{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:14:31Z","timestamp":1792610071754,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: The involvement of the circadian system in the etiology and treatment of Parkinson\u2019s disease (PD) is becoming an increasingly important topic. The prodromal symptoms of PD include insomnia, fatigue, depression and sleep disturbance which herald the onset of the primary symptoms of bradykinesia, tremor and rigidity while robbing patients of their quality of life. Light treatment (LT) has been implemented for modifying circadian function in PD but few studies have examined its use in a protracted term that characterizes PD itself. Methods: The present exploratory study monitors the effect of LT over a 10 year course of PD in the context of ongoing circadian function. Results: Improvement in circadian based symptoms were seen soon after LT commenced and continued for the duration of the study. Improvement in motor function was more subtle and was not distinguishable until 1.2 years after commencing treatment. Improvement in most motor and prodromal symptoms remained in steady state for the duration of the study as long as patients were compliant with daily use. Conclusions: The sequence of improvement in prodromal symptoms and motor function seen here parallels the slow, incremental repair process mimicking the protracted degenerative sequelae of PD that extends over decades. This process also emulates the slow incremental improvement characterizing the reparative course seen with circadian symptoms in other disorders that improve with LT. Recent findings from epidemiological work suggest that early disruption of circadian rhythmicity is associated with increased risk of PD and the present findings are consistent with that hypothesis. It is concluded that intervening in circadian function with LT presents a minimally invasive method that is compatible with internal timing that slows the degenerative process of PD.<\/jats:p>","DOI":"10.3390\/brainsci14121218","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:43:43Z","timestamp":1733118223000},"page":"1218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Circadian Intervention Improves Parkinson\u2019s Disease and May Slow Disease Progression: A Ten Year Retrospective Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Gregory","family":"Willis","sequence":"first","affiliation":[{"name":"The Bronowski Clinic, The Bronowski Institute of Behavioral Neuroscience, Woodend, VIC 3442, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuyuki","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Osaka Toneyama Medical Center, 5-1-1, Toneyama, Toyonaka 560-8552, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Waldman","sequence":"additional","affiliation":[{"name":"Sunnex Biotechnologies, 657-167 Lombard Ave, Winnipeg, MB R3B 0V3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1007\/s00415-020-10089-x","article-title":"Dopaminergic therapy and prefrontal activation during waking in individuals with Parkinson\u2019s disease: Does the levodopa overdose hypothesis extend to gait?","volume":"268","author":"Dagan","year":"2021","journal-title":"J. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e148288","DOI":"10.1172\/JCI148288","article-title":"Defining circadian disruption in neurodegenerative diseases","volume":"131","author":"Colwell","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.tins.2018.03.002","article-title":"Light Therapy in Parkinson\u2019s disease: Towards Mechanism-Based Protocols","volume":"41","author":"Fifel","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_4","first-page":"63","article-title":"The phototherapy for Parkinson\u2019s patients","volume":"96","author":"Artemenko","year":"1996","journal-title":"Zhurnal Nevrologii i Psikhiatrii Imeni SS Korsakova"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1002\/mds.21542","article-title":"Bright Light Therapy in Parkinson\u2019s disease: A Pilot Study","volume":"22","author":"Paus","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/07420520701420717","article-title":"Primary and secondary features of Parkinson\u2019s disease improve with strategic exposure to bright light: Case series study","volume":"24","author":"Willis","year":"2007","journal-title":"Chronobiol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1515\/revneuro-2011-0072","article-title":"Historical justification for and retrospective analysis of the systematic application of light therapy in Parkinson\u2019s disease","volume":"23","author":"Willis","year":"2012","journal-title":"Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Willis, G.L., Boda, J., and Freelance, C.B. (2018). Polychromatic Light Exposure as a Therapeutic in the Treatment and Management of Parkinson\u2019s disease: A Controlled Exploratory Trial. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00741"},{"key":"ref_9","first-page":"1906271","article-title":"Blue light therapy glasses in Parkinson\u2019s disease: Patients\u2019 experience","volume":"2019","author":"Smilowska","year":"2019","journal-title":"Park. