{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T19:11:30Z","timestamp":1784056290023,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Aging","award":["R01 AG031110, U01 AG051406; R01 AG070028; U19 AG068054"],"award-info":[{"award-number":["R01 AG031110, U01 AG051406; R01 AG070028; U19 AG068054"]}]},{"name":"National Institute on Child Health and Human Development","award":["U54 HD09025"],"award-info":[{"award-number":["U54 HD09025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Adults with Down syndrome are at a high risk for disordered sleep. These sleep problems could have marked effects on aging and Alzheimer\u2019s disease, potentially altering white matter integrity. This study examined the associations between disordered sleep assessed via an actigraph accelerometer worn on 7 consecutive nights, presence of diagnosis of obstructive sleep apnea, and diffusion tensor imaging indices of white matter integrity in 29 non-demented adults with Down Syndrome (48% female, aged 33\u201354 years). Average total sleep time was associated with lower mean diffusivity in the left superior longitudinal fasciculus (r = \u22120.398, p = 0.040). Average sleep efficiency, length of awakenings, and movement index were related to fractional anisotropy in the right inferior longitudinal fasciculus (r = \u22120.614 to 0.387, p \u2264 0.050). Diagnosis of obstructive sleep apnea was associated with fractional anisotropy in the right inferior longitudinal fasciculus (r = \u22120.373, p = 0.050). Findings suggest that more disrupted sleep is associated with lower white matter integrity in the major association tracts in middle-aged adults with Down syndrome. Longitudinal work is needed to confirm the directionally of associations. Sleep interventions could be an important component for promoting optimal brain aging in the Down syndrome population.<\/jats:p>","DOI":"10.3390\/brainsci11101322","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T09:24:04Z","timestamp":1633598644000},"page":"1322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Sleep and White Matter in Adults with Down Syndrome"],"prefix":"10.3390","volume":"11","author":[{"given":"Victoria","family":"Fleming","sequence":"first","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"School of Human Ecology, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3330-441X","authenticated-orcid":false,"given":"Brianna","family":"Piro-Gambetti","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"School of Human Ecology, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Bazydlo","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Department of Medical Physics, University of Wisconsin-Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Zammit","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Department of Medical Physics, University of Wisconsin-Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Department of Medical Physics, University of Wisconsin-Madison, WI 53705, USA"},{"name":"Department of Psychiatry, University of Wisconsin-Madison, WI 53719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Christian","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Department of Medical Physics, University of Wisconsin-Madison, WI 53705, USA"},{"name":"Department of Psychiatry, University of Wisconsin-Madison, WI 53719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Handen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Plante","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Wisconsin-Madison, WI 53719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigan L.","family":"Hartley","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"School of Human Ecology, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/bdr2.1589","article-title":"National population-based estimates for major birth defects, 2010\u20132014","volume":"111","author":"Mai","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1001\/jamaneurol.2019.3666","article-title":"Epidemiology of dementia and alzheimer disease in individuals with down syndrome","volume":"77","author":"Rubenstein","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S1474-4422(10)70112-5","article-title":"Cognitive deficits and associated neurological complications in individuals with down\u2019s syndrome","volume":"9","author":"Lott","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1046\/j.1365-2788.1998.00135.x","article-title":"Maladaptive behaviours and symptoms of dementia in adults with down\u2019s syndrome compared with adults with intellectual disability of other Aatiologies","volume":"42","author":"Cooper","year":"2002","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fan, Z., Ahn, M., Roth, H., Li, L., and Vaughn, B. (2017). Sleep apnea and hypoventilation in patients with down syndrome: Analysis of 144 polysomnogram studies. Children, 4.","DOI":"10.3390\/children4070055"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.5664\/jcsm.27541","article-title":"Obstructive sleep apnea in adults with down syndrome","volume":"5","author":"Trois","year":"2009","journal-title":"J. Clin. Sleep Med."