuospatial dysfunction in idiopathic PD. If validated, these findings can provide new insights into the neurobiology and genetics of non-motor symptoms in PD.
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| 3. |
- Jakobson Mo, Susanna, 1968-, et al.
(författare)
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Accuracy of Visual Assessment of Dopamine Transporter Imaging in Early Parkinsonism
- 2015
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Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 2:1, s. 17-23
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine transporter (DaT) imaging may be supportive in the initial clinical diagnostic workup in patients with suspected parkinsonian diseases, given that the method has the potential to detect dopaminergic degeneration. We investigated the diagnostic accuracy of visual assessment of the initial DaT single-photon emission CT (DaT-SPECT) with 123I-FP-CIT in a large group of early-stage parkinsonian patients. After inclusion in a long-term multidisciplinary population-based prospective study, a baseline DaT-SPECT was done in 171 incidental, L-dopa-naïve, parkinsonian patients (102 men and 69 women) and 37 healthy controls (19 men and 18 women). The results of the DaT-SPECTs were linked to criteria-based clinical diagnoses, which were set after a mean follow-up of 4.6 (±1.7) years. The outcome of the visual assessment was also compared with that of a semiquantitative evaluation method using regions of interest to measure uptake ratios in the caudate and putamen. We found that visual assessment of DaT-SPECT in clinically diagnosed incidental Parkinson's disease patients had a sensitivity of 94% and a specificity of 92%, rendering a positive likelihood ratio of 11.75 and a negative likelihood ratio of 0.07. The proportion of false positives was 1.4% and false negatives 4.8% at baseline. These figures were comparable to those of the semiquantitative method. This study demonstrates that visual interpretation of presynaptic dopamine imaging with 123I-FP-CIT offers reliable support in the diagnostic procedure of early parkinsonian diseases.
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| 4. |
- Jakobson Mo, Susanna, et al.
(författare)
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Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT – a clinical comparison
- 2018
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Ingår i: EJNMMI Research. - : Springer. - 2191-219X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [18F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BPND) quantification and specific uptake value ratios (SUVR).Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BPND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BPND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.
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| 5. |
- Jakobson Mo, Susanna, et al.
(författare)
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Long-term dopamine transporter imaging in Parkinson's disease treated with zona incerta stimulation
- 2016
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Ingår i: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 37:5, s. 499-508
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The caudal zona incerta (cZI) is a promising, clinically beneficial target for deep brain stimulation (DBS) in Parkinson’s disease (PD). To assess whether DBS of the cZI affects the rate of dopamine terminal dysfunction, PD patients with and without DBS were followed prospectively with 123I FP-Cit single photon emission tomography from the first diagnosis and up to 8 years.Methods: Six patients underwent DBS of the cZI during the survey period. Twenty-two PD patients only on pharmacotherapy served as controls. 123I FP-Cit and clinical assessment were performed at baseline and after 1, 3 and 5 years in all patients. Ten patients also underwent a 123I FP-Cit after 8 years. Image data were evaluated semiquantitatively. Mixed-model analysis was used to assess the relative change in 123I FP-Cit uptake and comparison between surgically and conservatively treated PD patients.Results: The relative decrease in 123I FP-Cit uptake was more pronounced in DBS-treated patients than in controls in the more affected caudate (P=0.037) and putamen (P=0.013). The annual decrease rates were higher in the less affected than the more affected putamen, and were slightly greater in DBS-treated patients (4.8%, 95%confidence interval: 8.5–2.2%) than in controls (4.0%, 95% confidence interval: 5.1–3.1%).Conclusion: This long-term prospective study confirms that the underlying dopaminergic dysfunction continues despite clinical improvement in PD patients with DBS of the cZI. A slightly faster rate of decrease in 123I FP-Cit uptake in these patients compared with conservatively treated PD patients may reflect a more aggressive form of PD.
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| 6. |
- Lenfeldt, Niklas, et al.
(författare)
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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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Ingår i: Journal of Parkinson's Disease. - 1877-7171 .- 1877-718X. ; 7:1, s. 129-142
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Tidskriftsartikel (refereegranskat)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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| 7. |
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| 8. |
- Lizana, Helena, et al.
(författare)
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Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand 18F-FE-PE2I in Human Subjects
- 2018
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 59:8, s. 1275-1280
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Tidskriftsartikel (refereegranskat)abstract
- F-18-(E)-N-(3-iodoprop-2-enyl)-2 beta-carbofluoroethoxy-3 beta-(4'-methylphenyl) nortropane (F-18-FE-PE2I) was recently developed and has shown adequate affinity and high selectivity for the dopamine transporter (DAT). Previous studies have shown promising results for F-18-FE-PE2I as a suitable radioligand for DAT imaging. In this study, we investigated the whole-body biodistribution and dosimetry of F-18-FE-PE2I in healthy volunteers to support its utility as a suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were performed immediately after injection followed by 4 whole-body PET/CT scans between 0.5 and 6 h after injection. Blood samples were drawn in connection with the whole-body scans, and all urine was collected until 6 h after injection. Volumes of interest were delineated around 17 organs on all images, and the areas under the time-activity curves were calculated to obtain the total number of decays in the organs. The absorbed doses to organs and the effective dose were calculated using the software IDAC. Results: The highest activity concentration was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after injection. At later time points, the highest concentration was seen in the gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the highest absorbed dose (119 mu Gy/MBq), followed by the liver (46 mu Gy/MBq). The effective dose was 23 mu Sv/MBq (range, 19-28 mu Sv/MBq), resulting in an effective dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The effective dose is within the same order of magnitude as other commonly used PET imaging agents as well as DAT agents. The reasonable effective dose, together with the previously reported favorable characteristics for DAT imaging and quantification, indicates that F-18-FE-PE2I is a suitable radioligand for DAT imaging.
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