{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:48:30Z","timestamp":1791280110134,"version":"4.1.0"},"reference-count":99,"publisher":"American Chemical Society (ACS)","issue":"11-12","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":1603,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: The etiology and natural history of Parkinson\u2019s disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years.<\/jats:p>\n                  <jats:p>Objectives: We examined the promise and pitfalls of research on premotor symptoms of PD and developed priorities and strategies to understand their clinical and etiological implications.<\/jats:p>\n                  <jats:p>Methods: This review was based on a workshop, Parkinson\u2019s Disease Premotor Symptom Symposium, held 7\u20138 June 2012 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.<\/jats:p>\n                  <jats:p>Discussion: Research on premotor symptoms of PD may offer an excellent opportunity to characterize high-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of premotor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these premotor symptoms and their relevance to PD pathogenesis are poorly understood.<\/jats:p>\n                  <jats:p>Conclusion: This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple premotor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will further understanding of the biology of these premotor symptoms and test novel etiological hypothesis.<\/jats:p>\n                  <jats:p>Citation: Chen H, Burton EA, Ross GW, Huang X, Savica R, Abbott RD, Ascherio A, Caviness JN, Gao X, Gray KA, Hong JS, Kamel F, Jennings D, Kirshner A, Lawler C, Liu R, Miller GW, Nussbaum R, Peddada SD, Comstock Rick A, Ritz B, Siderowf AD, Tanner CM, Tr\u00f6ster AI, Zhang J. 2013. Research on the premotor symptoms of Parkinson\u2019s Disease: clinical and etiological implications. Environ Health Perspect 121:1245\u20131252;\u2002http:\/\/dx.doi.org\/10.1289\/ehp.1306967<\/jats:p>","DOI":"10.1289\/ehp.1306967","type":"journal-article","created":{"date-parts":[[2013,8,9]],"date-time":"2013-08-09T12:03:26Z","timestamp":1376049806000},"page":"1245-1252","source":"Crossref","is-referenced-by-count":72,"title":["Research on the Premotor Symptoms of Parkinson\u2019s Disease: Clinical and Etiological Implications"],"prefix":"10.1021","volume":"121","author":[{"given":"Honglei","family":"Chen","sequence":"first","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Burton","sequence":"additional","affiliation":[{"name":"Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Webster","family":"Ross","sequence":"additional","affiliation":[{"name":"Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Huang","sequence":"additional","affiliation":[{"name":"Pennsylvania State University\u2013Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Savica","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Abbott","sequence":"additional","affiliation":[{"name":"University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ascherio","sequence":"additional","affiliation":[{"name":"Harvard School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Caviness","sequence":"additional","affiliation":[{"name":"Mayo Clinic Arizona, Scottsdale, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Harvard School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Gray","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jau-Shyong","family":"Hong","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freya","family":"Kamel","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danna","family":"Jennings","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Kirshner","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Lawler","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Miller","sequence":"additional","affiliation":[{"name":"Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Nussbaum","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamal D.","family":"Peddada","sequence":"additional","affiliation":[{"name":"National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Comstock","family":"Rick","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Action Network, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Ritz","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Siderowf","sequence":"additional","affiliation":[{"name":"Avid Radiopharmaceuticals, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Tanner","sequence":"additional","affiliation":[{"name":"The Parkinson Institute, Sunnyvale, California, USA"},{"name":"Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander I.","family":"Tr\u00f6ster","sequence":"additional","affiliation":[{"name":"Barrow Neurological Institute, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2013,8,9]]},"reference":[{"issue":"3","key":"2026080601020549300_micit1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1212\/WNL.57.3.456","article-title":"Frequency of bowel movements and the future risk