| 11. |
- 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.
|
|
| 12. |
- Percetti, M., et al.
(författare)
-
TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study
- 2022
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:9, s. 1938-1943
-
Tidskriftsartikel (refereegranskat)abstract
- Background Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK. Objectives The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO). Methods Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed. Results Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism. Conclusions We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. (c) 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Szwedo, Aleksandra A, et al.
(författare)
-
GBA and APOE impact cognitive decline in Parkinson's disease : A 10-year population-based study
- 2022
-
Ingår i: Movement Disorders. - : John Wiley & Sons. - 0885-3185 .- 1531-8257. ; 37:5, s. 1016-1027
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Common genetic variance in apolipoprotein E (APOE), β-glucocerebrosidase (GBA), microtubule-associated protein tau (MAPT), and α-synuclein (SNCA) has been linked to cognitive decline in Parkinson's disease (PD), although studies have yielded mixed results.OBJECTIVES: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non-selective, population-based cohorts of newly diagnosed PD patients.METHODS: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE-ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini-Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini-Hochberg corrections.RESULTS: Carriers of APOE-ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE-ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non-carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219.CONCLUSIONS: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
| 16. |
|
|
| 17. |
- Thomas, A. J., et al.
(författare)
-
A Longitudinal Study of Plasma pTau181 in Mild Cognitive Impairment with Lewy Bodies and Alzheimer's Disease
- 2022
-
Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:7, s. 1495-1504
-
Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimer's disease (AD) co-pathology is common in dementia with Lewy bodies and is associated with increased decline. Plasma pTau181 is a blood-based biomarker that can detect AD co-pathology. Objectives We investigated whether pTau181 was associated with cognitive decline in mild cognitive impairment with Lewy bodies (MCI-LB) and MCI with AD (MCI-AD). Methods We assessed plasma pTau181 using a single-molecule array (Simoa) immunoassay at baseline and follow-up in a longitudinal cohort of MCI-LB, MCI-AD, and controls. Results One hundred forty-six subjects (56 probable MCI-LB, 22 possible MCI-LB, 44 MCI-AD, and 24 controls) were reviewed for up to 5.7 years. Probable MCI-LB had significantly higher pTau181 (22.2% mean increase) compared with controls and significantly lower (24.4% mean decrease) levels compared with MCI-AD. Receiver operating characteristic analyses of pTau181 in discriminating probable MCI-LB from controls showed an area under the curve (AUC) of 0.68 (83% specificity, 57% sensitivity); for discriminating MCI-AD from healthy controls, AUC was 0.8 (83.3% specificity, 72.7% sensitivity). pTau181 concentration was less useful in discriminating between probable MCI-LB and MCI-AD: AUC of 0.64 (71.4% specificity, 52.3% sensitivity). There was an association between pTau181 and cognitive decline in MCI-AD but not in MCI-LB. In a subset with repeat samples there was a nonsignificant 3% increase per follow-up year in plasma pTau181. The rate of change in pTau181 was not significantly different in different diagnostic subgroups. Conclusions pTau181 was not associated with an increased decline assessed using either baseline or repeat pTau181. pTau181 partially discriminated probable MCI-LB from controls and MCI-AD from controls but was not useful in distinguishing probable MCI-LB from MCI-AD.
|
|
| 18. |
|
|
