Evidence map›Paper›PMID 40785309›Full record

ArticleJournal of Alzheimer's disease : JAD2025

The relationships between cerebrospinal fluid neurofilament light chain and hippocampal atrophy with cognitive decline.

Ramkrishna K Singh, Semere Bekena, Nikitha Damera, Yiqi Zhu, Jean-Francois Trani, Ganesh M Babulal

Abstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ramkrishna K SinghDepartment of Neurology, Washington University School of Medicine, St Louis, MO, USA.ORCID 0000-0001-9022-2317
Semere BekenaDepartment of Neurology, Washington University School of Medicine, St Louis, MO, USA.ORCID 0009-0008-6514-0502
Nikitha DameraDepartment of Neurology, Washington University School of Medicine, St Louis, MO, USA.ORCID 0009-0007-6106-1893
Yiqi ZhuDepartment of Neurology, Washington University School of Medicine, St Louis, MO, USA.ORCID 0000-0003-3400-589X
Jean-Francois TraniSchool of Public Health, Washington University in St Louis, St Louis, MO, USA.ORCID 0000-0002-9187-0946
Ganesh M BabulalDepartment of Neurology, Washington University School of Medicine, St Louis, MO, USA.ORCID 0000-0001-7966-3509

Funding

Naturalistic driving as a functional neurobehavioral marker of preclinical and symptomatic Alzheimer diseaseR01AG068183 · NIA · WASHINGTON UNIVERSITY · PI BABULAL, GANESH M · 2020 to 2024
$6.7M
The Impact of Depression and Preclinical Alzheimer Disease on Driving Among Older AdultsR01AG067428 · NIA · WASHINGTON UNIVERSITY · PI BABULAL, GANESH M · 2020 to 2024
$4.0M
Aging Research Characterizing Health Exposome via Social drivers (ARCHES)R01AG074302 · NIA · WASHINGTON UNIVERSITY · PI BABULAL, GANESH M · 2021 to 2025
$3.7M
NIA NIH HHS R01 AG067428NIA NIH HHS R01 AG068183NIA NIH HHS R01 AG074302
6 · The paper itself

Abstract

BackgroundIdentifying predictive biomarkers of cognitive decline is critical for timely intervention in early Alzheimer's disease and related dementia. Biomarkers such as cerebrospinal fluid (CSF) neurofilament light (NfL), and MRI-based hippocampal atrophy are potential indicators of neurodegeneration, but their long-term predictive value remains unclear.ObjectiveThis study examined 20-year longitudinal associations between CSF NfL, MRI-based hippocampal atrophy, and cognitive decline in cognitively normal older adults.MethodsA cohort of 279 cognitively normal adults aged ≥55 years was followed from 2003 to 2023 at the Knight ADRC. Participants underwent annual cognitive and neurological assessments, including Clinical Dementia Rating (CDR), CSF NfL quantification, and MRI-based hippocampal volumetry. Cognitive decline was defined as: (1) first progression (CDR ≥ 0.5) and (2) sustained progression (two consecutive CDRs ≥ 0.5). Analyses included Kaplan-Meier survival, Cox proportional hazards models, and linear mixed-effects (LME) models.ResultsParticipants had a mean age of 66.5 years (SD = 6.08); 58.4% were female. Mean follow-up was 11.41 years (SD = 3.5). First progression occurred in 71 participants (25.4%), and sustained progression in 35 (13%). Higher CSF NfL levels were associated with faster time to first (95% CI:0.2-1; p < 0.001) and sustained progression (95% CI:0.46-1; p = 0.008). Cox models showed increased risk of first progression (HR = 1.83; 95% CI: 1.11-3.01; p = 0.018) but not sustained (p = 0.093). LME models showed CSF NfL increase and hippocampal volume decline (p < 0.001) in both outcomes.ConclusionsCSF NfL is a strong predictor of cognitive decline and may serve as a screening biomarker for early dementia risk.

Indexed as

Cognitive DysfunctionHippocampusNeurofilament ProteinsAgedAtrophyBiomarkersCohort StudiesDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedBiomarkersneurofilament protein LNeurofilament ProteinsAlzheimer's diseasecerebrospinal fluidClinical Dementia Ratinghippocampal atrophymild cognitive impairmentMRI volumetryneurodegenerationneurofilament light chainnon-amyloid biomarkersPreclinical Alzheimer Cognitive Composite

Identifiers

PMID40785309
PMCPMC12875381

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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.