of Parkinson\u2019s disease.","volume":"57","author":"Abbott","year":"2001","journal-title":"Neurology"},{"issue":"11","key":"2026080601020549300_micit2","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1002\/mds.21560","article-title":"Bowel movement frequency in late-life and incidental Lewy bodies.","volume":"22","author":"Abbott","year":"2007","journal-title":"Mov Disord"},{"issue":"9","key":"2026080601020549300_micit3","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1212\/01.wnl.0000183056.89590.0d","article-title":"Excessive daytime sleepiness and subsequent development of Parkinson disease.","volume":"65","author":"Abbott","year":"2005","journal-title":"Neurology"},{"issue":"1","key":"2026080601020549300_micit4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.expneurol.2007.05.010","article-title":"Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson\u2019s disease.","volume":"207","author":"Anderson","year":"2007","journal-title":"Exp Neurol"},{"issue":"12","key":"2026080601020549300_micit5","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1002\/mds.23878","article-title":"Projected numbers of people with movement disorders in the years 2030 and 2050.","volume":"26","author":"Bach","year":"2011","journal-title":"Mov Disord"},{"issue":"1","key":"2026080601020549300_micit6","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/j.1468-1331.2012.03798.x","article-title":"The PRIPS study: screening battery for subjects at risk for Parkinson\u2019s disease.","volume":"20","author":"Berg","year":"2013","journal-title":"Eur J Neurol"},{"issue":"5","key":"2026080601020549300_micit7","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/mds.24985","article-title":"Defining at-risk populations for Parkinson\u2019s disease: lessons from ongoing studies.","volume":"27","author":"Berg","year":"2012","journal-title":"Mov Disord"},{"issue":"1","key":"2026080601020549300_micit8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/mds.25108","article-title":"Animal models of Parkinson\u2019s disease: limits and relevance to neuroprotection studies.","volume":"28","author":"Bezard","year":"2012","journal-title":"Mov Disord"},{"key":"2026080601020549300_micit9","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/845618","article-title":"Classic and new animal models of Parkinson\u2019s disease.","volume":"845618","author":"Blesa","year":"2012","journal-title":"J Biomed Biotechnol"},{"issue":"5","key":"2026080601020549300_micit10","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.sleep.2010.12.009","article-title":"Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort.","volume":"12","author":"Boeve","year":"2011","journal-title":"Sleep Med"},{"issue":"6","key":"2026080601020549300_micit11","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1212\/01.wnl.0000209264.61035.bb","article-title":"REM sleep behavior disorder: a possible early marker for synucleinopathies.","volume":"66","author":"Boeve","year":"2006","journal-title":"Neurology"},{"issue":"13","key":"2026080601020549300_micit12","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1002\/mds.23230","article-title":"Anxious personality predicts an increased risk of Parkinson\u2019s disease.","volume":"25","author":"Bower","year":"2010","journal-title":"Mov Disord"},{"issue":"2","key":"2026080601020549300_micit13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease.","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol Aging"},{"issue":"4","key":"2026080601020549300_micit14","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1097\/00005537-200404000-00026","article-title":"Prevalence of olfactory dysfunction: the Sk\u00f6vde population-based study.","volume":"114","author":"Br\u00e4merson","year":"2004","journal-title":"Laryngoscope"},{"issue":"5","key":"2026080601020549300_micit15","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/ana.21541","article-title":"A critical evaluation of the Braak staging scheme for Parkinson\u2019s disease.","volume":"64","author":"Burke","year":"2008","journal-title":"Ann Neurol"},{"issue":"30","key":"2026080601020549300_micit16","doi-asserted-by":"crossref","first-page":"8138","DOI":"10.1523\/JNEUROSCI.0319-07.2007","article-title":"Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration.","volume":"27","author":"Caudle","year":"2007","journal-title":"J Neurosci"},{"issue":"7","key":"2026080601020549300_micit17","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1002\/mds.20881","article-title":"Survival of Parkinson\u2019s disease patients in a large prospective cohort of male health professionals.","volume":"21","author":"Chen","year":"2006","journal-title":"Mov Disord"},{"issue":"6","key":"2026080601020549300_micit18","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1212\/WNL.0b013e3181ec7fac","article-title":"REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century.","volume":"75","author":"Claassen","year":"2010","journal-title":"Neurology"},{"issue":"8","key":"2026080601020549300_micit19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nrneurol.2012.126","article-title":"Late-stage