{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:16:15Z","timestamp":1770750975987,"version":"3.50.0"},"reference-count":0,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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"}],"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>Plasma biomarkers have demonstrated excellent performances in detecting AD\/ADRD\u2010related brain pathology. However, their relationship with cognitive decline remains unclear. We examined this in a large memory clinic cohort with baseline plasma biomarkers and repeated cognitive assessments over approximately three decades.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Participants at the University of Pittsburgh Alzheimer's Disease Research Center underwent blood collection and Clinical Dementia Rating (CDR) Sum of Boxes\u2010based cognitive assessment cross\u2010sectionally, followed by annual CDR assessments for up to 29 years (3.0 [IQR 1.9\u20105.9]). Plasma\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau181,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau217, brain\u2010derived tau (BD\u2010tau), GFAP and NfL, were measured using SIMOA assays. Linear\/logistic regression and Fisher's exact were employed for statistical inference.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      We included 4,073 participants (59.9% female; 90.2% self\u2010identified non\u2010Hispanic White), aged 71.9 \u00b1 9.8 years, with 2160 being non\u2010demented (CDR\u22640.5) at baseline. Cross\u2010sectionally, higher levels of all biomarkers were significantly associated with worse CDR scores. Longitudinally, baseline\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau181 and GFAP levels best predicted cognitive decline at 0\u20102, 2\u20105, 5\u201010, and &gt;10 years. In contrast,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau217 was superior at predicting whether cognitive decline would happen at all within 2, 5, or 10 years, with AUCs up to 0.810. Participants with above\u2010median\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau217 levels had the highest odds of cognitive decline (2.57, 4.53, and 10.34 times within 2, 5 and 10 years, respectively).\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau217, and\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau217\/BD\u2010tau ratio accounting for CNS\u2010derived\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau217, were most effective in predicting cognitive decline in participants who were cognitively non\u2010demented at baseline. Importantly, cognitively stable individuals had lower levels of all plasma biomarkers vs. progressors, with\n                      <jats:italic>p<\/jats:italic>\n                      \u2010tau217 best at separating these groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Leveraging a large cohort with extensive longitudinal data, our findings underscore the significant value of blood\u2010based biomarkers in predicting cognitive decline to aid personalized clinical management and ultimately improve patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz70856_106702","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T22:31:43Z","timestamp":1768429903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma biomarkers predict incident cognitive decline up to 29 years prior to disease onset: a memory clinic cohort study of 4,073 participants"],"prefix":"10.1002","volume":"21","author":[{"given":"Xuemei","family":"Zeng","sequence":"first","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca A","family":"Deek","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel N","family":"Nafash","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy M.","family":"Gu","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamia","family":"Choity","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara K","family":"Lafferty","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa F","family":"Farinas","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret A","family":"Bedison","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocco B","family":"Mercurio","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Alzheimer's Disease Research Center (ADRC), Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristy","family":"Matan","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Gogola","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia K.","family":"Kofler","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana L","family":"Tudorascu","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Elizabeth","family":"Shaaban","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer H","family":"Lingler","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Alzheimer's Disease Research Center (ADRC), Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tharick A","family":"Pascoal","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E","family":"Klunk","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Alzheimer's Disease Research Center (ADRC), Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor L.","family":"Villemagne","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milos D.","family":"Ikonomovic","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah B","family":"Berman","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sweet","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth E.","family":"Snitz","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann D","family":"Cohen","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Alzheimer's Disease Research Center (ADRC), Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Ilyas","family":"Kamboh","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Alzheimer's Disease Research Center (ADRC), Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar L","family":"Lopez","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Alzheimer's Disease Research Center (ADRC), Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas K","family":"Karikari","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz70856_106702","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz70856_106702","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:13:09Z","timestamp":1770721989000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz70856_106702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":0,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/alz70856_106702"],"URL":"https:\/\/doi.org\/10.1002\/alz70856_106702","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":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e106702"}}