{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:03:48Z","timestamp":1792299828658,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS\u20102023\u201000265159"],"award-info":[{"award-number":["RS\u20102023\u201000265159"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While olfactory dysfunction is common in Parkinson disease (PD), its neural basis and clinical implications remain to be clarified. We investigated the neural substrates and clinical profiles, particularly non\u2010motor symptoms (NMSs), associated with olfactory function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study included 259 drug\u2010na\u00efve patients with PD who underwent the Cross\u2010Cultural Smell Identification Test (CC\u2010SIT), comprehensive autonomic function test, neuropsychological assessments, and the Neuropsychiatric Inventory Questionnaire (NPI\u2010Q) at diagnosis. NMS profiles were compared across olfactory groups defined by CC\u2010SIT scores (normosmia [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200945], hyposmia [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009143], anosmia [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200974]). Associations between olfaction and clinical\/imaging variables were assessed using correlation and path analyses. Cox proportional hazards models were employed to evaluate the risk of developing motor complications or PD dementia according to olfactory status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CC\u2010SIT scores correlated with Composite Autonomic Severity Scale scores (rho\u2009=\u2009\u22120.219,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), NPI\u2010Q scores (rho\u2009=\u2009\u22120.269,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and cognitive performance in memory (rho\u2009=\u20090.288,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and frontal\/executive domains (rho\u2009=\u20090.205,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Dopaminergic depletion in the caudate nucleus and limbic atrophy emerged as neural substrates underlying olfactory dysfunction, mediating the association between olfaction and cognitive\/neuropsychiatric symptoms. Anosmia was associated with increased risk of developing PD dementia compared to normosmia (hazard ratio [HR]: 2.579; 95% confidence intervals [CI]: 1.137\u20135.851) and hyposmia (HR: 2.783; 95% CI: 1.437\u20135.390). Anosmia was associated with higher risk of developing freezing of gait (HR: 2.571; 95% CI: 1.077\u20136.134) compared to normosmia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Olfactory dysfunction serves as a multifaceted clinical marker associated with convergent degeneration of nigrostriatal and limbic pathways, offering insights into PD phenotypic variance and its prognostic implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70404","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T19:06:31Z","timestamp":1762283191000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Olfactory Dysfunction as a Window Into the Heterogeneity of Parkinson Disease"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2641-9592","authenticated-orcid":false,"given":"Yeeun","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Neurology Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2093-1641","authenticated-orcid":false,"given":"Han Kyu","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Neurology Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-3965","authenticated-orcid":false,"given":"So Hoon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Neurology National Health Insurance Service Ilsan Hospital  Goyang Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quynh Phuong","family":"Vo","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Medicine and Pharmacy at Ho Chi Minh City  Ho Chi Minh City Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Wook","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5082-1075","authenticated-orcid":false,"given":"Jung Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology Yonsei University College of Medicine  Seoul South 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