Parkinson disease.","volume":"8","author":"Coelho","year":"2012","journal-title":"Nat Rev Neurol"},{"issue":"3","key":"2026080601020549300_micit20","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1001\/archneur.63.3.noc50312","article-title":"Subjective complaints precede Parkinson disease: the Rotterdam study.","volume":"63","author":"de Lau","year":"2006","journal-title":"Arch Neurol"},{"issue":"suppl 1","key":"2026080601020549300_micit21","first-page":"S78","article-title":"Evidence in favor of Braak staging of Parkinson\u2019s disease.","volume":"25","author":"Dickson","year":"2010","journal-title":"Mov Disord"},{"issue":"1","key":"2026080601020549300_micit22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/ana.21327","article-title":"The olfactory vector hypothesis of neurodegenerative disease: Is it viable?","volume":"63","author":"Doty","year":"2008","journal-title":"Ann Neurol"},{"issue":"1","key":"2026080601020549300_micit23","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1055\/s-0028-1124025","article-title":"The olfactory system and its disorders.","volume":"29","author":"Doty","year":"2009","journal-title":"Semin Neurol"},{"issue":"2 pt 1","key":"2026080601020549300_micit24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1288\/00005537-198402000-00004","article-title":"University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic.","volume":"94","author":"Doty","year":"1984","journal-title":"Laryngoscope"},{"issue":"1","key":"2026080601020549300_micit25","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.nbd.2009.06.017","article-title":"Chronic rotenone exposure reproduces Parkinson\u2019s disease gastrointestinal neuropathology.","volume":"36","author":"Drolet","year":"2009","journal-title":"Neurobiol Dis"},{"issue":"2","key":"2026080601020549300_micit26","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.pneurobio.2011.11.003","article-title":"Can Parkinson\u2019s disease pathology be propagated from one neuron to another?","volume":"97","author":"Dunning","year":"2012","journal-title":"Prog Neurobiol"},{"issue":"9","key":"2026080601020549300_micit27","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/mds.23092","article-title":"Depression and the subsequent risk of Parkinson\u2019s disease in the NIH-AARP Diet and Health Study.","volume":"25","author":"Fang","year":"2010","journal-title":"Mov Disord"},{"issue":"pt 5","key":"2026080601020549300_micit28","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1093\/brain\/114.5.2283","article-title":"Ageing and Parkinson\u2019s disease: substantia nigra regional selectivity.","volume":"114","author":"Fearnley","year":"1991","journal-title":"Brain"},{"issue":"suppl 2","key":"2026080601020549300_micit29","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.3949\/ccjm.79.s2a.03","article-title":"Nonmotor complications of Parkinson disease.","volume":"79","author":"Fernandez","year":"2012","journal-title":"Cleve Clin J Med"},{"issue":"42","key":"2026080601020549300_micit30","doi-asserted-by":"crossref","first-page":"9434","DOI":"10.1523\/JNEUROSCI.3080-04.2004","article-title":"Early and progressive sensorimotor anomalies in mice overexpressing wild-type human \u03b1-synuclein.","volume":"24","author":"Fleming","year":"2004","journal-title":"J Neurosci"},{"issue":"2","key":"2026080601020549300_micit31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1460-9568.2008.06346.x","article-title":"Olfactory deficits in mice overexpressing human wildtype \u03b1-synuclein.","volume":"28","author":"Fleming","year":"2008","journal-title":"Eur J Neurosci"},{"issue":"9","key":"2026080601020549300_micit32","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1093\/aje\/kwq478","article-title":"Daytime napping, nighttime sleeping, and Parkinson disease.","volume":"173","author":"Gao","year":"2011","journal-title":"Am J Epidemiol"},{"issue":"5","key":"2026080601020549300_micit33","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/aje\/kwr119","article-title":"A prospective study of bowel movement frequency and risk of Parkinson\u2019s disease.","volume":"174","author":"Gao","year":"2011","journal-title":"Am J Epidemiol"},{"issue":"2","key":"2026080601020549300_micit34","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.brainres.2005.02.036","article-title":"Sleep disturbances in the rotenone animal model of Parkinson disease.","volume":"1042","author":"Garc\u00eda-Garc\u00eda","year":"2005","journal-title":"Brain Res"},{"issue":"suppl 3","key":"2026080601020549300_micit35","doi-asserted-by":"crossref","first-page":"S34","DOI":"10.3949\/ccjm.77.s3.06","article-title":"Neuroscience and heart-brain medicine: the year in review.","volume":"77","author":"Goldstein","year":"2010","journal-title":"Cleve Clin J Med"},{"key":"2026080601020549300_micit36","doi-asserted-by":"publisher","first-page":"94","DOI":"10.3389\/fphys.2011.00094","article-title":"Brain\u2013gut\u2013microbe