},{"key":"ref_7","first-page":"132","article-title":"Obstructive sleep apnea in children with down syndrome","volume":"88","author":"Marcus","year":"1991","journal-title":"Pediatr. Off. J. Am. Acad. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3104\/reports.138","article-title":"Sleep related breathing disorders in adults with down syndrome","volume":"8","author":"Resta","year":"2003","journal-title":"Down Syndr. Res. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.5664\/jcsm.7382","article-title":"Prevalence of sleep disorders in adults with down syndrome: A comparative study of self-reported, actigraphic, and polysomnographic findings","volume":"14","author":"Videla","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.ijporl.2010.03.050","article-title":"Body mass index as an indicator of obstructive sleep apnea in pediatric down syndrome","volume":"74","author":"Shires","year":"2010","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_11","first-page":"OA4754","article-title":"A prospective, randomised, controlled trial of CPAP in adults with down syndrome","volume":"46","author":"Hill","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Stores, R.J. (2019). Sleep problems in adults with down syndrome and their family carers. J. Appl. Res. Intellect. Disabil., 32.","DOI":"10.1111\/jar.12572"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neurobiolaging.2020.04.018","article-title":"Association of sleep with cognition and beta amyloid accumulation in adults with down syndrome","volume":"93","author":"Cody","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.5665\/sleep.6104","article-title":"Sleep duration and white matter quality in middle-aged adults","volume":"39","author":"Yaffe","year":"2016","journal-title":"Sleep"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1002\/hbm.23739","article-title":"Associations between self-reported sleep quality and white matter in community-dwelling older adults: A prospective cohort study","volume":"38","author":"Sexton","year":"2017","journal-title":"Hum. Brain Mapp."},{"key":"ref_16","first-page":"1","article-title":"The prospective association of Objectively measured sleep and cerebral white matter microstructure in middle-aged and older persons","volume":"42","author":"Kocevska","year":"2019","journal-title":"Sleep"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.trci.2019.02.001","article-title":"White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities","volume":"5","author":"Alber","year":"2019","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1161\/STROKEAHA.119.028143","article-title":"Pervasive white matter fiber degeneration in ischemic stroke","volume":"51","author":"Egorova","year":"2020","journal-title":"Stroke"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11910-021-01094-2","article-title":"Obstructive sleep apnea and the brain: A focus on gray and white matter structure","volume":"21","author":"Baril","year":"2021","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"361","DOI":"10.5665\/sleep.4490","article-title":"White matter damage and systemic inflammation in obstructive sleep apena","volume":"38","author":"Chen","year":"2015","journal-title":"Sleep"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s40675-021-00210-5","article-title":"The link between obstructive sleep apnoea and neurodegeneration and cognition","volume":"7","author":"Weihs","year":"2021","journal-title":"Curr. Sleep Med. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/sleep\/zsz120","article-title":"Altered structural brain network resulting from white matter injury in obstructive sleep apnea","volume":"42","author":"Lee","year":"2019","journal-title":"Sleep"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.sleep.2020.06.024","article-title":"White matter alterations in patients with obstructive sleep apnea: A systematic review of diffusion MRI studies","volume":"75","author":"Rostampour","year":"2020","journal-title":"Sleep Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/jir.12390","article-title":"A prospective 20-year longitudinal follow-up of dementia in persons with down syndrome","volume":"61","author":"McCarron","year":"2017","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_25","first-page":"1","article-title":"Characteristics of adults with down syndrome: Prevalence of age-related conditions","volume":"1","author":"Antocicco","year":"2014","journal-title":"Front. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ejim.2015.05.003","article-title":"Clinical profile and main comorbidities of spanish adults with down Ssndrome","volume":"26","author":"Quero","year":"2015","journal-title":"Eur. J. Intern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/mrm.1910360612","article-title":"Toward a quantitative assessment of diffusion anisotropy","volume":"36","author":"Pierpaoli","year":"1996","journal-title":"Magn. Reson. