{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:31:25Z","timestamp":1792071085140,"version":"4.4.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Blood-based biomarkers identify Alzheimer disease and hold promise for monitoring disease progression, even in the preclinical disease stages.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate longitudinal trajectories of blood-based biomarkers and association with cognitive decline and risk of progression in individuals with subjective cognitive decline (SCD).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prospective cohort study (Subjective Cognitive Impairment Cohort) of individuals with SCD evaluated at a memory clinic underwent biennial biomarker collection and annual cognitive assessment and diagnostic evaluation from January 1, 2005, to December 31, 2023, with follow-up through 2023.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n Amyloid status was determined using positron emission tomography or cerebrospinal fluid. Plasma A\u03b2\n 42\/40<\/jats:sub>\n , phosphorylated tau 217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were measured biennially.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Cognitive trajectories in memory, attention, language, executive function, and global cognition and clinical progression to mild cognitive impairment or dementia.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 298 individuals (mean [SD] age, 61.55 [8.08] years; 174 [58.4%] male) with SCD were included, of whom 80 were amyloid-positive (A+) and 218 were amyloid-negative (A\u2212). Mean (SD) follow-up was 4.8 (2.6) years. Individuals with SCD A+ were older (mean [SD] age, 65.25 [7.14] years; 42 [52.5%] male) than those with SCD A\u2212 (mean [SD] age, 60.19 [8.00] years; 132 [60.6%] male). For pTau217, GFAP, and NfL, baseline levels were higher in the A+ group compared with A\u2212 group (estimates [SE] amyloid \u03b2, 1.11 [0.11], 0.69 [0.13], and 0.36 [0.10], respectively;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001 for all). Additionally, these biomarkers showed steeper increases over time in the A+ group than in A\u2212 group (estimates [SE] time\u2009\u00d7\u2009amyloid status \u03b2, 0.07 [0.02],\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; 0.07 [0.02],\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001; and 0.05 [0.02],\n P<\/jats:italic>\n \u2009=\u2009.005, respectively). Longitudinal increases in pTau217 and GFAP were associated with cognitive decline over time in all domains (\u03b2 time\u2009\u00d7\u2009biomarker slope\u2009=\u2009\u22120.02 to \u22120.04). Longitudinal decreases in A\u03b2\n 42\/40<\/jats:sub>\n and increases in NfL were associated with cognitive decline in global cognition (\u03b2 = 0.03 [0.01],\n P<\/jats:italic>\n \u2009=\u2009.04) and language (\u03b2\u2009=\u20090.04 [0.02],\n P<\/jats:italic>\n \u2009=\u2009.03), and increases in NfL were also associated with decline in global cognition (\u03b2\u2009=\u2009\u22120.02 [0.01],\n P<\/jats:italic>\n \u2009=\u2009.004), language (\u03b2\u2009=\u2009\u22120.03 [0.01],\n P<\/jats:italic>\n \u2009=\u2009.007), and executive functioning (\u03b2\u2009=\u2009\u22120.03 [0.01],\n P<\/jats:italic>\n \u2009=\u2009.02). Steeper pTau217 slope was associated with progression from SCD to mild cognitive impairment or dementia (hazard ratio [HR], 3.6; 95% CI, 1.8-7.4 per 0.05 SD increase per year; C index, 0.89; 95% CI, 0.84-0.93), as were steeper GFAP slope (HR, 1.5 [95% CI, 1.0-2.2]; C index, 0.81 [95% CI, 0.73-0.88]) and steeper NfL slope (HR, 2.6 [95% CI, 1.3-5.2]; C index, 0.77 [95% CI, 0.69-0.85]). A\u03b2\n 42\/40<\/jats:sub>\n slope was not associated with progression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study of individuals with SCD suggests that longitudinal plasma pTau217 and GFAP are suitable biomarkers for monitoring AD pathology. Their changes were associated with cognitive decline and clinical progression, supporting their potential utility for early intervention and disease monitoring.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.45862","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T16:00:26Z","timestamp":1764777626000},"page":"e2545862","source":"Crossref","is-referenced-by-count":18,"title":["Longitudinal Blood-Based Biomarkers and Clinical Progression in Subjective Cognitive Decline"],"prefix":"10.1001","volume":"8","author":[{"given":"Calvin","family":"Trieu","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"},{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam, Netherlands"},{"name":"Faculty of Behavioural and Movement Sciences, Department of Clinical, Neuro and Developmental Psychology & Clinical Neuropsychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argonde C.","family":"van Harten","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mardou S. 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A.","family":"van Leeuwenstijn","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Marie","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Boonkamp","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azzam","family":"Aladdin","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sietske A. M.","family":"Sikkes","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"},{"name":"Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands"},{"name":"Faculty of Behavioural and Movement Sciences, Department of Clinical, Neuro and Developmental Psychology & Clinical Neuropsychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsmarieke","family":"van de Giessen","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge M. 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