communication in health and disease.","volume":"2","author":"Grenham","year":"2011","journal-title":"Front Physiol"},{"issue":"6","key":"2026080601020549300_micit37","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1365-2990.2007.00874.x","article-title":"Parkinson\u2019s disease: a dual-hit hypothesis.","volume":"33","author":"Hawkes","year":"2007","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2026080601020549300_micit38","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1749-6632.2009.04365.x","article-title":"Parkinson\u2019s disease: the dual hit theory revisited.","volume":"1170","author":"Hawkes","year":"2009","journal-title":"Ann NY Acad Sci"},{"issue":"2","key":"2026080601020549300_micit39","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.parkreldis.2009.08.007","article-title":"A timeline for Parkinson\u2019s disease.","volume":"16","author":"Hawkes","year":"2010","journal-title":"Parkinsonism Relat Disord"},{"issue":"10","key":"2026080601020549300_micit40","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1177\/000348940111001015","article-title":"Screening of olfactory function with a four-minute odor identification test: reliability, normative data, and investigations in patients with olfactory loss.","volume":"110","author":"Hummel","year":"2001","journal-title":"Ann Otol Rhinol Laryngol"},{"issue":"7","key":"2026080601020549300_micit41","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S1474-4422(06)70476-8","article-title":"Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study.","volume":"5","author":"Iranzo","year":"2006","journal-title":"Lancet Neurol"},{"issue":"11","key":"2026080601020549300_micit42","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1111\/j.1468-1331.2008.02299.x","article-title":"Prospective association between emotional health and clinical evidence of Parkinson\u2019s disease.","volume":"15","author":"Ishihara-Paul","year":"2008","journal-title":"Eur J Neurol"},{"issue":"5","key":"2026080601020549300_micit43","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1523\/JNEUROSCI.5123-11.2012","article-title":"Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice.","volume":"32","author":"Jang","year":"2012","journal-title":"J Neurosci"},{"issue":"33","key":"2026080601020549300_micit44","doi-asserted-by":"crossref","first-page":"14063","DOI":"10.1073\/pnas.0900096106","article-title":"Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration.","volume":"106","author":"Jang","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1\u20132","key":"2026080601020549300_micit45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jns.2011.04.012","article-title":"Synuclein deposition and non-motor symptoms in Parkinson disease.","volume":"310","author":"Jellinger","year":"2011","journal-title":"J Neurol Sci"},{"issue":"1","key":"2026080601020549300_micit46","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.expneurol.2011.08.003","article-title":"Circadian dysfunction in a mouse model of Parkinson\u2019s disease.","volume":"232","author":"Kudo","year":"2011","journal-title":"Exp Neurol"},{"issue":"9","key":"2026080601020549300_micit47","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1093\/hmg\/ddq038","article-title":"Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated \u03b1-synuclein gene mutations precede central nervous system changes.","volume":"19","author":"Kuo","year":"2010","journal-title":"Hum Mol Genet"},{"issue":"4","key":"2026080601020549300_micit48","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00221-008-1268-1","article-title":"MPTP-treated mice: long-lasting loss of nigral TH-ir neurons but not paradoxical sleep alterations.","volume":"186","author":"Laloux","year":"2008","journal-title":"Exp Brain Res"},{"issue":"7","key":"2026080601020549300_micit49","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/jnr.22611","article-title":"Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human \u03b1-synuclein.","volume":"89","author":"Lam","year":"2011","journal-title":"J Neurosci Res"},{"issue":"5","key":"2026080601020549300_micit50","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/mds.23609","article-title":"A critical appraisal of the premotor symptoms of Parkinson\u2019s disease: potential usefulness in early diagnosis and design of neuroprotective trials.","volume":"26","author":"Lang","year":"2011","journal-title":"Mov Disord"},{"issue":"2","key":"2026080601020549300_micit51","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s10620-006-9298-7","article-title":"Etiologic factors of chronic constipation: review of the scientific evidence.","volume":"52","author":"Leung","year":"2007","journal-title":"Dig Dis Sci"},{"issue":"4","key":"2026080601020549300_micit52","doi-asserted-by":"crossref","first-page":"436","DOI":"10.3122\/jabfm.2011.04.100272","article-title":"Chronic constipation: an evidence-based review.","volume":"24","author":"Leung","year":"2011","journal-title":"J