{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:25:33Z","timestamp":1787041533668,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2145 SyNergy\u2014ID 390857198"],"award-info":[{"award-number":["EXC 2145 SyNergy\u2014ID 390857198"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG081394"],"award-info":[{"award-number":["R01 AG081394"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J intellect Disabil Res"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Down syndrome (DS) entails widespread age\u2010related functional decline affecting multiple organ systems, including genetically determined early\u2010onset Alzheimer disease (DSAD), resulting in an increased vulnerability to frailty early in life. We investigated the relationship between frailty, cognition and intellectual disability (ID) in adults with DS and explored biomarkers associated with frailty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This cross\u2010sectional study investigated 148 consecutive patients at a DSAD outpatient clinic. We applied correlation analyses and hierarchical linear models to determine associations of the Frailty Index for people with Intellectual Disabilities\u2014short form (ID\u2010FI\n                      <jats:sub>SF<\/jats:sub>\n                      ) with measures of cognition (Cambridge cognitive assessment, CAMCOG\u2010DS), adaptive function (short adaptive behaviour scale, SABS), motor function (SPES\/SCOPA), a screening tool (dementia screening questionnaire in individuals with intellectual disabilities, DSQIID\u2010G) for dementia\u2010related change in ADL (activities of daily living) performance, and ID severity (DSM\u20105). Patients were stratified as cognitively healthy, DS\u2010MCI, DSAD dementia, secondary cognitive decline (CD) or CD of unknown cause. Exploratory analyses included blood biomarkers, bioimpedance measurements and indirect calorimetry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both baseline ID severity (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.093,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014) and cognitive performance (CAMCOG\u2010DS,\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.0033,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) were independently associated with ID\u2010FI\n                      <jats:sub>SF<\/jats:sub>\n                      scores. Acquired cognitive decline was associated with (pre)frailty irrespective of aetiology. After adjustment for ID severity and cognition, ID\u2010FI\n                      <jats:sub>SF<\/jats:sub>\n                      scores were associated with adaptive function (SABS:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.0033,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), motor function (SPES\u2010SCOPA:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.015,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), change in ADL performance (DSQIID\u2010G:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.0061,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and medication burden (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.016,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Exploratory biomarker analyses identified associations with ID\u2010FI\n                      <jats:sub>SF<\/jats:sub>\n                      scores for markers of neurodegeneration, inflammation, body composition, cardiac function and cellular stress signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Frailty in DS is associated with both ID severity and acquired cognitive decline. Future studies should determine whether severe baseline ID increases susceptibility to frailty or primarily influences frailty measurement through lower baseline functional abilities, potentially necessitating ID\u2010adapted frailty thresholds. Biomarker associations further support a multifactorial model of frailty involving neurodegeneration, inflammation and sarcopenia\u2010related processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jir.70162","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:45:43Z","timestamp":1787039143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frailty in Adults With Down Syndrome: Cognitive, Functional and Biomarker Associations"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-7302","authenticated-orcid":false,"given":"Georg","family":"N\u00fcbling","sequence":"first","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9980-9981","authenticated-orcid":false,"given":"Lena","family":"Marth","sequence":"additional","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7117-2270","authenticated-orcid":false,"given":"Katja","family":"Sandk\u00fchler","sequence":"additional","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Stockbauer","sequence":"additional","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Wlasich","sequence":"additional","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5653-7737","authenticated-orcid":false,"given":"Alexander","family":"J\u00e4ck","sequence":"additional","affiliation":[{"name":"Department of Neurology, LMU University Hospital, LMU Medizin Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases  Munich 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