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dc.contributor.authorSzwedo, Aleksandra A
dc.contributor.authorDalen, Ingvild
dc.contributor.authorPedersen, Kenn Freddy
dc.contributor.authorCamacho, Marta
dc.contributor.authorBäckström, David
dc.contributor.authorForsgren, Lars
dc.contributor.authorTzoulis, Charalampos
dc.contributor.authorWinder‐Rhodes, Sophie
dc.contributor.authorHudson, Gavin
dc.contributor.authorLiu, Ganqiang
dc.contributor.authorScherzer, Clemens R
dc.contributor.authorLawson, Rachael A
dc.contributor.authorYarnall, Alison J
dc.contributor.authorWilliams‐Gray, Caroline H
dc.contributor.authorMacleod, Angus D
dc.contributor.authorCounsell, Carl E
dc.contributor.authorTysnes, Ole‐Bjørn
dc.contributor.authorAlves, Guido
dc.contributor.authorMaple‐Grødem, Jodi
dc.date.accessioned2022-02-02T10:20:41Z
dc.date.available2022-02-02T10:20:41Z
dc.date.issued2022-05
dc.date.submitted2021-09-13
dc.identifier.issn0885-3185
dc.identifier.othermds28932
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333555
dc.descriptionFunder: Academy of Medical Sciences; Id: http://dx.doi.org/10.13039/501100000691
dc.descriptionFunder: American Parkinson Disease Association Center for Advanced Parkinson Research
dc.descriptionFunder: BMA Doris Hillier award
dc.descriptionFunder: Bupa Foundation; Id: http://dx.doi.org/10.13039/501100000355
dc.descriptionFunder: Cure Parkinson's Trust
dc.descriptionFunder: Erling‐Persson Foundation
dc.descriptionFunder: European Research Council; Id: http://dx.doi.org/10.13039/501100000781
dc.descriptionFunder: Hjärnfonden; Id: http://dx.doi.org/10.13039/501100003792
dc.descriptionFunder: John and Lucille Van Geest Foundation; Id: http://dx.doi.org/10.13039/501100020410
dc.descriptionFunder: Kempestiftelserna; Id: http://dx.doi.org/10.13039/501100007067
dc.descriptionFunder: Knut och Alice Wallenbergs Stiftelse; Id: http://dx.doi.org/10.13039/501100004063
dc.descriptionFunder: Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse; Id: http://dx.doi.org/10.13039/501100006129
dc.descriptionFunder: Lockhart Parkinson's Disease Research Fund
dc.descriptionFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100007155
dc.descriptionFunder: Medicinska Forskningdet
dc.descriptionFunder: NIHR Newcastle Biomedical Research Unit and Centre
dc.descriptionFunder: NHS Grampian endowments
dc.descriptionFunder: Norwegian Health Association; Id: http://dx.doi.org/10.13039/501100013263
dc.descriptionFunder: Norwegian Parkinson's Research Foundation
dc.descriptionFunder: Patrick Berthoud Trust
dc.descriptionFunder: Rebergs Legacy
dc.descriptionFunder: RS Macdonald Trust
dc.descriptionFunder: SPRING; Id: http://dx.doi.org/10.13039/100001869
dc.descriptionFunder: Swedish Parkinson Foundation
dc.descriptionFunder: Umeå Universitet; Id: http://dx.doi.org/10.13039/501100004885
dc.descriptionFunder: Västerbotten Läns Landsting; Id: http://dx.doi.org/10.13039/501100002960
dc.descriptionFunder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269
dc.description.abstractAbstract: 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
dc.languageen
dc.publisherWiley
dc.subjectRESEARCH ARTICLE
dc.subjectRESEARCH ARTICLES
dc.subjectParkinson's disease
dc.subjectdementia
dc.subjectcognitive decline
dc.subjectAPOE
dc.subjectGBA
dc.title<scp> <i>GBA</i> </scp> and <scp> <i>APOE</i> </scp> Impact Cognitive Decline in Parkinson's Disease: A 10‐Year Population‐Based Study
dc.typeArticle
dc.date.updated2022-02-02T10:20:40Z
prism.publicationNameMovement Disorders
dc.identifier.doi10.17863/CAM.80975
dcterms.dateAccepted2022-01-05
rioxxterms.versionofrecord10.1002/mds.28932
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCamacho, Marta [0000-0002-1490-5703]
dc.contributor.orcidLiu, Ganqiang [0000-0002-1921-9542]
dc.contributor.orcidWilliams‐Gray, Caroline H [0000-0002-2648-9743]
dc.contributor.orcidMacleod, Angus D [0000-0002-6284-4239]
dc.contributor.orcidMaple‐Grødem, Jodi [0000-0001-7142-0078]
dc.identifier.eissn1531-8257
pubs.funder-project-idHelse Vest (911218)
pubs.funder-project-idNational Institutes of Health (NINDS/NIA R01NS115144, U01NS095736, U01NS100603)
pubs.funder-project-idNIHR Cambridge Biomedical Research Centre (BRC‐1215‐20014)
pubs.funder-project-idNorges Forskningsrd (177966, 287842)
pubs.funder-project-idParkinson's UK (G‐0502, G‐0914, G‐1301, G‐1302, G‐1507, J‐0802)
pubs.funder-project-idScottish Chief Scientist Office (CAF/12/05, PCL/17/10)
cam.issuedOnline2022-02-02


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