Am Board Fam Med"},{"issue":"1","key":"2026080601020549300_micit53","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.sleep.2009.06.008","article-title":"Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK).","volume":"11","author":"Li","year":"2009","journal-title":"Sleep Med"},{"issue":"6109","key":"2026080601020549300_micit54","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological \u03b1-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"issue":"4","key":"2026080601020549300_micit55","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1212\/WNL.0b013e318227042d","article-title":"Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers.","volume":"77","author":"Marras","year":"2011","journal-title":"Neurology"},{"issue":"4","key":"2026080601020549300_micit56","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jpainsymman.2008.04.016","article-title":"A review of the literature on gender and age differences in the prevalence and characteristics of constipation in North America.","volume":"37","author":"McCrea","year":"2009","journal-title":"J Pain Symptom Manage"},{"issue":"3","key":"2026080601020549300_micit57","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.nbd.2011.12.040","article-title":"Animal models of the non-motor features of Parkinson\u2019s disease.","volume":"46","author":"McDowell","year":"2012","journal-title":"Neurobiol Dis"},{"issue":"1","key":"2026080601020549300_micit58","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/ana.22165","article-title":"Gait alterations in healthy carriers of the LRRK2 G2019S mutation.","volume":"69","author":"Mirelman","year":"2011","journal-title":"Ann Neurol"},{"key":"2026080601020549300_micit59","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbt049","article-title":"Meta-analysis of olfactory function in schizophrenia, first-degree family members, and youths at-risk for psychosis.","author":"Moberg","year":"2013","journal-title":"Schizophr Bull"},{"key":"2026080601020549300_micit60","unstructured":"NINDS (National Institute of Neurological Disorders and Stroke).\n          \n          2013. NINDS Common Data Elements: Parkinson\u2019s Disease.Available: http:\/\/www.commondataelements.ninds.nih.gov\/PD.aspx#tab=Data_Standards [accessed 5 August 2013]."},{"issue":"6","key":"2026080601020549300_micit61","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/ana.23687","article-title":"Meta-analysis of early nonmotor features and risk factors for Parkinson disease.","volume":"72","author":"Noyce","year":"2012","journal-title":"Ann Neurol"},{"issue":"1","key":"2026080601020549300_micit62","doi-asserted-by":"publisher","first-page":"e8762","DOI":"10.1371\/journal.pone.0008762","article-title":"Progression of Parkinson\u2019s disease pathology is reproduced by intragastric administration of rotenone in mice.","volume":"5","author":"Pan-Montojo","year":"2010","journal-title":"PLoS One"},{"issue":"44","key":"2026080601020549300_micit63","doi-asserted-by":"publisher","first-page":"e2123","DOI":"10.3791\/2123","article-title":"Oral administration of rotenone using a gavage and image analysis of alpha-synuclein inclusions in the enteric nervous system.","author":"Pan-Montojo","year":"2010","journal-title":"J Vis Exp"},{"key":"2026080601020549300_micit64","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1038\/srep00898","article-title":"Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice.","volume":"2","author":"Pan-Montojo","year":"2012","journal-title":"Sci Rep"},{"issue":"7","key":"2026080601020549300_micit65","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/mds.22534","article-title":"Hyposmia and executive dysfunction as predictors of future Parkinson\u2019s disease: a prospective study.","volume":"24","author":"Ponsen","year":"2009","journal-title":"Mov Disord"},{"issue":"7","key":"2026080601020549300_micit66","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/mds.25037","article-title":"A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study.","volume":"27","author":"Postuma","year":"2012","journal-title":"Mov Disord"},{"issue":"5","key":"2026080601020549300_micit67","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/ana.22282","article-title":"Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder.","volume":"69","author":"Postuma","year":"2011","journal-title":"Ann Neurol"},{"issue":"15","key":"2026080601020549300_micit68","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1212\/01.wnl.0000340980.19702.6e","article-title":"Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder.","volume":"72","author":"Postuma","year":"2009","journal-title":"Neurology"},{"issue":"pt 6","key":"2026080601020549300_micit69","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1093\/brain\/aws093","article-title":"How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder.","volume":"135","author":"Postuma","year":"2012","journal-title":"Brain"},{"issue":"5","key":"2026080601020549300_micit70","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1212\/WNL.0b013e31825dd383","article-title":"Environmental