Associations of blood biomarkers of glial cell dysfunction and neuronal injury with future cognitive decline and incident dementia
Year: 2026
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Prospective studies of blood-based biomarkers reflecting pathogenic processes, other than Alzheimer-specific pathologies, that contribute to dementia in diverse cohorts are lacking. METHODS: We jointly fitted linear mixed-effect models and proportional hazards models to examine associations of midlife glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL-40), soluble cluster of differentiation-14 (sCD14), neurofilament light chain (NfL), total tau (t-tau), and ubiquitin C-terminal hydrolase L1 (UCHL1) levels in serum (collected in 1993 to 1995) with cognitive decline and incident dementia (ascertained over 29 years through 2022) in the community-based Atherosclerosis Risk in Communities Study. sCD14 and YKL-40 were measured in 3082 participants and the other four biomarkers in 1766 participants. RESULTS: Higher serum GFAP, YKL-40, sCD14, and NfL were associated with faster cognitive decline and elevated dementia rate (e.g., 1 standard deviation [SD] higher log-base2 YKL-40 was associated with -0.11SD faster 25-year cognitive decline (95% confidence interval [CI]: -0.15,-0.07) and 45% higher dementia hazard (hazard ratio [HR]: 1.45 [95% CI: 1.25, 1.68]). Higher t-tau and UCHL1 were also associated with faster cognitive decline. DISCUSSION: Midlife blood biomarkers reflecting glial and neuronal dysfunction and neuroinflammation are associated with early cognitive impairment.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71422
Institutions: University of Mississippi Medical Center, University of North Carolina at Chapel Hill, National Institute of Neurological Disorders and Stroke, University of Vermont, Mayo Clinic, The University of Texas at San Antonio Health Science Center, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Awards: G1194882026, G124418500, G1518371162, ARIC Neurocognitive Study (ARIC-NCS) Renewal, G1623886336, G1632931450, G17707931, G1773517813, G1924893021, G2103396735, Microglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE Consortium, G2195207551, G2287024733, G2339050794, G2883369658, G2889674361, G2991237628, Physical Activity and Preservation of Cognitive Function, G351949366, G354227350, G3931319179, G3938966547, G3978702139, G421917476, G4397751285, G456869620, ARIC Neurocognitive Study (ARIC-NCS) Renewal UNC 4 of 5, G4782323294, G4819198047, G4846232932, G4961862235, ARIC Neurocognitive Study (ARIC-NCS) Renewal 4 of 5, G5104152550, G5267790454, G5364873420, G54938809, G557577377, G5792112273, G583528397, G5954722477, G6146435619, G6265038979, G6281193135, G6418484092, ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5, ARIC Neurocognitive Study (ARIC-NCS), G6811927220, Multiethnic Validation of VCID biomarkers in South Texas, G6978868085, G7177917790, G7243995979, G7276788223, G748486544, G7491785057, G8008717573, G8773483559, G8946053683, G9000005794, G9000028535, G9000076324, G9000079369, G9000100377, G9000182244, G9000344661, Multiethnic Validation of VCID Biomarkers in South Texas, The Clinical Significance of Incidental White Matter Lesions on MRI Amongst a Diverse Population with Cognitive Complaints (INDEED)
OpenAlex ID: W7160419274