Evidence map›Paper›PMID 42092335›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Associations of blood biomarkers of glial cell dysfunction and neuronal injury with future cognitive decline and incident dementia.

Srishti Shrestha, Xiaoqian Zhu, B Gwen Windham, Kevin J Sullivan, Priya Palta, Rebecca F Gottesman, Russell P Tracy, Clifford R Jack, Petrice M Cogswell, Prashanthi Vemuri and 4 more

Abstract read
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Srishti ShresthaThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Xiaoqian ZhuThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
B Gwen WindhamThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Kevin J SullivanThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Priya PaltaDepartment of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Rebecca F GottesmanStroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, Bethesda, Maryland, USA.
Russell P TracyDepartment of Pathology and Laboratory Medicine and Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Petrice M CogswellDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Prashanthi VemuriDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Sudha SeshadriGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas, USA.
Thomas H MosleyThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Michael E GriswoldThe Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Myriam FornageThe Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.

Funding

ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
The Clinical Significance of Incidental White Matter Lesions on MRI Amongst a Diverse Population with Cognitive Complaints (INDEED)U19NS120384 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DAVID K JOHNSON · 2020 to 2026
$61.9M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5U01HL096917 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI MOSLEY, THOMAS H · 2010 to 2018
$11.9M
ARIC Neurocognitive Study (ARIC-NCS) Renewal UNC 4 of 5U01HL096899 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID J · 2010 to 2018
$7.5M
ARIC Neurocognitive Study (ARIC-NCS)U01HL096902 · NHLBI · UNIVERSITY OF MINNESOTA · PI LUTSEY, PAMELA L. · 2010 to 2018
$7.4M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 4 of 5U01HL096814 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HUGHES, TIMOTHY M., WAGENKNECHT, LYNNE E · 2010 to 2018
$6.5M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00003 · NHLBI · UNIVERSITY OF MINNESOTA · PI LUTSEY, PAMELA · 2022 to 2025
$5.1M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WAGENKNECHT, LYNNE · 2022 to 2025
$5.0M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00004 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI WINDHAM, BEVERLY GWEN · 2022 to 2025
$4.8M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00002 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CORESH, JOSEF · 2022 to 2025
$4.7M
Multiethnic Validation of VCID Biomarkers in South TexasU01NS125513 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FORNAGE, MYRIAM, SATIZABAL, CLAUDIA L · 2023 to 2025
$3.3M
NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NIA NIH HHS R00 AG052830NIA NIH HHS R00AG052830NIH HHS andUF1NS125513NIH HHS U01HL096812NIH HHS U01HL096814NIH HHS U01HL096899NIH HHS U01HL096902NIH HHS U01HL096917NIH HHS U19NS120384NIH HHS UH3NS100605NINDS NIH HHS Intramural Research ProgramNINDS NIH HHS U01 NS125513NINDS NIH HHS U19 NS120384NINDS NIH HHS UF1 NS125513NINDS NIH HHS UH2 NS100605NINDS NIH HHS UH3 NS100605
6 · The paper itself

Abstract

introductionProspective studies of blood-based biomarkers reflecting pathogenic processes, other than Alzheimer-specific pathologies, that contribute to dementia in diverse cohorts are lacking.

methodsWe 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.

resultsHigher 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.

Indexed as

BiomarkersCognitive DysfunctionDementiaNeurogliaNeuronsAgedChitinase-3-Like Protein 1FemaleGlial Fibrillary Acidic ProteinHumansIncidenceLipopolysaccharide ReceptorsMaleMiddle AgedNeurofilament ProteinsProspective StudiesBiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1GFAP protein, humanGlial Fibrillary Acidic ProteinLipopolysaccharide ReceptorsNeurofilament Proteinstau ProteinsUbiquitin ThiolesteraseUCHL1 protein, humanARIC studyblood‐based biomarkerschitinase‐3‐like protein 1cognitive declineGFAPglial fibrillary acidic proteinincident dementianeurofilament light chainNfLsCD14soluble cluster of differentiation‐14ubiquitin C‐terminal hydrolase L1UCHL1YKL‐40

Identifiers

PMID42092335
PMCPMC13149226

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.