Differences in Survival across Monogenic Forms of Parkinson's Disease.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
04
02
2023
received:
13
09
2022
accepted:
07
03
2023
medline:
30
6
2023
pubmed:
12
3
2023
entrez:
11
3
2023
Statut:
ppublish
Résumé
Survival of patients with monogenic Parkinson's disease may depend on the causative genes associated with the disease. In this study, we compare survival of patients with Parkinson's disease according to the presence of SNCA, PRKN, LRRK2, or GBA mutations. Data from the French Parkinson Disease Genetics national multicenter cohort study were used. Patients with sporadic and familial Parkinson's disease were recruited between 1990 and 2021. Patients were genotyped for the presence of mutations in the SNCA, PRKN, LRRK2, or GBA genes. Vital status was collected from the National death register for participants born in France. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariable Cox proportional hazards regression. Of the 2,037 patients with Parkinson's disease, 889 had died after a follow-up of up to 30 years. Patients with PRKN (n = 100, HR = 0.41; p = 0.001) and LRRK2 mutations (n = 51, HR = 0.49; p = 0.023) had longer survival than those without any mutation, whereas patients with SNCA (n = 20, HR = 9.88; p < 0.001) or GBA mutations (n = 173, HR = 1.33; p = 0.048) had shorter survival. Survival differs across genetic forms of Parkinson's disease, with higher mortality for patients with SNCA or GBA mutations, and lower mortality for those with PRKN or LRRK2 mutations. Differences in severity and disease progression among monogenic forms of Parkinson's disease likely explain these findings, which has important consequences for genetic counselling and choice of end points for future clinical trials for targeted therapies. ANN NEUROL 2023;94:123-132.
Substances chimiques
Glucosylceramidase
EC 3.2.1.45
Types de publication
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
123-132Investigateurs
Yves Agid
(Y)
Mathieu Anheim
(M)
Michel Borg
(M)
Alexis Brice
(A)
Emmanuel Broussolle
(E)
Jean-Christophe Corvol
(JC)
Philippe Damier
(P)
Luc Defebvre
(L)
Alexandra Dürr
(A)
Franck Durif
(F)
Jean Luc Houeto
(JL)
Paul Krack
(P)
Stephan Klebe
(S)
Suzanne Lesage
(S)
Ebba Lohmann
(E)
Maria Martinez
(M)
Graziella Mangone
(G)
Louise-Laure Mariani
(LL)
Pierre Pollak
(P)
Olivier Rascol
(O)
François Tison
(F)
Christine Tranchant
(C)
Marc Vérin
(M)
François Viallet
(F)
Marie Vidailhet
(M)
Informations de copyright
© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Macleod AD, Taylor KSM, Counsell CE. Mortality in Parkinson's disease: a systematic review and meta-analysis. Mov Disord 2014;29:1615-1622.
Evans JR, Mason SL, Williams-Gray CH, et al. The natural history of treated Parkinson's disease in an incident, community based cohort. J Neurol Neurosurg Psychiatry 2011;82:1112-1118.
Braak H, Rüb U, Jansen Steur ENH, et al. Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology 2005;64:1404-1410.
Selikhova M, Williams DR, Kempster PA, et al. A clinico-pathological study of subtypes in Parkinson's disease. Brain 2009;132:2947-2957.
Greenland JC, Williams-Gray CH, Barker RA. The clinical heterogeneity of Parkinson's disease and its therapeutic implications. Eur J Neurosci 2019;49:328-338.
Reed X, Bandrés-Ciga S, Blauwendraat C, Cookson MR. The role of monogenic genes in idiopathic Parkinson's disease. Neurobiol Dis 2019;124:230-239.
Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 2009;361:1651-1661.
Brockmann K, Srulijes K, Pflederer S, et al. GBA-associated Parkinson's disease: reduced survival and more rapid progression in a prospective longitudinal study. Mov Disord 2015;30:407-411.
Cilia R, Tunesi S, Marotta G, et al. Survival and dementia in GBA-associated Parkinson's disease: the mutation matters. Ann Neurol 2016;80:662-673.
Thaler A, Kozlovski T, Gurevich T, et al. Survival rates among Parkinson's disease patients who carry mutations in the LRRK2 and GBA genes: PD survival with gene mutations. Mov Disord 2018;33:1656-1660.
Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry. juin 1988;51(6):745-52.
Fichier des personnes décédées (Décès). data.gouv.fr [Internet]. [cité 21 juill 2022]. Disponible sur: https://www.data.gouv.fr/en/datasets/fichier-des-personnes-decedees/.
Lesage S, Lunati A, Houot M, et al. Characterization of recessive Parkinson disease in a large multicenter study. Ann Neurol 2020;88:843-850.
