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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},
}