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@ARTICLE{Fleck:277508,
author = {Fleck, Lara and Buss, Claudia and Bauer, Martin and Stein,
Maike and Mekle, Ralf and Kock, Lena and Klawitter, Heiko
and Godara, Malvika and Ramler, Judith and Entringer, Sonja
and Endres, Matthias and Heim, Christine},
title = {{E}arly-{L}ife {A}dversity {P}redicts {M}arkers of
{A}ging-{R}elated {N}euroinflammation, {N}eurodegeneration,
and {C}ognitive {I}mpairment in {W}omen.},
journal = {Annals of neurology},
volume = {97},
number = {4},
issn = {0364-5134},
address = {Hoboken, NJ},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2025-00419},
pages = {642 - 656},
year = {2025},
abstract = {Despite 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.We 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.Analyses 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.These 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.},
keywords = {Humans / Female / Middle Aged / Cognitive Dysfunction:
blood / Cognitive Dysfunction: diagnostic imaging / Adult /
Aging: pathology / Neurodegenerative Diseases: blood /
Neurodegenerative Diseases: diagnostic imaging / Biomarkers:
blood / Adverse Childhood Experiences / Neurofilament
Proteins: blood / Neuroinflammatory Diseases: diagnostic
imaging / Neuroinflammatory Diseases: blood /
Neuroinflammatory Diseases: pathology / Glial Fibrillary
Acidic Protein: blood / Magnetic Resonance Imaging / Brain:
diagnostic imaging / Brain: pathology / Biomarkers (NLM
Chemicals) / Neurofilament Proteins (NLM Chemicals) / Glial
Fibrillary Acidic Protein (NLM Chemicals) / neurofilament
protein L (NLM Chemicals) / GFAP protein, human (NLM
Chemicals)},
cin = {AG Endres},
ddc = {610},
cid = {I:(DE-2719)1811005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39786167},
pmc = {pmc:PMC11889533},
doi = {10.1002/ana.27161},
url = {https://pub.dzne.de/record/277508},
}