{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:44:44Z","timestamp":1771922684978,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"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. Neurol."],"abstract":"<jats:p>Down syndrome (DS) occurs in approximately one in 800 births worldwide and is associated with various medical complications including swallowing impairments and dysphagia. Advances in childhood survival have led to an increased number of people with DS reaching older ages. Aging is generally accompanied by changes in sensory and motor functions, including those involved in swallowing. Swallowing impairments can lead to complications such as malnutrition, dehydration, and aspiration pneumonia. Despite the multifactorial nature of swallowing impairments in older people with DS, research in this area remains limited, with most studies focusing on pediatric populations. We hypothesized that aged Ts65Dn mice (mouse model of DS; 14 males, 15 females) would demonstrate significant impairments in swallowing performance on quantitative measures derived from videofluoroscopic swallow studies, relative to age-matched euploid controls (genetically typical mice; 14 males and 15 females). Statistical analyses included two-way ANOVA for genotype and sex effects. The Ts65Dn group exhibited significantly lower swallow rates, longer inter-swallow intervals (ISI), increased jaw cycle: swallow ratios (JSR), and lower jaw excursion rates (JER) than euploid controls. Body weight was significantly lower in the Ts65Dn group. These findings confirm persistent swallowing impairments in aged Ts65Dn mice, supporting their use as a model for studying swallowing mechanisms, provide critical insights into swallowing impairments in aging DS and support the need for specialized clinical interventions for swallowing disorders in this population.<\/jats:p>","DOI":"10.3389\/fneur.2026.1703041","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:36:34Z","timestamp":1768973794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Swallowing characteristics in Down syndrome at an advanced age: a preclinical study in the Ts65Dn mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Marziyeh","family":"Ostadi","sequence":"first","affiliation":[{"name":"Department of Communication Sciences and Disorders, University of Wisconsin","place":["Madison, WI, United States"]},{"name":"Department of Otolaryngology, Head and Neck Surgery, University of Wisconsin","place":["Madison, WI, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin H.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, University of Wisconsin","place":["Madison, WI, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y. Eugene","family":"Yu","sequence":"additional","affiliation":[{"name":"The Children\u2019s Guild Foundation Down Syndrome Research Program, Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center","place":["Buffalo, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine P.","family":"Connor","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders, University of Wisconsin","place":["Madison, WI, United States"]},{"name":"Department of Otolaryngology, Head and Neck Surgery, University of Wisconsin","place":["Madison, WI, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany J.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, University of Wisconsin","place":["Madison, WI, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nrg1448","article-title":"Chromosome 21 and down syndrome: from genomics to pathophysiology","volume":"5","author":"Antonarakis","year":"2004","journal-title":"Nat Rev Genet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"86","DOI":"10.17294\/2330-0698.1824","article-title":"Prevalence of common disease conditions in a large cohort of individuals with down syndrome in the United States","volume":"8","author":"Chicoine","year":"2021","journal-title":"J Patient Cent Res Rev"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1056\/nejmra1706537","article-title":"Down syndrome","volume":"382","author":"Bull","year":"2020","journal-title":"N Engl J Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e2301","DOI":"10.1002\/bdr2.2301","article-title":"National population-based estimates for major birth defects, 2016\u20132020","volume":"116","author":"Stallings","year":"2024","journal-title":"Birth Defects Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/gim.2016.127","article-title":"Estimation of the number of people with down syndrome in the United States","volume":"19","author":"De Graaf","year":"2017","journal-title":"Genet Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1001\/jamaneurol.2018.2210","article-title":"Prevalence of aging, dementia, and multimorbidity in older adults with down syndrome","volume":"75","author":"Bayen","year":"2018","journal-title":"JAMA Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"153","DOI":"10.21926\/obm.geriatr.2101153","article-title":"Which physiological