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| 2. |
- Alves, G., et al.
(författare)
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CSF A beta(42) predicts early-onset dementia in Parkinson disease
- 2014
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 82:20, s. 1784-1790
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To test in vivo the proposal from clinicopathologic studies that -amyloid (A) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF A and related measures as early prognostic biomarkers of dementia in an incident PD cohort.Methods:We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of A42, A40, and A38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of A42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.Results:CSF levels of A42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low A42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for A42(ECL) <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for A42(ELISA) <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. A42 reductions tended to precede the onset of PD-MCI that progressed to dementia.Conclusions:These in vivo data support the role of A pathology in the etiology and highlight the potential utility of CSF A42 as an early prognostic biomarker of dementia associated with PD.
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- Pihlstrom, L., et al.
(författare)
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Fine mapping and resequencing of the PARK16 locus in Parkinson's disease
- 2015
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Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 60:7, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- The PARK16 locus, spanning five genes on chromosome 1, was among the first genetic regions to show genome-wide association in Parkinson's disease (PD). Subsequent investigations have found variability in PARK16 top-hits and association patterns across populations, and the implicated genes and mechanisms are currently unclear. In the present study, we aimed to explore the contribution of PARK16 variability to PD risk in a Scandinavian population. We genotyped 17 single-nucleotide polymorphisms in a case-control sample set of 2570 individuals from Norway and Sweden to fine map the locus. Targeted resequencing of the full coding regions of SLC45A3, NUCKS1, RAB7L1, SLC41A1 and PM20D1 was performed in DNA pools from a subset of 387 patient samples. We find evidence for an association with PD for rs1775143 as well as a haplotype located around the 5' region of RAB7L1, implicating variants which are not in high linkage disequilibrium with the strongest signal from a recent large meta-analysis in Caucasians. We also provide suggestive support for epistasis between RAB7L1 and LRRK2 as previously hypothesized by others. Comparing our results with previous work, allelic heterogeneity at PARK16 appears likely, and further studies are warranted to disentangle the complex patterns of association and pinpoint the functionally relevant variants.
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| 4. |
- Pihlstrom, L., et al.
(författare)
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Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease
- 2013
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:6
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Tidskriftsartikel (refereegranskat)abstract
- enome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.
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| 5. |
- Taule, T., et al.
(författare)
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Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS) in Norway: Protocol for validation and a prospective cohort study
- 2019
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Ingår i: Contemporary Clinical Trials Communications. - : Elsevier BV. - 2451-8654. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- In amyotrophic lateral sclerosis (ALS) cognitive impairment may occur. This could detrimentally influence communication between patient and health-care professionals and make clinical assessment difficult. Given the short life expectancy after diagnosis, it is crucial to accurately identify ALS patients early. Although suitable cognitive screening tools for patients with ALS are available, they have not been evaluated in a Norwegian population. Interpretation of scores for available tests and practical application of scoring is also not well established. The protocol described here involves two related studies that aim to improve the quality of ALS clinical testing instruments used in the Norwegian population. The first is a validation study that evaluates the psychometric properties of the ECAS-Norwegian. The second is a prospective cohort study that evaluates the ECAS-Norwegian as a tool to predict early changes in ability to work, drive a car and the need for advanced therapy. Study 1 is a multicenter study using international quality criteria. Patients with ALS, healthy control subjects, and control subjects with dementia will be included. Primary outcome is ECAS-Norwegian scores. In study 2, patients with ALS will be included. ECAS-Norwegian compared to Clinical Dementia Rating score and Montreal Cognitive Assessment scores will be used as a prognostic tool for working, driving, and initiating advanced life-prolonging therapy. Before clinical implementation, the ECAS-Norwegian needs to be evaluated and validated. Successful validation and implementation of the ECAS-Norwegian may provide early identification of cognitive impairment in ALS, leading to more proactive, individualized treatment.
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| 6. |
- Taule, T., et al.
(författare)
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Norwegian version of the Edinburgh cognitive and behavioural ALS screen: Construct validity, internal consistency, inter-rater, and test-retest reliability
- 2023
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Ingår i: Plos One. - 1932-6203. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundResearch collaboration highlight a need for validated tests in other languages than English. Translation and culture adjustments may threaten essential features of the original instrument. ObjectiveTo assess the internal consistency, inter-rater and test-retest reliability, and construct validity of the Norwegian version of the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS-N). MethodsPerformance of 71 subjects with ALS, 85 healthy controls (HC) and 6 controls with Alzheimer's disease (AD) were assessed with the ECAS-N. Test-retest interval was four months. Internal consistency was evaluated using Cronbach's alpha; reliability was assessed using intraclass correlation coefficient (ICC), Cohen's kappa, and Bland Altman plot. Five hypothesis, including the Montreal Cognitive Assessment (MoCA) screen, was evaluated for construct validity. ResultsECAS-N total score produced a Cronbach's alpha of 0.65, had excellent inter-rater reliability (ICC = 0.99) and acceptable test-retest reliability (ICC = 0.73). Construct validity analysis suggested valid use of the ECAS-N to distinguish people with ALS-specific cognitive impairment from HC (p = 0.001) and those with AD (p = 0.002). The MoCA and ECAS-N were moderately correlated (r = 0.53). ConclusionThe ECAS-N has potential to be used by different testers in clinical practice and research to screen patients with ALS who speak Norwegian and for documenting cognitive impairment over time.
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| 7. |
- Taule, T., et al.
(författare)
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Translation, cultural adaptation, and validation of a screening test for cognitive and behavioural changes in amyotrophic lateral sclerosis
- 2022
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 44:23, s. 7069-7077
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To describe challenges of translating and culturally adapting the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen into Norwegian (ECAS-N), evaluate its content validity; provide age- and education-balanced norms for verbal fluency and cut-off values for abnormal performance. Materials and methods Translation to Norwegian and back-translation to English complied with standard methods. Patients and ALS experts evaluated the relevance, comprehensiveness and comprehensibility of the translated ECAS (ECAS-N). Content validity indexes at the item level (I-CVI), scale level (S-CVI) and inter-rater agreement were calculated. Performance of controls determined norms for written and spoken verbal fluency (n = 559) and cut-off scores for abnormal performance (n = 85). Results High levels of content validity was achieved for all items of the ECAS-N, I-CVI, S-CVI and inter-rater agreement was 87.5%. Age- and education-balanced norms for written and spoken verbal fluency were produced. Cut-off scores of abnormal performance were slightly lower than the original ECAS. Conclusions The ECAS-N holds promise for detecting cognitive and behavioural impairment in Norwegian patients with ALS. Cut-off scores are situational and could slightly vary between different cultures. The ECAS-N can be used in international research, but researchers should be aware of the differences between the tests applied in the studies.
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