Lesage S, Houot M, Mangone G, et al. Genetic and phenotypic basis of autosomal dominant Parkinson's disease in a large multi-center cohort. Front Neurol 2020;11:682.
Lesage S, Anheim M, Condroyer C, et al. Large-scale screening of the Gaucher's disease-related glucocerebrosidase gene in Europeans with Parkinson's disease. Hum Mol Genet 2011;20:202-210.
Zampieri S, Cattarossi S, Bembi B, Dardis A. GBA analysis in next-generation era: pitfalls, challenges, and possible solutions. J Mol Diagn 2017;19:733-741.
Beutler E, Gelbart T, Scott CR. Hematologically important mutations: Gaucher disease. Blood Cells Mol Dis 2005;35:355-364.
Taux de mortalité par sexe et âge [Internet]. Ined - Institut national d'études démographiques. [cité 4 avr 2022]. Disponible sur: https://www.ined.fr/fr/tout-savoir-population/chiffres/france/mortalite-cause-deces/taux-mortalite-sexe-age/.
Lohmann E, Periquet M, Bonifati V, et al. How much phenotypic variation can be attributed to parkin genotype? Ann Neurol 2003;54:176-185.
Chen Z, Li G, Liu J. Autonomic dysfunction in Parkinson's disease: implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis 2020;134:104700.
Planas-Ballvé A, Vilas D. Cognitive impairment in genetic Parkinson's disease. Parkinsons Dis 2021;2021:8610285.
Sun YM, Yu HL, Zhou XY, et al. Disease progression in patients with Parkin-related Parkinson's disease in a longitudinal cohort. Mov Disord 2021;36:442-448.
Schneider SA, Alcalay RN. Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov Disord 2017;32:1504-1523.
Papapetropoulos S, Paschalis C, Ellul J, et al. Survival duration of Parkinson's disease patients living in Greece who carry the G209A ?-synuclein mutation. Mov Disord 2002;17:847-848.
Fuchs J, Nilsson C, Kachergus J, et al. Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology 2007;68:916-922.
Book A, Guella I, Candido T, et al. A meta-analysis of α-synuclein multiplication in Familial Parkinsonism. Front Neurol 2018;9:1021.
Saunders-Pullman R, Mirelman A, Alcalay RN, et al. Progression in the LRRK2-associated Parkinson disease population. JAMA Neurol 2018;75:312-319.
Stoker TB, Camacho M, Winder-Rhodes S, et al. Impact of GBA1 variants on long-term clinical progression and mortality in incident Parkinson's disease. J Neurol Neurosurg Psychiatry 2020;91:695-702.
Liu G, Boot B, Locascio JJ, et al. Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's. Ann Neurol 2016;80:674-685.
Hely MA, Reid WGJ, Adena MA, et al. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord 2008;23:837-844.
Beyer MK, Herlofson K, Arsland D, Larsen JP. Causes of death in a community-based study of Parkinson's disease. Acta Neurol Scand 2001;103:7-11.
Fall PA, Saleh A, Fredrickson M, et al. Survival time, mortality, and cause of death in elderly patients with Parkinson's disease: a 9-year follow-up. Mov Disord 2003;18:1312-1316.
D'Amelio M, Ragonese P, Morgante L, et al. Long-term survival of Parkinson's disease: a population-based study. J Neurol 2006;253:33-37.
Pinter B, Diem-Zangerl A, Wenning GK, et al. Mortality in Parkinson's disease: a 38-year follow-up study. Mov Disord 2015;30:266-269.
Won JH, Byun SJ, Oh BM, et al. Risk and mortality of aspiration pneumonia in Parkinson's disease: a nationwide database study. Sci Rep 2021;11:6597.
De Pablo-Fernandez E, Tur C, Revesz T, et al. Association of Autonomic Dysfunction with Disease Progression and Survival in Parkinson disease. JAMA. Neurology 2017;74:970-976.
Alcalay RN, Kehoe C, Shorr E, et al. Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists. Genet Med 2020;22:574-580.
Schneider SA, Alcalay RN. Precision medicine in Parkinson's disease: emerging treatments for genetic Parkinson's disease. J Neurol 2020;267:860-869.
Li JQ, Tan L, Yu JT. The role of the LRRK2 gene in parkinsonism. Mol Neurodegener 2014;9:47.
Hustad E, Myklebust TÅ, Gulati S, Aasly JO. Increased mortality in young-onset Parkinson's disease. J Mov Disord 2021;14:214-220.
Deelen J, Evans DS, Arking DE, et al. A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nat Commun 2019;10:3669.
Paul KC, Schulz J, Bronstein JM, et al. Association of Polygenic Risk Score with Cognitive Decline and Motor Progression in Parkinson disease. JAMA Neurol 2018;75:360-366.