swallowing parameters change with healthy aging?","volume":"5","author":"Mancopes","year":"2021","journal-title":"OBM Geriatr"},{"key":"ref8","first-page":"488","volume-title":"Dysphagia in older adults","author":"Thiyagalingam","year":"2021"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s00455-007-9096-1","article-title":"The impact of aging on eating, drinking, and swallowing function in people with down\u2019s syndrome","volume":"23","author":"Lazenby","year":"2008","journal-title":"Dysphagia"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1007\/s00455-016-9695-9","article-title":"A systematic review of the prevalence of oropharyngeal dysphagia in stroke, Parkinson\u2019s disease, Alzheimer\u2019s disease, head injury, and pneumonia","volume":"31","author":"Takizawa","year":"2016","journal-title":"Dysphagia"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s10882-022-09875-4","article-title":"Swallowing related problems of toddlers with down syndrome","volume":"35","author":"Serel Arslan","year":"2023","journal-title":"J Dev Phys Disabil"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1111\/jir.12617","article-title":"Feeding and swallowing difficulties in children with down syndrome","volume":"63","author":"Anil","year":"2019","journal-title":"J Intellect Disabil Res"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1177\/0194599813483445","article-title":"Pharyngeal dysphagia in children with down syndrome","volume":"149","author":"O\u2019Neill","year":"2013","journal-title":"Otolaryngol Head Neck Surg"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"847","DOI":"10.3390\/children11070847","article-title":"Assessment and rehabilitation intervention of feeding and swallowing skills in children with down syndrome using the global intensive feeding therapy (GIFT)","volume":"11","author":"Franceschetti","year":"2024","journal-title":"Children (Basel)"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.respol.2015.11.009","article-title":"Evaluating research: a multidisciplinary approach to assessing research practice and quality","volume":"45","author":"M\u00e5rtensson","year":"2016","journal-title":"Res Policy"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"472","DOI":"10.3109\/17483107.2012.746398","article-title":"A qualitative study of adult AAC users\u2019 experiences communicating with medical providers","volume":"8","author":"Morris","year":"2013","journal-title":"Disabil Rehabil Assist Technol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.2522\/ptj.20060334","article-title":"Aging and down syndrome: implications for physical therapy","volume":"87","author":"Barnhart","year":"2007","journal-title":"Phys Ther"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"54071","DOI":"10.1155\/2012\/584071","article-title":"Mouse models of down syndrome as a tool to unravel the causes of mental disabilities","volume":"2012","author":"Rueda","year":"2012","journal-title":"Neural Plast"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s00455-016-9778-7","article-title":"Animal models for dysphagia studies: what have we learnt so far","volume":"32","author":"German","year":"2017","journal-title":"Dysphagia"},{"key":"ref20","first-page":"117","article-title":"Segmental trisomy as a mouse model for down syndrome","volume":"384","author":"Davisson","year":"1993","journal-title":"Prog Clin Biol Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"R1251","DOI":"10.1152\/ajpregu.00312.2012","article-title":"Functional and biochemical characterization of soleus muscle in down syndrome mice: insight into the muscle dysfunction seen in the human condition","volume":"303","author":"Cowley","year":"2012","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"134569","DOI":"10.1016\/j.neulet.2019.134569","article-title":"Neurodevelopmental wiring deficits in the Ts65Dn mouse model of down syndrome","volume":"714","author":"Jain","year":"2020","journal-title":"Neurosci Lett"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"113390","DOI":"10.1016\/j.physbeh.2021.113390","article-title":"Masticatory function in children with down syndrome","volume":"235","author":"Wintergerst","year":"2021","journal-title":"Physiol Behav"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1384572","DOI":"10.3389\/fneur.2024.1384572","article-title":"Altered tongue muscle contractile properties coincide with altered swallow function in the adult Ts65Dn mouse model of down syndrome","volume":"15","author":"Glass","year":"2024","journal-title":"Front Neurol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"906","DOI":"10.3389\/fnins.2019.00906","article-title":"The adult Ts65Dn mouse model of down syndrome shows altered swallow function","volume":"13","author":"Glass","year":"2019","journal-title":"Front Neurosci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1590\/s0004-28032010000400001","article-title":"Videofluoroscopy: the gold standard exam for studying swallowing and its