risk factors for REM sleep behavior disorder: a multicenter case-control study.","volume":"79","author":"Postuma","year":"2012","journal-title":"Neurology"},{"issue":"1\u20132","key":"2026080601020549300_micit71","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jns.2011.04.016","article-title":"View point: Etiology in Parkinson\u2019s disease. Dual hit or spreading intoxication.","volume":"310","author":"Reichmann","year":"2011","journal-title":"J Neurol Sci"},{"issue":"12","key":"2026080601020549300_micit72","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1002\/mds.21076","article-title":"Association of olfactory dysfunction with incidental Lewy bodies.","volume":"21","author":"Ross","year":"2006","journal-title":"Mov Disord"},{"issue":"2","key":"2026080601020549300_micit73","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ana.21291","article-title":"Association of olfactory dysfunction with risk for future Parkinson\u2019s disease.","volume":"63","author":"Ross","year":"2008","journal-title":"Ann Neurol"},{"issue":"21","key":"2026080601020549300_micit74","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1212\/WNL.0b013e3181c34af5","article-title":"Medical records documentation of constipation preceding Parkinson disease: a case\u2013control study.","volume":"73","author":"Savica","year":"2009","journal-title":"Neurology"},{"issue":"8","key":"2026080601020549300_micit75","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.sleep.2012.10.009","article-title":"Delayed emergence of a parkinsonian disorder or dementia in 81% of older males initially diagnosed with idiopathic REM sleep behavior disorder (RBD): 16-year update on a previously reported series.","volume":"14","author":"Schenck","year":"2013","journal-title":"Sleep Med"},{"issue":"2","key":"2026080601020549300_micit76","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1212\/WNL.46.2.388","article-title":"Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder.","volume":"46","author":"Schenck","year":"1996","journal-title":"Neurology"},{"issue":"5","key":"2026080601020549300_micit77","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1111\/j.1460-9568.2009.06657.x","article-title":"PPAR-gamma-mediated neuroprotection in a chronic mouse model of Parkinson\u2019s disease.","volume":"29","author":"Schintu","year":"2009","journal-title":"Eur J Neurosci"},{"issue":"4","key":"2026080601020549300_micit78","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/chemse\/bjr102","article-title":"Olfactory impairment in an adult population: the Beaver Dam Offspring Study.","volume":"37","author":"Schubert","year":"2012","journal-title":"Chem Senses"},{"issue":"4","key":"2026080601020549300_micit79","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/lary.21416","article-title":"Olfactory impairment in older adults: five-year incidence and risk factors.","volume":"121","author":"Schubert","year":"2011","journal-title":"Laryngoscope"},{"issue":"6","key":"2026080601020549300_micit80","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/mds.25020","article-title":"Is alpha-synuclein in the colon a biomarker for premotor Parkinson\u2019s disease? Evidence from 3 cases.","volume":"27","author":"Shannon","year":"2012","journal-title":"Mov Disord"},{"issue":"4","key":"2026080601020549300_micit81","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1002\/1531-8257(200007)15:4<669::AID-MDS1011>3.0.CO;2-5","article-title":"Anxiety disorders and depressive disorders preceding Parkinson\u2019s disease: a case-control study.","volume":"15","author":"Shiba","year":"2000","journal-title":"Mov Disord"},{"issue":"6","key":"2026080601020549300_micit82","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/mds.21879","article-title":"The evolution of disability in Parkinson disease.","volume":"23","author":"Shulman","year":"2008","journal-title":"Mov Disord"},{"issue":"15","key":"2026080601020549300_micit83","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1002\/mds.21707","article-title":"Risk factors for Parkinson\u2019s disease and impaired olfaction in relatives of patients with Parkinson\u2019s disease.","volume":"22","author":"Siderowf","year":"2007","journal-title":"Mov Disord"},{"issue":"3","key":"2026080601020549300_micit84","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/mds.24892","article-title":"Impaired olfaction and other prodromal features in the Parkinson At-Risk Syndrome Study.","volume":"27","author":"Siderowf","year":"2012","journal-title":"Mov Disord"},{"issue":"2","key":"2026080601020549300_micit85","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.expneurol.2012.06.035","article-title":"The search for genetic mouse models of prodromal Parkinson\u2019s disease.","volume":"237","author":"Smith","year":"2012","journal-title":"Exp Neurol"},{"issue":"16","key":"2026080601020549300_micit86","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1002\/mds.21740","article-title":"The