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universitetssjukhus","doi-asserted-by":"publisher","award":["2020-O000028"],"award-info":[{"award-number":["2020-O000028"]}],"id":[{"id":"10.13039\/501100011077","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Olfactory dysfunction is a common non-motor symptom in Parkinson\u2019s disease (PD). The objective was to evaluate the association between olfaction in PD with cross-sectional and longitudinal assessments of clinical variables and novel cerebrospinal fluid (CSF) markers.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients with PD and baseline olfactory function assessed using the Brief Smell Identification Test (B-SIT) were included from the BioFINDER-1 cohort. Clinical variables, CSF measures and disease status were assessed longitudinally for up to 11 years. CSF was analyzed using Roche Elecsys\u00ae NeuroToolKit, including biomarkers of neurodegeneration, glial activation, neuroinflammation and the core Alzheimer disease biomarkers.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 172 patients with PD were included, 63 with normal olfactory function and 109 with hyposmia. No differences were seen in clinical variables at baseline. Glial fibrillary acidic protein was the only CSF marker differing at baseline, being elevated in hyposmic patients with PD (12.25\u2009\u00b1\u20093.87 vs 10.46\u2009\u00b1\u20093.68, p\u2009=\u20090.001). At follow-up, olfactory function declined predominantly in patients with normal olfaction at baseline (\u03b2\u2009=\u2009\u22120.25 [\u22120.40 to \u22120.12], p\u2009=\u20090.001). Patients with PD with both olfactory dysfunction and amyloid-positivity (defined by the CSF A\u03b242\/A\u03b240 ratio) declined faster in several cognitive and motor measures. Olfaction and amyloid-status were independently associated with increased risk of progressing to dementia (B-SIT score, HR\u2009=\u20090.77 [0.67\u20130.88] and amyloid-positivity, HR\u2009=\u20094.47 [2.30\u20138.67]).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Olfactory dysfunction and amyloid-positivity are independently associated with a higher rate of cognitive decline and progression to dementia in patients with PD. Novel CSF markers of neurodegeneration and glial-activity do not differ depending on olfactory status in PD.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0325560","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:27:41Z","timestamp":1755797261000},"page":"e0325560","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Olfactory dysfunction and amyloid-positivity in Parkinson\u2019s disease\u2014longitudinal analysis of cognitive decline and cerebrospinal fluid markers"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8769-7909","authenticated-orcid":true,"given":"Victoria","family":"Larsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Hansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"pone.0325560.ref001","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"W Poewe","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"pone.0325560.ref002","doi-asserted-by":"crossref","first-page":"776847","DOI":"10.3389\/fpubh.2021.776847","article-title":"Global trends in the incidence, prevalence, and years lived with disability of Parkinson\u2019s disease in 204 countries\/territories from 1990 to 2019","volume":"9","author":"Z Ou","year":"2021","journal-title":"Front Public Health"},{"issue":"12","key":"pone.0325560.ref003","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease","volume":"30","author":"RB Postuma","year":"2015","journal-title":"Mov Disord"},{"issue":"5","key":"pone.0325560.ref004","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s12264-017-0170-x","article-title":"Olfactory dysfunction as an early biomarker in parkinson\u2019s disease","volume":"33","author":"ME Fullard","year":"2017","journal-title":"Neurosci Bull"},{"issue":"8","key":"pone.0325560.ref005","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1007\/s00415-018-8913-9","article-title":"Correlation among olfactory function, motors\u2019 symptoms, cognitive impairment, apathy, and fatigue in patients with Parkinson\u2019s disease","volume":"265","author":"C Masala","year":"2018","journal-title":"J Neurol"},{"issue":"5","key":"pone.0325560.ref006","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/jnen\/61.5.413","article-title":"Where does parkinson disease pathology begin in the brain?","volume":"61","author":"K Del Tredici","year":"2002","journal-title":"J Neuropathol Exp Neurol"},{"issue":"2","key":"pone.0325560.ref007","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":"H Braak","year":"2003","journal-title":"Neurobiol Aging"},{"issue":"4","key":"pone.0325560.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0231720","article-title":"Severe hyposmia distinguishes neuropathologically confirmed dementia with Lewy bodies from Alzheimer\u2019s disease dementia","volume":"15","author":"TG Beach","year":"2020","journal-title":"PLoS One"},{"key":"pone.0325560.ref009","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jns.2011.05.030","article-title":"Neuropsychological correlates of olfactory dysfunction in Parkinson\u2019s disease","volume":"310","author":"JF Morley","year":"2011","journal-title":"J Neurol Sci"},{"issue":"5","key":"pone.0325560.ref010","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3390\/brainsci12050513","article-title":"Does olfactory dysfunction correlate with disease progression in Parkinson\u2019s disease? 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