{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:01:47Z","timestamp":1789999307091,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2026,1]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Escitalopram for Agitation in Alzheimer's Disease (S\u2010CitAD) is a National Institutes of Health\u2013funded randomized controlled trial that randomized 173 participants with clinically diagnosed Alzheimer's disease (AD) and agitation to escitalopram or placebo for 12 weeks, assessing efficacy and safety. There was no advantage for escitalopram in treating agitation, potentially attributed to including participants at various stages of AD brain pathology, reflected in levels of blood biomarkers. Here, we (1) estimated the fraction of participants meeting blood biomarker criteria for AD pathology, (2) examined associations between baseline blood biomarkers and agitation severity or cognitive functioning, and (3) evaluated whether baseline blood biomarkers predicted treatment response.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Eighty\u2010two randomized participants provided blood for biomarker measurement prior to randomization. Plasma amyloid beta (A\u03b2)42, A\u03b240, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau (p\u2010tau)217 were measured using standard methods. We examined associations of baseline blood biomarkers and clinical measures at baseline and follow\u2010up with (1) agitation severity (Neuropsychiatric Inventory Clinical Rating of the agitation and aggression domains [NPI\u2010C\u2010A+A]), (2) cognitive status (Mini\u2010Mental State Examination [MMSE]), and (3) escitalopram treatment.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Seventy\u2010seven out of 82 (94%) scored above threshold for p\u2010tau217, supporting the clinical diagnosis of AD. Baseline higher p\u2010tau217 predicted higher NPI\u2010C\u2010A+A scores at weeks 6 (beta = 3.26,\n p<\/jats:italic>\n < 0.001) and 12 (beta = 2.86,\n p<\/jats:italic>\n = 0.01) after randomization. Baseline higher levels of GFAP (beta = \u22120.02,\n p<\/jats:italic>\n = 0.0002) and p\u2010tau217 (beta = \u22122.68,\n p<\/jats:italic>\n = 0.003) were associated with lower baseline MMSE scores. After adjusting for treatment, higher baseline p\u2010tau217 was associated with greater odds of worsening NPI\u2010C\u2010A+A scores at weeks 6 (odds ratio [OR] = 2.79,\n p<\/jats:italic>\n = 0.02) and 12 (OR = 2.55,\n p<\/jats:italic>\n = 0.02).\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n In this clinical trial cohort, elevated plasma p\u2010tau217 confirmed AD pathology in 94% of participants and forecast greater agitation severity and worse cognitive functioning, underscoring its practical value for stratifying and monitoring patients in neuropsychiatric intervention studies.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n We examined whether Alzheimer's disease (AD) blood biomarkers predicted severity of agitation and cognitive impairment and\/or treatment response in the 12\u2010week Escitalopram for Agitation in Alzheimer's Disease (S\u2010CitAD) randomized controlled trial.<\/jats:p>\n <\/jats:list-item>\n \n Blood phosphorylated tau (p\u2010tau)217 confirmed the presence of significant AD brain amyloid pathology in 94% of these clinically diagnosed participants.<\/jats:p>\n <\/jats:list-item>\n \n Independent of treatment assignment, higher baseline p\u2010tau217 predicted lower baseline and future Mini\u2010Mental State Examination (MMSE) scores and worse agitation overtime.<\/jats:p>\n <\/jats:list-item>\n \n Independent of treatment assignment, higher baseline levels of glial fibrillary acidic protein were associated with lower baseline and follow\u2010up MMSE scores.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/trc2.70203","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:15:03Z","timestamp":1768799703000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Blood biomarkers for Alzheimer's disease are correlated with measures of agitation and cognition in a randomized trial assessing the effects of escitalopram on agitation"],"prefix":"10.1002","volume":"12","author":[{"given":"Maansi","family":"Barnwal","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheriza","family":"Baksh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahinoor","family":"Ismail","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Clinical Neurosciences, Community Health Sciences, and Pathology & Laboratory Medicine, Hotchkiss Brain Institute and O'Brien Institute for Public Health University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Shade","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay","family":"Moghekar","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara G.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton P.","family":"Porsteinsson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Rochester School of Medicine and Dentistry Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine G.","family":"Lyketsos","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the S\u2010CitAD Research 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