REM sleep behavior disorder screening questionnaire\u2013a new diagnostic instrument.","volume":"22","author":"Stiasny-Kolster","year":"2007","journal-title":"Mov Disord"},{"issue":"9","key":"2026080601020549300_micit87","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1212\/WNL.0b013e318285c0ed","article-title":"Nonmotor fluctuations in Parkinson disease: Severity and correlation with motor complications.","volume":"80","author":"Storch","year":"2013","journal-title":"Neurology"},{"issue":"8","key":"2026080601020549300_micit88","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1111\/j.1365-2036.2011.04602.x","article-title":"Systematic review: the effects of fibre in the management of chronic idiopathic constipation.","volume":"33","author":"Suares","year":"2011","journal-title":"Aliment Pharmacol Ther"},{"issue":"25","key":"2026080601020549300_micit89","doi-asserted-by":"crossref","first-page":"8103","DOI":"10.1523\/JNEUROSCI.1495-09.2009","article-title":"Nonmotor symptoms of Parkinson\u2019s disease revealed in an animal model with reduced monoamine storage capacity.","volume":"29","author":"Taylor","year":"2009","journal-title":"J Neurosci"},{"issue":"suppl 7","key":"2026080601020549300_micit90","first-page":"S12","article-title":"Diagnosis and the premotor phase of Parkinson disease.","volume":"72","author":"Tolosa","year":"2009","journal-title":"Neurology"},{"issue":"1","key":"2026080601020549300_micit91","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/mds.23346","article-title":"Clinical subtypes of Parkinson\u2019s disease.","volume":"26","author":"van Rooden","year":"2011","journal-title":"Mov Disord"},{"issue":"7","key":"2026080601020549300_micit92","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1002\/mds.22512","article-title":"Motor patterns in Parkinson\u2019s disease: a data-driven approach.","volume":"24","author":"van Rooden","year":"2009","journal-title":"Mov Disord"},{"issue":"8","key":"2026080601020549300_micit93","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s00415-008-0807-9","article-title":"The association between smoking and smell and taste impairment in the general population.","volume":"255","author":"Vennemann","year":"2008","journal-title":"J Neurol"},{"issue":"8","key":"2026080601020549300_micit94","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1097\/WNR.0b013e3282ffda5e","article-title":"Abnormal colonic motility in mice overexpressing human wild-type \u03b1-synuclein.","volume":"19","author":"Wang","year":"2008","journal-title":"Neuroreport"},{"issue":"9","key":"2026080601020549300_micit95","doi-asserted-by":"crossref","first-page":"e425","DOI":"10.1111\/j.1365-2982.2012.01974.x","article-title":"Mice overexpressing wild-type human alpha-synuclein display alterations in colonic myenteric ganglia and defecation.","volume":"24","author":"Wang","year":"2012","journal-title":"Neurogastroenterol Motil"},{"issue":"6","key":"2026080601020549300_micit96","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/mds.10425","article-title":"Prospective study of phobic anxiety and risk of Parkinson\u2019s disease.","volume":"18","author":"Weisskopf","year":"2003","journal-title":"Mov Disord"},{"issue":"5","key":"2026080601020549300_micit97","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1001\/archneurol.2011.2370","article-title":"Predictors of survival in patients with Parkinson disease.","volume":"69","author":"Willis","year":"2012","journal-title":"Arch Neurol"},{"key":"2026080601020549300_micit98","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/j.1749-6632.2009.04013.x","article-title":"Olfactory impairment in presymptomatic Alzheimer\u2019s disease.","volume":"1170","author":"Wilson","year":"2009","journal-title":"Ann NY Acad Sci"},{"issue":"7","key":"2026080601020549300_micit99","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1001\/archpsyc.64.7.802","article-title":"Olfactory identification and incidence of mild cognitive impairment in older age.","volume":"64","author":"Wilson","year":"2007","journal-title":"Arch Gen Psychiatry"}],"container-title":["Environmental Health Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/121\/11-12\/1245\/66427538\/ehp.1306967.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-pdf\/121\/11-12\/1245\/66427538\/ehp.1306967.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:46:45Z","timestamp":1786628805000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/evhpaz\/article-lookup\/doi\/10.1289\/ehp.1306967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,9]]},"references-count":99,"journal-issue":{"issue":"11-12","published-online":{"date-parts":[[2013,8,9]]},"published-print":{"date-parts":[[2013,11,1]]}},"URL":"https:\/\/doi.org\/10.1289\/ehp.1306967","relation":{},"ISSN":["0091-6765","1552-9924"],"issn-type":[{"value":"0091-6765","type":"print"},{"value":"1552-9924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,9]]}}}