{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:22:44Z","timestamp":1792801364666,"version":"4.5.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"Importance<\/jats:title>Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event.<\/jats:p><\/jats:sec>Results<\/jats:title>Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n\u2009=\u2009178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, \u22120.77 to 3.80; 1-sided futility test P<\/jats:italic>\u2009=\u2009.006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ISRCTN Identifier: 16108482<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2022.3718","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T15:33:32Z","timestamp":1667230412000},"page":"1232","source":"Crossref","is-referenced-by-count":54,"title":["Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease"],"prefix":"10.1001","volume":"79","author":[{"given":"Kara N.","family":"Stevens","sequence":"first","affiliation":[{"name":"Faculty of Health, University of Plymouth, Plymouth, United Kingdom"},{"name":"Exploristics Ltd, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan","family":"Creanor","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter, Exeter, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Jeffery","sequence":"additional","affiliation":[{"name":"Faculty of Health, University of Plymouth, Plymouth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Whone","sequence":"additional","affiliation":[{"name":"Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Zajicek","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical and Biological Sciences, University of St Andrews, St Andrews, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Foggo","sequence":"additional","affiliation":[{"name":"School of Biological and Marine Sciences, Faculty of Science and Engineering, University of Plymouth, Plymouth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Jones","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter, Exeter, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Chapman","sequence":"additional","affiliation":[{"name":"Faculty of Health, University of Plymouth, Plymouth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cocking","sequence":"additional","affiliation":[{"name":"NIHR BioResource, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonny","family":"Wilks","sequence":"additional","affiliation":[{"name":"MAC Clinical Research, Blackpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doug","family":"Webb","sequence":"additional","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Carroll","sequence":"additional","affiliation":[{"name":"Faculty of Health, University of Plymouth, Plymouth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PD STAT Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemma","family":"Inches","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Underwood","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Frost","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"James","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Schofield","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"James","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"O\u2019Reilly","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Sheridan","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Statton","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Goff","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamlyn","family":"Russell","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Whitcher","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Craw","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Lewis","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Sophia","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Amar","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle","family":"Hernandez","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Pitcher","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Carvey","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Hamlin","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Lyell","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Aubry","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Carey","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Coebergh","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idah","family":"Mojela","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Molloy","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Berceruelo Bergaz","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bintou","family":"Camera","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Campbell","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw","family":"Morris","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinashe","family":"Samakomva","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Schrag","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Fuller","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjum","family":"Misbahuddin","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Parker","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Visentin","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Gallehawk","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Rudd","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Singh","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarsha","family":"Wilson","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Creven","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Croucher","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Tluk","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Watts","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Hargreaves","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Johnson","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Worboys","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Worth","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Brooke","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kobylecki","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Parker","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Johnson","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosane","family":"Joseph","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Melville","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Raw","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Birt","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hare","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saifuddin","family":"Shaik","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Alty","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Cosgrove","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Burn","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Green","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"McNichol","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pavese","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Pilkington","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Price","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Walker","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Podlewska","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth","family":"Reddy","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaval","family":"Trivedi","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Bandmann","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie","family":"Clegg","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Cole","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Emery","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaclav","family":"Dostal","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodie","family":"Graham","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Keshet-Price","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godwin","family":"Mamutse","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Miller-Fik","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Wiltshire","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Wright","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Dixon","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abdelhafiz","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Rose","sequence":"additional","affiliation":[{"name":"for the PD STAT Study Group"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"noi220070r1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson pandemic\u2014a call to