dysfunction","volume":"47","author":"Costa","year":"2010","journal-title":"Arq Gastroenterol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e52319","DOI":"10.3791\/52319","article-title":"Adapting human videofluoroscopic swallow study methods to detect and characterize dysphagia in murine disease models","volume":"97","author":"Lever","year":"2015","journal-title":"JoVE"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1007\/s00455-015-9604-7","article-title":"Videofluoroscopic validation of a translational murine model of presbyphagia","volume":"30","author":"Lever","year":"2015","journal-title":"Dysphagia"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1007\/s00455-020-10242-8","article-title":"The influence of age, eating a meal, and systematic fatigue on swallowing and mealtime parameters","volume":"36","author":"Brates","year":"2021","journal-title":"Dysphagia"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3390\/geriatrics3040069","article-title":"Age-related changes to eating and swallowing impact frailty: aspiration, choking risk, modified food texture and autonomy of choice","volume":"3","author":"Cichero","year":"2018","journal-title":"Geriatrics"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"260","DOI":"10.3389\/fphys.2012.00260","article-title":"Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review","volume":"3","author":"Mitchell","year":"2012","journal-title":"Front Physiol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s12603-018-1029-1","article-title":"Influence of age and tooth loss on masticatory muscles characteristics: a population based MR imaging study","volume":"22","author":"Daboul","year":"2018","journal-title":"J Nutr Health Aging"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/ggi.13591","article-title":"Sarcopenia and dysphagia: position paper by four professional organizations","volume":"19","author":"Fujishima","year":"2019","journal-title":"Geriatr Gerontol Int"},{"key":"ref34","first-page":"635","volume-title":"Down syndrome, accelerated aging and immunosenescence","author":"Gensous","year":"2020"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.physbeh.2004.04.003","article-title":"Licking rate adaptations to increased mandibular weight in the adult rat","volume":"82","author":"Carvalho","year":"2004","journal-title":"Physiol Behav"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.physbeh.2007.12.010","article-title":"Effect of occlusal appliance wear on chewing in persons with down syndrome","volume":"93","author":"Mazille","year":"2008","journal-title":"Physiol Behav"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1152\/jn.01122.2003","article-title":"Influence of age on adaptability of human mastication","volume":"92","author":"Peyron","year":"2004","journal-title":"J Neurophysiol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2008.03.008","article-title":"Towards developing standard operating procedures for pre-clinical testing in the mdx mouse model of Duchenne muscular dystrophy","volume":"31","author":"Grounds","year":"2008","journal-title":"Neurobiol Dis"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1002\/ddrr.1128","article-title":"Atypical aging in down syndrome","volume":"18","author":"Zigman","year":"2013","journal-title":"Dev Disabil Res Rev"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.3233\/JAD-220865","article-title":"Weight loss and Alzheimer\u2019s disease in down syndrome","volume":"91","author":"Fleming","year":"2023","journal-title":"J Alzheimer's Dis"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1123\/apaq.2020-0004","article-title":"Age-group differences in body mass index, weight, and height in adults with down syndrome and adults with intellectual disability from the United States","volume":"38","author":"Agiovlasitis","year":"2020","journal-title":"Adapt Phys Act Q"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1093\/hmg\/ddad056","article-title":"Dissection of a down syndrome-associated trisomy to separate the gene dosage-dependent and-independent effects of an extra chromosome","volume":"32","author":"Xing","year":"2023","journal-title":"Hum Mol Genet"},{"key":"ref43","first-page":"1","volume-title":"Mouse models of down syndrome. Genetic models of down syndrome","author":"Folz","year":"2025"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1038\/s41431-018-0172-9","article-title":"The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports","volume":"26","author":"Engwerda","year":"2018","journal-title":"Eur J Hum Genet"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1703041\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:39:34Z","timestamp":1771918774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1703041\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":44,"alternative-id":["10.3389\/fneur.2026.1703041"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1703041","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"article-number":"1703041"}}