{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:23:53Z","timestamp":1788971033768,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01\u2010AG082052"],"award-info":[{"award-number":["R01\u2010AG082052"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P50 AG033514"],"award-info":[{"award-number":["P50 AG033514"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG027161"],"award-info":[{"award-number":["R01 AG027161"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG021155"],"award-info":[{"award-number":["R01 AG021155"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2023\u20100035"],"award-info":[{"award-number":["#2023\u20100035"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2022\u201001018"],"award-info":[{"award-number":["#2022\u201001018"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2019\u201002397"],"award-info":[{"award-number":["#2019\u201002397"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>While language deficits are among the earliest detectable signs of Alzheimer`s disease (AD), no existing composites integrate connected speech \u2013 essential for capturing real\u2010world communication \u2013 limiting precise detection and personalized interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed cohort data from 824 non\u2010demented adults and constructed three language composites: a theoretical composite based on expert knowledge, a connected speech\u2010specific composite derived from the theoretical composite, and an empirical language composite optimized for predicting cognitive progression. We compared their longitudinal sensitivity to plasma tau phosphorylated at threonine 217 (p\u2010tau217), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The empirical language composite showed superior and consistent sensitivity (faster decline rate) with all three biomarkers. Proper name recall declined uniquely with increased p\u2010tau217, while animal fluency declined selectively with higher NfL and GFAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>An empirical language composite captures holistic cognitive\u2010communicative decline, while individual measures may imply a biomarker\u2010specific language profile. Our findings support the clinical utility of plasma biomarkers and\u00a0language\u2010specific\u00a0composites as sensitive early indicators of disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Empirical language composite had optimal sensitivity to plasma p\u2010tau217, NfL, GFAP.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>It comprises words\/minute, filled pauses, proper name recall, and animal fluency.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>It offers potential for language\u2010dominant ADRD precise detection and monitoring.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70975","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:16:44Z","timestamp":1765343804000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development of language composites for enhanced sensitivity to multiple plasma biomarkers"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-6871","authenticated-orcid":false,"given":"Deling","family":"He","sequence":"first","affiliation":[{"name":"Department of Communication Sciences and Disorders University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E","family":"Langhough","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Van Hulle","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Basche","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Jonaitis","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Wilson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine and Public Health University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  Gothenburg Sweden"},{"name":"Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Department of Neurodegenerative Disease, Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling","family":"Johnson","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly D.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Communication Sciences and Disorders University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Disease Research Center University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Institute University of Wisconsin\u2013Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/02687038.2019.1608502"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt269"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160252"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.070753"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12072"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.803"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.12.009"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1590\/s1980\u201057642014dn83000016"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.04.011"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1352822"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2017.10.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2015.11.003"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.087520"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102017\u2010317260"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023620\u2010z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01474-z"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab223"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13829"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/arclin\/acw024"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355682"},{"key":"e_1_2_8_24_1","first-page":"688478","volume-title":"Validity Evidence for the Research Category, \u201cCognitively Unimpaired \u2013 Declining,\u201d as a Risk Marker for Mild Cognitive Impairment and Alzheimer's Disease","author":"Langhough Koscik R","year":"2021"},{"key":"e_1_2_8_25_1","volume-title":"Boston diagnostic aphasia examination booklet","author":"Goodglass H","year":"1983"},{"key":"e_1_2_8_26_1","volume-title":"Wechsler memory scale\u2010revised","author":"Wechsler D","year":"1987"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1044\/2023_AJSLP-23-00217"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12294"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00437"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12203"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2020.07.008"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2023.09.018"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.5319"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.6117"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14215"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab335"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12203"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12331"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12761"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001249\u20100"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.5017"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023620\u2010z"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010022\u201001093\u20106"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2016.12.001"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13774"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/13803395.2018.1446513"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.09.029"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad042"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70975","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70975","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T03:41:33Z","timestamp":1780285293000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":47,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/alz.70975"],"URL":"https:\/\/doi.org\/10.1002\/alz.70975","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70975"}}