{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:29:34Z","timestamp":1791473374917,"version":"4.3.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":252,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008487","name":"Cure Parkinson's Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008487","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Current treatments for Parkinson\u2019s disease focus on symptom management, with no therapies yet demonstrated to slow disease progression. Leukotriene receptor antagonists, widely used for asthma, have shown potential neuroprotective effects for Parkinson\u2019s disease in preclinical studies, but have also been associated with an elevated risk of neuropsychiatric events and sleep disorders. We assessed the effect of leukotriene receptor antagonist treatment on the risk of Parkinson\u2019s disease, neuropsychiatric events, and sleep disorders in patients with asthma aged over 50 years. We conducted a cohort study using the UK Clinical Practice Research Datalink between January 2000 and December 2020. The study emulated sequential target trials (n = 140) using observational data, comparing leukotriene receptor antagonist treatment to no leukotriene receptor antagonist treatment among patients aged 50\u201384 years with asthma. The primary outcome was the risk of incident Parkinson\u2019s disease, and the secondary outcomes were neuropsychiatric events (anxiety, depression, and psychosis), and sleep disorders. Propensity score matching was employed to minimize confounding. We used pooled logistic regression models to calculate risk ratios as observational analogues of intention-to-treat and per protocol effects. A total of 97 049 matched pairs were included in the analysis, with 573 Parkinson\u2019s disease cases observed in the leukotriene receptor antagonist group and 537 in the nonleukotriene receptor antagonist group over a median follow-up of 5.9 years and 5.7 years, respectively. No significant difference in Parkinson\u2019s disease risk was observed between the two groups in either the intention-to-treat analysis [10-year risk ratio: 1.09; 95% confidence interval (CI), 0.94\u20131.26] or the per protocol analysis (10-year risk ratio: 0.95; 95% CI, 0.75\u20131.16). However, there was a higher risk of depression (intention-to-treat effect: 10-year risk ratio: 1.12; 95% CI, 1.07\u20131.16; number-needed-to-harm = 93; per protocol effect: 10-year risk ratio: 1.15; 95% CI, 1.08\u20131.22; number-needed-to-harm = 75) and sleep disorders (intention-to-treat effect: 10-year risk ratio: 1.14; 95% CI, 1.11\u20131.19; number-needed-to-harm = 77; per protocol effect: 10-year risk ratio: 1.12; 95% CI, 1.06\u20131.19; number-needed-to-harm = 88) with leukotriene receptor antagonist treatment. No clear effect was observed for anxiety or psychosis. Leukotriene receptor antagonist treatment was not associated with an altered risk of Parkinson\u2019s disease among people aged 50\u201384 years with asthma but was linked to a higher incidence of neuropsychiatric events.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf340","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:01:29Z","timestamp":1757462489000},"source":"Crossref","is-referenced-by-count":3,"title":["Effect of leukotriene receptor antagonist use on the future risk of Parkinson\u2019s disease in older patients with asthma"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-6262","authenticated-orcid":false,"given":"Chengsheng","family":"Ju","sequence":"first","affiliation":[{"name":"Research Department of Practice and Policy, University College London School of Pharmacy , London WC1N 1AX ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Department of Practice and Policy, University College London School of Pharmacy , London WC1N 1AX ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Schrag","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London Institute of Neurology , London WC1N 3BG ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Carroll","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle-upon-Tyne, NE1 7RU ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-1813","authenticated-orcid":false,"given":"Thomas","family":"Foltynie","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London Institute of Neurology , London WC1N 3BG ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8840-7267","authenticated-orcid":false,"given":"Li","family":"Wei","sequence":"additional","affiliation":[{"name":"Research Department of Practice and Policy, University College London School of Pharmacy , London WC1N 1AX ,","place":["United Kingdom"]},{"name":"Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park , Hong Kong Special Administrative Region ,","place":["China"]},{"name":"Centre for Medicines Optimisation Research and Education, University College London Hospitals National Health Service (NHS) Foundation Trust , London NW1 2PG ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"2025092304112837200_fcaf340-B1","author":"Parkinson's UK","year":"2018"},{"issue":"s1","key":"2025092304112837200_fcaf340-B2","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The emerging evidence of the Parkinson pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J Parkinsons Dis"},{"key":"2025092304112837200_fcaf340-B3","author":"Gumber","year":"2017"},{"issue":"5","key":"2025092304112837200_fcaf340-B4","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3233\/JPD-240272","article-title":"Parkinson's disease drug therapies in the clinical trial pipeline: 2024 update","volume":"14","author":"McFarthing","year":"2024","journal-title":"J Parkinsons Dis"},{"key":"2025092304112837200_fcaf340-B5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.2147\/DDDT.S39100","article-title":"Clinical effectiveness and safety of montelukast in asthma. What are the conclusions from clinical trials and meta-analyses?","volume":"8","author":"Hon","year":"2014","journal-title":"Drug Des Devel Ther"},{"key":"2025092304112837200_fcaf340-B6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.neulet.2018.05.052","article-title":"Effect of montelukast in experimental model of Parkinson's disease","volume":"682","author":"Nagarajan","year":"2018","journal-title":"Neurosci Lett"},{"issue":"5","key":"2025092304112837200_fcaf340-B7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/WNR.0000000000000740","article-title":"Montelukast treatment protects nigral dopaminergic neurons against microglial activation in the 6-hydroxydopamine mouse model of Parkinson's disease","volume":"28","author":"Jang","year":"2017","journal-title":"Neuroreport"},{"key":"2025092304112837200_fcaf340-B8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.taap.2018.09.012","article-title":"Montelukast attenuates rotenone-induced microglial activation\/p38 MAPK expression in rats: Possible role of its antioxidant, anti-inflammatory and antiapoptotic effects","volume":"358","author":"Mansour","year":"2018","journal-title":"Toxicol Appl Pharmacol"},{"issue":"5","key":"2025092304112837200_fcaf340-B9","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/ana.26638","article-title":"beta2-adrenoreceptor Agonists, Montelukast, and Parkinson disease risk","volume":"93","author":"Liu","year":"2023","journal-title":"Ann Neurol"},{"key":"2025092304112837200_fcaf340-B10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12979-017-0102-7","article-title":"Prescription database analyses indicates that the asthma medicine montelukast might protect against dementia: A hypothesis to be verified","volume":"14","author":"Grinde","year":"2017","journal-title":"Immun 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