Evidence map›Paper›PMID 39786167›Full record

ArticleAnnals of neurology2025

Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.

Lara Fleck, Claudia Buss, Martin Bauer, Maike Stein, Ralf Mekle, Lena Kock, Heiko Klawitter, Malvika Godara, Judith Ramler, Sonja Entringer and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Targeting enhancing myelin regeneration reverses cognitive deficits in a mouse model of intellectual disability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  4. Review
  5. Review
  6. Advancing brain health equity with Indigenous peoples: A critical imperative.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  7. Article
  8. Review
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

12 authors.

Lara FleckCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.ORCID 0000-0001-9436-5008
Claudia BussCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Martin BauerCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Maike SteinDepartment of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Ralf MekleCenter for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Lena KockCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Heiko KlawitterCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Malvika GodaraCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Judith RamlerCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Sonja EntringerCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Matthias EndresGerman Center for Mental Health, Berlin, Germany.ORCID 0000-0001-6520-3720
Christine HeimCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.ORCID 0000-0002-6580-6326

Funding

Deutsche Forschungsgemeinschaft EXC257
6 · The paper itself

Abstract

objectiveDespite the overwhelming evidence for profound and longstanding effects of early-life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood-based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle-aged women.

methodsWe recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty. Using Simoa technology, we assessed blood-based markers of neuroinflammation and neurodegeneration, including serum concentrations of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). We further obtained T1-weighted and T2-weighted magnetic resonance images to assess brain volumes and we assessed cognitive performance sensitive to early impairments associated with the development of dementia, using the Cambridge Neuropsychological Automated Test Battery. We used generalized additive models to examine nonlinear interaction effects of ELS severity and age on these outcomes.

resultsAnalyses revealed significant nonlinear interaction effects of ELS severity and age on NfL and GFAP serum concentrations, total and subcortical gray matter volume loss, increased third ventricular volume, and cognitive impairment.

interpretationThese findings suggest that ELS profoundly exacerbates peripheral, neurostructural, and cognitive markers of brain aging. Our results are critical for the development of novel early prevention strategies that target the impact of developmental stress on the brain to mitigate aging-related neurological diseases. ANN NEUROL 2025;97:642-656.

Indexed as

Adverse Childhood ExperiencesAgingCognitive DysfunctionNeurodegenerative DiseasesNeuroinflammatory DiseasesAdultBiomarkersBrainFemaleGlial Fibrillary Acidic ProteinHumansMagnetic Resonance ImagingMiddle AgedNeurofilament ProteinsBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament Proteins

Identifiers

PMID39786167
PMCPMC11889533

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.