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tournier, J.D., Smith, R., Raffelt, D., Tabbara, R., Dhollander, T., Pietsch, M., Christiaens, D., Jeurissen, B., Yeh, C.H., and Connelly, A. (2019). MRtrix3: A fast, flexible and open softwareframework for medical image processing and visualisation. NeuroImage, Academic Press Inc.","DOI":"10.1101\/551739"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fninf.2014.00008","article-title":"Dipy, a library for the analysis of diffusion MRI data","volume":"8","author":"Garyfallidis","year":"2014","journal-title":"Front. Neuroinf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/mrm.20426","article-title":"RESTORE: Robust estimation of tensors by outlier rejection","volume":"53","author":"Chang","year":"2005","journal-title":"Magn. Reson. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/sleep\/15.5.461","article-title":"Automatic sleep\/wake identification from wrist activity","volume":"15","author":"Cole","year":"1992","journal-title":"Sleep"},{"key":"ref_32","first-page":"39","article-title":"Reliability of Actigraphy and Subjective Sleep Measurements in Adults: The Design of Sleep Assessments","volume":"13","author":"Aili","year":"2017","journal-title":"J. Clin. Sleep Med. JCSM Off. Publ. Am. Acad. Sleep Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.smrv.2010.10.001","article-title":"The role and validity of actigraphy in sleep medicine: An update","volume":"15","author":"Sadeh","year":"2011","journal-title":"Sleep Med. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.5664\/jcsm.7230","article-title":"Use of Actigraphy for the Evaluation of Sleep Disorders and Circadian Rhythm Sleep-Wake Disorders: An American Academy of Sleep Medicine Clincial Practice Guideline","volume":"14","author":"Smith","year":"2018","journal-title":"J. Clin. Sleep Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"709","DOI":"10.5665\/sleep.2632","article-title":"Obstructive sleep apnea as a risk factor for cerebral white matter change in a middle-aged and older general population","volume":"36","author":"Kim","year":"2013","journal-title":"Sleep"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9626831","DOI":"10.1155\/2016\/9626831","article-title":"Role of oxidative stress in the neurocognitive dysfunction of obstructive sleep apnea syndrome","volume":"2016","author":"Zhou","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/jsr.12177","article-title":"Sleep duration is associated with white matter hyperintensity volume in older adults: The northern manhattan study","volume":"23","author":"Ramos","year":"2014","journal-title":"J. Sleep Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40478-018-0515-3","article-title":"White matter changes in alzheimer\u2019s disease: A focus on myelin and oligodendrocytes","volume":"6","author":"Nasrabady","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_39","first-page":"576","article-title":"White matter alterations in early-stage alzheimer\u2019s disease: A tract-specific study","volume":"11","author":"Wen","year":"2019","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3389\/fnmol.2017.00206","article-title":"Increased white matter inflammation in aging- and alzheimer\u2019s disease brain","volume":"10","author":"Raj","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zigman, W.B. (2013). Atypical aging in down Syndrome. Developmental Disabilities Research Reviews, John Wiley and Sons Inc.","DOI":"10.1002\/ddrr.1128"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s11689-021-09366-1","article-title":"White matter microstructure associations with episodic memory in adults with Down syndrome: A tract-based spatial statistics study","volume":"13","author":"Bazydlo","year":"2021","journal-title":"J. Neurodev. Disord."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E1112","DOI":"10.21037\/jtd.2016.09.67","article-title":"When continuous positive airway pressure (CPAP) fails","volume":"8","author":"Virk","year":"2016","journal-title":"J. Thorac. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1155\/2008\/534372","article-title":"Long-term compliance with continuous positive airway pressure in patients with obstructive sleep apnea","volume":"15","author":"Wolkove","year":"2008","journal-title":"Can. Respir. J."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/10\/1322\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:09:41Z","timestamp":1760166581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/11\/10\/1322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,5]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["brainsci11101322"],"URL":"https:\/\/doi.org\/10.3390\/brainsci11101322","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,5]]}}}