{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:44:29Z","timestamp":1790775869471,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23NS0099441\u2010O1A"],"award-info":[{"award-number":["K23NS0099441\u2010O1A"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010173","name":"Smart Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010173","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The penetrance of leucine rich repeat kinase 2 (<jats:italic>LRRK2<\/jats:italic>) mutations is incomplete and may be influenced by environmental and\/or other genetic factors. Nonsteroidal anti\u2010inflammatory drugs (NSAIDs) are known to reduce inflammation and may lower Parkinson's disease (PD) risk, but their role in <jats:italic>LRRK2<\/jats:italic>\u2010associated PD is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective of this study is to evaluate the association of regular NSAID use and <jats:italic>LRRK2<\/jats:italic>\u2010associated PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Symptomatic (\"LRRK2\u2010PD\") and asymptomatic (\"LRRK2\u2010non\u2010PD\") participants with <jats:italic>LRRK2<\/jats:italic> G2019S, R1441X, or I2020T variants (definitely pathogenic variant carriers) or G2385R or R1628P variants (risk variant carriers) from 2 international cohorts provided information on regular ibuprofen and\/or aspirin use (\u22652 pills\/week for \u22656 months) prior to the index date (diagnosis date for PD, interview date for non\u2010PD). Multivariate logistic regression was used to evaluate the relationship between regular NSAID use and PD for any NSAID, separately for ibuprofen and aspirin in all carriers and separately in pathogenic and risk variant groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 259 LRRK2\u2010PD and 318 LRRK2\u2010non\u2010PD participants were enrolled. Regular NSAID use was associated with reduced odds of PD in the overall cohort (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.21\u20130.57) and in both pathogenic and risk variant carriers (OR<jats:sub>Pathogenic<\/jats:sub>, 0.38; 95% CI, 0.21\u20130.67 and OR<jats:sub>RiskVariant<\/jats:sub>, 0.19; 95% CI, 0.04\u20130.99). Similar associations were observed for ibuprofen and aspirin separately (OR<jats:sub>Ibuprofen<\/jats:sub>, 0.19; 95% CI, 0.07\u20130.50 and OR<jats:sub>Aspirin<\/jats:sub>, 0.51; 95% CI, 0.28\u20130.91).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Regular NSAID use may be associated with reduced penetrance in <jats:italic>LRRK2<\/jats:italic>\u2010associated PD. The LRRK2 protein is involved in inflammatory pathways and appears to be modulated by regular anti\u2010inflammatory use. Longitudinal observational and interventional studies of NSAID exposure and LRRK2\u2010PD are needed to confirm this association. \u00a9 2020 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28189","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T06:14:30Z","timestamp":1594707270000},"page":"1755-1764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Nonsteroidal <scp>Anti\u2010inflammatory<\/scp> Use and <scp><i>LRRK2<\/i><\/scp> Parkinson's Disease Penetrance"],"prefix":"10.1002","volume":"35","author":[{"given":"Marta","family":"San Luciano","sequence":"first","affiliation":[{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"},{"name":"Department of Neurology San Francisco Veterans Affairs Medical Center  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Marras","sequence":"additional","affiliation":[{"name":"The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Centre  Toronto Ontario Canada"},{"name":"Department of Neurology Toronto Western Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel M.","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco  San Francisco California USA"},{"name":"Department of Medicine University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Lang","sequence":"additional","affiliation":[{"name":"The Edmond J. 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William","family":"Langston","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"},{"name":"Department of Neurology Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Brice","sequence":"additional","affiliation":[{"name":"Sorbonne Universites, UPMC Universite Paris 6 UMR_S 1127, INSERM U 1127 CNRS UMR 7225, Institut du Cerveau et de la Moelle epiniere, ICM  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Christophe","family":"Corvol","sequence":"additional","affiliation":[{"name":"Sorbonne Universites, UPMC Universite Paris 6 UMR_S 1127, INSERM U 1127 CNRS UMR 7225, Institut du Cerveau et de la Moelle epiniere, ICM  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Goldwurm","sequence":"additional","affiliation":[{"name":"Parkinson Institute  ASST G.Pini\u2010CTO Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of Luebeck  Luebeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Brockman","sequence":"additional","affiliation":[{"name":"School of Psychiatry and Clinical Neurosciences University of Western Australia and Fremantle Hospital  Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Berg","sequence":"additional","affiliation":[{"name":"Department for Neurodegenerative Diseases, Hertie\u2013Institute for Clinical Brain Research University of Tuebingen  Tuebingen Germany"},{"name":"Department of Neurology Christian\u2010Albrechts\u2010University of Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Brockmann","sequence":"additional","affiliation":[{"name":"Department for Neurodegenerative Diseases, Hertie\u2013Institute for Clinical Brain Research University of Tuebingen  Tuebingen Germany"},{"name":"Department of Neurology Christian\u2010Albrechts\u2010University of Kiel  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim J.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit Instituto de Medicina Molecular  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Tazir","sequence":"additional","affiliation":[{"name":"Service de Neurologie CHU Mustapha  Alger Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George D.","family":"Mellick","sequence":"additional","affiliation":[{"name":"Griffith Institute for Drug Discovery Griffith University  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn M.","family":"Sue","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Kolling Institute, University of Sydney  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Sagamihara National Hospital  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng King","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology Singapore General Hospital  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Bressman","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Saunders\u2010Pullman","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Michael J. 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