action.","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol"},{"issue":"4","key":"noi220070r2","doi-asserted-by":"publisher","first-page":"545","DOI":"10.3233\/JPD-171203","article-title":"Simvastatin as a potential disease-modifying therapy for patients with Parkinson\u2019s disease: rationale for clinical trial, and current progress.","volume":"7","author":"Carroll","year":"2017","journal-title":"J Parkinsons Dis"},{"issue":"5-6","key":"noi220070r3","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1159\/000095679","article-title":"Statins of different brain penetrability differentially affect CSF PLTP activity.","volume":"22","author":"Vuletic","year":"2006","journal-title":"Dement Geriatr Cogn Disord"},{"issue":"2","key":"noi220070r4","doi-asserted-by":"publisher","first-page":"307","DOI":"10.3233\/JAD-2010-101179","article-title":"Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death.","volume":"23","author":"Sierra","year":"2011","journal-title":"J Alzheimers Dis"},{"issue":"3","key":"noi220070r5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152564","article-title":"Statin use and the risk of Parkinson\u2019s disease: an updated meta-analysis.","volume":"11","author":"Bai","year":"2016","journal-title":"PLoS One"},{"issue":"5","key":"noi220070r6","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.numecd.2017.03.001","article-title":"Statin use and risk of new-onset diabetes: a meta-analysis of observational studies.","volume":"27","author":"Casula","year":"2017","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"noi220070r7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.bbr.2016.04.046","article-title":"Statin use and risk of Parkinson\u2019s disease: a meta-analysis.","volume":"309","author":"Sheng","year":"2016","journal-title":"Behav Brain Res"},{"issue":"10","key":"noi220070r8","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-029740","article-title":"Simvastatin as a neuroprotective treatment for Parkinson\u2019s disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study.","volume":"9","author":"Carroll","year":"2019","journal-title":"BMJ Open"},{"issue":"6","key":"noi220070r9","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1097\/01.WNF.0000232277.68501.08","article-title":"End-of-dose wearing off in Parkinson disease: a 9-question survey assessment.","volume":"29","author":"Stacy","year":"2006","journal-title":"Clin Neuropharmacol"},{"issue":"15","key":"noi220070r10","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/mds.22340","article-title":"Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results.","volume":"23","author":"Goetz","year":"2008","journal-title":"Mov Disord"},{"issue":"5","key":"noi220070r11","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1212\/01.wnl.0000201251.33253.fb","article-title":"Optimizing the ongoing search for new treatments for Parkinson disease: using futility designs.","volume":"66","author":"Tilley","year":"2006","journal-title":"Neurology"},{"issue":"1","key":"noi220070r12","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1001\/archneurol.2009.295","article-title":"The clinically important difference on the Unified Parkinson\u2019s Disease Rating Scale.","volume":"67","author":"Shulman","year":"2010","journal-title":"Arch Neurol"},{"issue":"6","key":"noi220070r13","doi-asserted-by":"publisher","first-page":"2730","DOI":"10.1172\/JCI68295","article-title":"Exenatide and the treatment of patients with Parkinson\u2019s disease.","volume":"123","author":"Aviles-Olmos","year":"2013","journal-title":"J Clin Invest"},{"issue":"3","key":"noi220070r15","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1159\/000444021","article-title":"Age, gender, comorbidity, and the MDS-UPDRS: results from a population-based study.","volume":"46","author":"Keezer","year":"2016","journal-title":"Neuroepidemiology"},{"issue":"4","key":"noi220070r16","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1002\/mdc3.2017.4.issue-4","article-title":"Differences in MDS-UPDRS scores based on Hoehn and Yahr stage and disease duration.","volume":"4","author":"Skorvanek","year":"2017","journal-title":"Mov Disord Clin Pract"},{"issue":"9936","key":"noi220070r18","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1016\/S0140-6736(13)62242-4","article-title":"Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial.","volume":"383","author":"Chataway","year":"2014","journal-title":"Lancet"},{"issue":"12","key":"noi220070r19","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.parkreldis.2015.10.006","article-title":"Minimal clinically important difference on the Motor Examination part of MDS-UPDRS.","volume":"21","author":"Horv\u00e1th","year":"2015","journal-title":"Parkinsonism Relat Disord"},{"issue":"6","key":"noi220070r20","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1111\/ane.12796","article-title":"Gender differences in Parkinson\u2019s disease: a clinical perspective.","volume":"136","author":"Georgiev","year":"2017","journal-title":"Acta Neurol Scand"},{"issue":"8","key":"noi220070r22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022854","article-title":"Serum cholesterol and the progression of Parkinson\u2019s disease: results from DATATOP.","volume":"6","author":"Huang","year":"2011","journal-title":"PLoS One"},{"issue":"3","key":"noi220070r23","doi-asserted-by":"publisher","first-page":"237","DOI":"10.14336\/AD.2015.1030","article-title":"Higher plasma LDL-cholesterol is associated with preserved executive and fine motor functions in Parkinson\u2019s disease.","volume":"7","author":"Sterling","year":"2016","journal-title":"Aging Dis"},{"key":"noi220070r24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.parkreldis.2016.07.019","article-title":"Challenges in detecting disease modification in Parkinson\u2019s disease clinical trials.","volume":"32","author":"Athauda","year":"2016","journal-title":"Parkinsonism Relat Disord"},{"issue":"2","key":"noi220070r25","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/(ISSN)1531-8249","article-title":"A responsive outcome for Parkinson\u2019s disease neuroprotection futility studies.","volume":"57","author":"Elm","year":"2005","journal-title":"Ann Neurol"},{"issue":"5","key":"noi220070r26","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1002\/mds.v36.5","article-title":"A double-blind, randomized, controlled trial of lovastatin in early-stage Parkinson\u2019s disease.","volume":"36","author":"Lin","year":"2021","journal-title":"Mov Disord"},{"issue":"1","key":"noi220070r27","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/mds.v35.1","article-title":"Understanding the links between cardiovascular disease and Parkinson\u2019s disease.","volume":"35","author":"Potashkin","year":"2020","journal-title":"Mov Disord"},{"issue":"1","key":"noi220070r28","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.tins.2018.09.007","article-title":"Triggers, facilitators, and aggravators: redefining Parkinson\u2019s disease pathogenesis.","volume":"42","author":"Johnson","year":"2019","journal-title":"Trends Neurosci"},{"key":"noi220070r17","first-page":"78","volume-title":"Clinical Trials in Neurology: Design, Conduct, Analysis","author":"Levin","year":"2012"},{"key":"noi220070r14","unstructured":"Stevens? KN. Simvastatin as a neuroprotective treatment for Parkinson\u2019s disease: a double-blind, randomised, placebo controlled futility study in patients of moderate severity). Accessed October 3, 2022. https:\/\/pearl.plymouth.ac.uk\/bitstream\/handle\/10026.1\/16728\/PD%20stat%20SAP%20v2.2%20signed.pdf?sequence=9&isAllowed=y"},{"key":"noi220070r21","unstructured":"Committee for Human Medicinal Products. Points to consider on implications of coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials. Accessed October 1, 2022. https:\/\/www.ema.europa.eu\/documents\/scientific-guideline\/points-consider-implications-coronavirus-disease-covid-19-methodological-aspects-ongoing-clinical_en-0.pdf"}],"container-title":["JAMA Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/articlepdf\/2797508\/jamaneurology_stevens_2022_oi_220070_1670426906.57775.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T16:01:06Z","timestamp":1670860866000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaneurology\/fullarticle\/2797508"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2022,12,1]]},"references-count":28,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaneurol.2022.3718","relation":{},"ISSN":["2168-6149"],"issn-type":[{"value":"2168-6149","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12,1]]}}}