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Using translational mouse models, we investigated sleep disturbances and inflammation associated with normal aging, TBI and aging, and AD. We hypothesized that aging results in marked changes in sleep compared with adult mice, and that TBI and aging would result in sleep and inflammation levels similar to AD mice. We used female 16\u2010month\u2010old wild\u2010type (WT Aged) and 3xTg\u2010AD mice, as well as a 2\u2010month\u2010old reference group (WT Adult), to evaluate sleep changes. WT Aged mice received diffuse TBI by midline fluid percussion, and blood was collected from both WT Aged (pre\u2010 and post\u2010TBI) and 3xTg\u2010AD mice to evaluate inflammation. Cognitive behavior was tested, and tissue was collected for histology. Bayesian generalized additive and mixed\u2010effects models were used for analyses. Both normal aging and AD led to increases in sleep compared with adult mice. WT Aged mice with TBI slept substantially more, with fragmented shorter bouts, than they did pre\u2010TBI and compared with AD mice. However, differences between WT Aged and 3xTg\u2010AD mice in immune cell populations and plasma cytokine levels were incongruous, cognitive deficits were similar, and cumulative sleep was not predictive of inflammation or behavior for either group. Our results suggest that in similarly aged individuals, TBI immediately induces more profound sleep alterations than in AD, although both diseases likely include cognitive impairments. Unique pathological sleep pathways may exist in elderly individuals who incur TBI compared with similarly aged individuals who have AD, which may warrant disease\u2010specific treatments in clinical settings.<\/jats:p>","DOI":"10.1002\/jnr.24771","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T13:03:06Z","timestamp":1608037386000},"page":"1136-1160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease\u2010specific changes in sleep and incongruous peripheral inflammation"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-3993","authenticated-orcid":false,"given":"Maha","family":"Saber","sequence":"first","affiliation":[{"name":"BARROW Neurological Institute at Phoenix Children's Hospital Phoenix AZ USA"},{"name":"Department of Child Health University of Arizona College of Medicine\u2014Phoenix Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9404-8878","authenticated-orcid":false,"given":"Sean M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Child Health University of Arizona College of Medicine\u2014Phoenix Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerin","family":"Cho","sequence":"additional","affiliation":[{"name":"BARROW Neurological Institute at Phoenix Children's Hospital Phoenix AZ USA"},{"name":"Department of Child Health University of Arizona College of Medicine\u2014Phoenix Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Lifshitz","sequence":"additional","affiliation":[{"name":"BARROW Neurological Institute at Phoenix Children's Hospital Phoenix AZ USA"},{"name":"Department of Child Health University of Arizona College of Medicine\u2014Phoenix Phoenix AZ USA"},{"name":"Phoenix Veteran Affairs Health Care System Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-3159","authenticated-orcid":false,"given":"Rachel K.","family":"Rowe","sequence":"additional","affiliation":[{"name":"BARROW Neurological Institute at Phoenix Children's Hospital Phoenix AZ USA"},{"name":"Department of Child Health University of Arizona College of Medicine\u2014Phoenix Phoenix AZ USA"},{"name":"Phoenix Veteran Affairs Health Care System Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-015-0228-5"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3648"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00124-X"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1991.tb01647.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858402008003013"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-012-9164-5"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-012-8178-x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm109"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12873"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3181ba3354"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/pan\/mpi014"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0171-4"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v080.i01"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.32614\/RJ-2018-017"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3475"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v076.i01"},{"key":"e_1_2_12_18_1","volume-title":"Regression analysis with R: Design and develop statistical nodes to identify unique relationships within data at scale","author":"Ciaburro G.","year":"2018"},{"key":"e_1_2_12_19_1","volume-title":"Statistical power analysis for the behavioral sciences","author":"Cohen J.","year":"1988"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00695"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-925X-7-14"},{"key":"e_1_2_12_22_1","first-page":"273","article-title":"Treatment of sleeping disorders should be considered in clinical management of Parkinson's disease","volume":"6","author":"Santos A. 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