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Endo, T., Matsumura, R., Tokuda, I.T., Yoshikawa, T., Shigeyoshi, Y., Node, K., Sakoda, S., and Akashi, M. (2020). Bright light improves sleep in patients with Parkinson\u2019s disease: Possible role of circadian restoration. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-64645-6"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.sleep.2018.01.001","article-title":"The effect of light exposure on insomnia and nocturnal movement in Parkinson\u2019s disease: An open label, retrospective, longitudinal study","volume":"44","author":"Martino","year":"2018","journal-title":"Sleep Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1001\/jamaneurol.2016.5192","article-title":"Timed light therapy for sleep and daytime sleepiness associated with Parkinson\u2019s disease: A randomised clinical trial","volume":"74","author":"Videnovic","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1145","DOI":"10.1212\/WNL.0000000000007090","article-title":"Bright light therapy for depression in Parkinson\u2019s disease: A randomised controlled trial","volume":"92","author":"Rutten","year":"2019","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.parkreldis.2013.03.003","article-title":"Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinson\u2019s disease\u2014A randomised study","volume":"19","author":"Romenets","year":"2013","journal-title":"Park. Relat. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s13760-019-01214-3","article-title":"Bright light therapy with head-mounted device for anxiety, depression, sleepiness, and fatigue in patients with Parkinson\u2019s disease","volume":"119","author":"Raymackers","year":"2019","journal-title":"Acta Neurol. Belg."},{"key":"ref_16","first-page":"97","article-title":"A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms","volume":"4","author":"Horne","year":"1976","journal-title":"Int. J. Chronobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/00002826-200303000-00005","article-title":"Study of circadian melatonin secretion pattern at different stages of Parkinson\u2019s disease","volume":"26","author":"Bordet","year":"2003","journal-title":"Clin. Neuropharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF02251135","article-title":"Circadian secretion pattern of melatonin in Parkinson\u2019s disease","volume":"3","author":"Fertl","year":"1991","journal-title":"J. Neural. Transm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.sleep.2021.06.023","article-title":"Circadian activity rhythm in Parkinson\u2019s disease: Findings from the PHASE study","volume":"85","author":"Obayashi","year":"2021","journal-title":"Sleep Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1002\/mds.27790","article-title":"Measuring Parkinson\u2019s disease over time: The real world within subject reliability of the MDS-UPDRS","volume":"34","author":"Evers","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_21","first-page":"1765220","article-title":"An investigation into the use and meaning of Parkinson\u2019s disease Clinical Scale Scores","volume":"2021","author":"Hendricks","year":"2021","journal-title":"Park. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1017\/S0317167100038099","article-title":"Progressive Supranuclear Palsy","volume":"14","author":"Duvoisin","year":"1987","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12673","DOI":"10.1111\/jsr.12673","article-title":"An overview of sleep and circadian dysfunction in Parkinson\u2019s disease","volume":"27","author":"Mantovani","year":"2018","journal-title":"J. Sleep. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sateia, M.J. (2014). International Classification of Sleep Disorders, Elsevier. [3rd ed.].","DOI":"10.1378\/chest.14-0970"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/mds.25037","article-title":"A single question screen for rapid eye movement sleep disorder: A multicentre validation study","volume":"27","author":"Postuma","year":"2012","journal-title":"Mov. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4103\/2229-3485.83221","article-title":"Intention-to-treat concept: A review","volume":"2","author":"Gupta","year":"2011","journal-title":"Perspect. Clin. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1749-6632.1985.tb11815.x","article-title":"Immediate and delayed effects of bright light on human melatonin production: Shifting \u201cdawn\u201d and \u201cdusk\u201d shifts the dime light melatonin onset (DLMO)","volume":"453","author":"Lewy","year":"1985","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/B978-0-12-804766-8.00014-5","article-title":"Parkinson\u2019s disease: Diagnosis and appreciation of comorbidities","volume":"167","author":"Deeb","year":"2019","journal-title":"Handb. Clin. