{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:56:08Z","timestamp":1793217368893,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>It is shown that the circadian system is affected in patients with Alzheimer\u2019s disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning <jats:italic>via<\/jats:italic> a direct effect or indirectly <jats:italic>via<\/jats:italic> its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild\/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.<\/jats:p>","DOI":"10.3389\/fphys.2021.755322","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T05:17:00Z","timestamp":1641446220000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer\u2019s Disease: Preliminary Findings in a Pivotal Study"],"prefix":"10.3389","volume":"12","author":[{"given":"Riccardo","family":"Cremascoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Sparasci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Giusti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Cattaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Prina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Roveta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ghezzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cerri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Picascia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bernini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sinforiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Terzaghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Priano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Mauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Manni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-012759","article-title":"Systematic review of systematic reviews of non-pharmacological interventions to treat behavioural disturbances in older patients with dementia.","volume":"7","author":"Abraha","year":"2017","journal-title":"BMJ Open"},{"key":"B2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1207\/S15402010BSM0101_4","article-title":"Increased light exposure consolidates sleep and strengthens circadian rhythms in severe Alzheimer\u2019s Disease patients.","volume":"1","author":"Ancoli-Israel","year":"2003","journal-title":"Behav. Sleep Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.smrv.2008.04.009","article-title":"A practical approach to circadian rhythm sleep disorders.","volume":"13","author":"Bjorvatn","year":"2009","journal-title":"Sleep Med. Rev."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075893","article-title":"The Acute Side Effects of Bright Light Therapy: a Placebo-Controlled Investigation.","volume":"8","author":"Botanov","year":"2013","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s10072-012-1085-y","article-title":"Validity of the Italian version of the Pittsburgh Sleep Quality Index (PSQI).","volume":"34","author":"Curcio","year":"2013","journal-title":"Neurol. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1002\/gps.852","article-title":"Bright light treatment improves sleep in institutionalised elderly\u2014an open trial.","volume":"18","author":"Fetveit","year":"2003","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.5664\/jcsm.8078","article-title":"Effects of a tailored lighting intervention on sleep quality, rest-activity, mood, and behavior in older adults with Alzheimer disease and related dementias: a randomized clinical trial.","volume":"15","author":"Figueiro","year":"2019","journal-title":"J. Clin. Sleep Med."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003946.pub4","article-title":"Light therapy for improving cognition, activities of daily living, sleep, challenging behaviour, and psychiatric disturbances in dementia.","author":"Forbes","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1001\/jama.2019.8295","article-title":"For Alzheimer pathology, light and sound stimulation may hold promise.","volume":"322","author":"Hampton","year":"2019","journal-title":"JAMA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.4062\/biomolther.2019.192","article-title":"Impact of sleep disorder as a risk factor for dementia in men and women.","volume":"28","author":"Jee","year":"2020","journal-title":"Biomol. Ther."},{"key":"B11","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/(SICI)1099-1166(199907)14:7<520::AID-GPS983>3.0.CO;2-M","article-title":"A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care.","volume":"14","author":"Lyketsos","year":"1999","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.sleep.2019.04.018","article-title":"Evening melatonin timing secretion in real-life conditions in patients with Alzheimer disease of mild to moderate severity.","volume":"63","author":"Manni","year":"2019","journal-title":"Sleep Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease.","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimers Dement."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0447.1994.tb01477.x","article-title":"Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia.","volume":"89","author":"Mishima","year":"1994","journal-title":"Acta Psychiatr. Scand."},{"key":"B15","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/s0006-3223(97)00510-6","article-title":"Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer\u2019s type with disturbed sleep-waking","volume":"45","author":"Mishima","year":"1999","journal-title":"Biol. Psychiatry."},{"key":"B16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1684\/pnv.2019.0786","article-title":"Role of \u201clight therapy\u201d among older adults with dementia: an overview and future perspectives.","volume":"17","author":"Missotten","year":"2019","journal-title":"Geriatr. Psychol. Neuropsychiatr. Vieil."},{"key":"B17","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1159\/000494921","article-title":"Effects of light treatment on sleep, cognition, mood, and behavior in Alzheimer\u2019s disease: a systematic review.","volume":"46","author":"Mitolo","year":"2018","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"B18","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.maturitas.2019.06.007","article-title":"Non-pharmacological treatments for sleep disturbance in mild cognitive impairment and dementia: a systematic review and meta-analysis.","volume":"127","author":"O\u2019Caoimh","year":"2019","journal-title":"Maturitas"},{"key":"B19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pnpbp.2006.06.020","article-title":"Dim light melatonin onset (DLMO): a tool for the analysis of circadian phase in human sleep and chronobiological disorders.","volume":"31","author":"Pandi-Perumal","year":"2007","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.sleep.2011.11.008","article-title":"Laboratory validation of an in-home method for assessing circadian phase using dim light melatonin onset (DLMO).","volume":"13","author":"Pullman","year":"2012","journal-title":"Sleep Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/B978-0-444-53817-8.00001-3","article-title":"Cognition in circadian rhythm sleep disorders.","volume":"190","author":"Reid","year":"2011","journal-title":"Prog. Brain Res."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-017-0745-y","article-title":"Circadian disruption associated with Alzheimer\u2019s Disease.","volume":"17","author":"Saeed","year":"2017","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/s0531-5565(02)00198-5","article-title":"Melatonin rhythmicity: effect of age and Alzheimer\u2019s disease.","volume":"38","author":"Skene","year":"2003","journal-title":"Exp. Gerontol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1177\/1477153513517255","article-title":"Effect of home-based light treatment on persons with dementia and their caregivers.","volume":"47","author":"Sloane","year":"2015","journal-title":"Light. Res. Technol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1080\/07420528.2018.1527773","article-title":"Systematic review of light exposure impact on human circadian rhythm.","volume":"36","author":"T\u00e4hk\u00e4m\u00f6","year":"2019","journal-title":"Chronobiol. Int."},{"key":"B26","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/S0006-3223(97)89928-3","article-title":"Indirect bright light improves circadian rest-activity rhythm disturbances in demented patients.","volume":"41","author":"Van Someren","year":"1997","journal-title":"Biol. Psychiatry"},{"key":"B27","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3109\/07420529908998724","article-title":"Bright Light Therapy: improved sensitivity to its effects on rest-activity rhythms in Alzheimer patients by application of nonparametric methods.","volume":"16","author":"Van Someren","year":"1999","journal-title":"Chronobiol. Int."},{"key":"B28","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s100720300004","article-title":"Italian version of the Epworth sleepiness scale: external validity.","volume":"23","author":"Vignatelli","year":"2003","journal-title":"Neurol. Sci."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2012.00050","article-title":"Circadian and wakefulness-sleep modulation of cognition in humans.","volume":"5","author":"Wright","year":"2012","journal-title":"Front. Mol. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1046\/j.1440-1819.2000.00711.x","article-title":"Effects of bright light on cognitive and sleep-wake (circadian) rhythm disturbances in Alzheimer-type dementia.","volume":"54","author":"Yamadera","year":"2000","journal-title":"Psychiatry Clin. Neurosci."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.755322\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T05:17:05Z","timestamp":1641446225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.755322\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,6]]},"references-count":30,"alternative-id":["10.3389\/fphys.2021.755322"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.755322","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,6]]},"article-number":"755322"}}