{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:05:11Z","timestamp":1790057111309,"version":"4.0.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010101","name":"Taichung Veterans General Hospital","doi-asserted-by":"publisher","award":["TCVGH-1123402C, TCVGH-1133401C, TCVGH-1144503C"],"award-info":[{"award-number":["TCVGH-1123402C, TCVGH-1133401C, TCVGH-1144503C"]}],"id":[{"id":"10.13039\/501100010101","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rapid eye movement (REM) sleep behavior disorder (RBD) and olfactory impairment are common prodromal features of Parkinson\u2019s disease (PD), but the implications of their coexistence remain uncertain. The dual-hit hypothesis proposes concomitant olfactory and enteric involvement, whereas the revised single-hit framework proposes predominantly brain-first or body-first routes. We examined whether probable RBD (pRBD)\/anosmia-defined subgroups exhibit distinct clinical profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, 201 individuals with PD underwent olfactory, cognitive, motor, non-motor, and quality-of-life assessments. Anosmia was defined as a University of Pennsylvania Smell Identification Test score &amp;lt;19 and pRBD as an RBD Screening Questionnaire score \u22656 supplemented by participant and informant interviews. Multivariable models evaluated the main and interactive effects of anosmia and pRBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 201 participants, 95 (47.3%) were pRBD-positive (pRBD+), 135 (67.2%) had anosmia, and 68 (33.8%) had both. Anosmia prevalence did not differ between the pRBD+ and pRBD-negative (pRBD\u2212) groups (71.6% vs. 63.2%;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.208). After adjustment for age, sex, and disease duration, pR+A+ and pR+A\u2212 (subgroups defined by probable RBD status [pR+\/pR\u2212] and anosmia status [A+\/A\u2212]) did not differ in any assessed outcome. The anosmia-by-pRBD interaction was negative for MDS-UPDRS part III (\u03b2 = \u22128.3, 95% CI \u221215.2 to \u22121.4;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.019). Within the pRBD\u2212 subgroup, pR\u2212A+ participants had lower MoCA scores than pR\u2212A\u2212 participants (\u03b2 = \u22122.6; 95% CI \u22124.1 to \u22121.0;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001), and the anosmia-by-pRBD interaction was positive for MoCA (\u03b2 = 2.3, 95% CI 0.0 to 4.5;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.049). Anosmia was associated with cognitive impairment in pRBD\u2212 participants (OR 2.53, 95% CI 1.00\u20136.37;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.049), but not in pRBD+ participants (OR 1.65, 95% CI 0.60\u20134.50;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.331).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In pRBD+ participants, anosmia was not associated with greater motor severity; in pRBD\u2212 participants, it was instead linked to cognitive impairment. Concurrent assessment of olfaction and pRBD may improve clinical phenotyping, but longitudinal validation is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1778012","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:40:33Z","timestamp":1790055633000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Olfactory impairment and probable REM sleep behavior disorder in Parkinson\u2019s disease: clinical relevance to the single- and dual-hit hypotheses"],"prefix":"10.3389","volume":"18","author":[{"given":"Chia-Yen","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurology, Neurological Institute, Taichung Veterans General Hospital","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Hsin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, MacKay Memorial Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurological Institute, Taichung Veterans General Hospital","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurological Institute, Taichung Veterans General Hospital","place":["Taichung, Taiwan"]},{"name":"Department of Post-Baccalaureate Medicine and Brain and Neuroscience Research Center, College of Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1016\/j.clinph.2018.05.003","article-title":"Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies.","volume":"129","author":"Barone","year":"2018","journal-title":"Clin. 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