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1177\/074873049701200627","article-title":"Toxicology of Melatonin","volume":"12","year":"1997","journal-title":"J. Biol. Rhythm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.mehy.2009.01.047","article-title":"An association between geometric activity and dream bizarreness","volume":"73","author":"Lipnicki","year":"2009","journal-title":"Med. Hyp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1001\/jamaneurol.2020.1623","article-title":"Association of Circadian Abnormalities in Older Adults with an Increased Risk of Developing Parkinson Disease","volume":"77","author":"Leng","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1002\/mds.27461","article-title":"Fatigue in Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"33","author":"Siciliano","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s11910-013-0409-5","article-title":"Depression and Parkinson\u2019s disease: Current Knowledge","volume":"13","author":"Marsh","year":"2013","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yalcin, M., Mundorf, A., Thiel, F., Amatrianin-Fernandez, S., Kalthoff, I.S., Beucke, J.C., Budde, H., Garthus-Niegel, S., Peterburs, J., and Relogio, A. (2022). It\u2019s about time: The circadian network as time-keeper for cognitive functioning, locomotor activity and mental health. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.873237"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1016\/j.metabol.2014.10.030","article-title":"Biomarkers of Parkinson\u2019s disease: Present and future","volume":"64","author":"Miller","year":"2014","journal-title":"Metabolism"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00415-006-0390-x","article-title":"Effect of endogenous melatonin on sleep and motor dysfunction in Parkinson\u2019s disease. A randomized, double blind, placebo-controlled study","volume":"254","author":"Medeiros","year":"2007","journal-title":"J. Neurol."},{"key":"ref_37","first-page":"77","article-title":"The use of melatonin in the treatment of chronic fatigue syndrome and circadian rhythm disorders in Parkinson\u2019s disease","volume":"113","author":"Datieva","year":"2013","journal-title":"Zh. Nevrol. Psikhiatr. Im. S. S. Korsakova."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105878","DOI":"10.1016\/j.clineuro.2020.105878","article-title":"Melatonin supplementation and the effects on clinical and metabolic status in Parkinson\u2019s disease: A randomized, double-blind, placebo-controlled trial","volume":"195","author":"Kakhaki","year":"2020","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0031-9384(99)00023-2","article-title":"A therapeutic role for melatonin antagonism in experimental models of Parkinson\u2019s disease","volume":"66","author":"Willis","year":"1999","journal-title":"Physiol. Behav."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1515\/REVNEURO.2008.19.4-5.245","article-title":"Parkinson\u2019s disease as a neuroendocrine disorder of circadian function: Dopamine-melatonin imbalance and the visual system in the genesis and progression of the degenerative process","volume":"19","author":"Willis","year":"2008","journal-title":"Rev. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.pbb.2004.10.022","article-title":"Recovery of experimental Parkinson\u2019s disease in the methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine treated marmoset with the melatonin analogue ML-23. Pharmacol","volume":"80","author":"Willis","year":"2005","journal-title":"Biochem. Behav."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102474","DOI":"10.1016\/j.eclinm.2024.102474","article-title":"Efficacy of biologically-directed daylight therapy on sleep and circadian rhythm in Parkinson\u2019s disease: A randomised, double-blind, parallel-group, active-controlled, phase II clinical trial","volume":"69","author":"Feigl","year":"2024","journal-title":"EClinicalMedicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1749-6632.1977.tb39716.x","article-title":"Tonic and phasic effects of light in entrainment of circadian rhythms","volume":"290","author":"Dann","year":"1977","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1515\/revneuro-2023-0026","article-title":"Fine-tuning the circadian system with light treatment for Parkinson\u2019s disease: An in-depth, critical review","volume":"35","author":"Willis","year":"2023","journal-title":"Rev. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1002\/mds.23429","article-title":"Systematic review of levodopa dose equivalency reporting in Parkinson\u2019s disease","volume":"25","author":"Tomlinson","year":"2010","journal-title":"Mov. Disord."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/12\/1218\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:43:48Z","timestamp":1760114628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/12\/1218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,30]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["brainsci14121218"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14121218","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,30]]}}}