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000277508 1001_ $$00000-0001-9436-5008$$aFleck, Lara$$b0
000277508 245__ $$aEarly-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.
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000277508 520__ $$aDespite the overwhelming evidence for profound and longstanding effects of early-life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood-based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle-aged women.We recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty. Using Simoa technology, we assessed blood-based markers of neuroinflammation and neurodegeneration, including serum concentrations of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). We further obtained T1-weighted and T2-weighted magnetic resonance images to assess brain volumes and we assessed cognitive performance sensitive to early impairments associated with the development of dementia, using the Cambridge Neuropsychological Automated Test Battery. We used generalized additive models to examine nonlinear interaction effects of ELS severity and age on these outcomes.Analyses revealed significant nonlinear interaction effects of ELS severity and age on NfL and GFAP serum concentrations, total and subcortical gray matter volume loss, increased third ventricular volume, and cognitive impairment.These findings suggest that ELS profoundly exacerbates peripheral, neurostructural, and cognitive markers of brain aging. Our results are critical for the development of novel early prevention strategies that target the impact of developmental stress on the brain to mitigate aging-related neurological diseases. ANN NEUROL 2025;97:642-656.
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000277508 650_7 $$2NLM Chemicals$$aBiomarkers
000277508 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000277508 650_7 $$2NLM Chemicals$$aGlial Fibrillary Acidic Protein
000277508 650_7 $$2NLM Chemicals$$aneurofilament protein L
000277508 650_7 $$2NLM Chemicals$$aGFAP protein, human
000277508 650_2 $$2MeSH$$aHumans
000277508 650_2 $$2MeSH$$aFemale
000277508 650_2 $$2MeSH$$aMiddle Aged
000277508 650_2 $$2MeSH$$aCognitive Dysfunction: blood
000277508 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000277508 650_2 $$2MeSH$$aAdult
000277508 650_2 $$2MeSH$$aAging: pathology
000277508 650_2 $$2MeSH$$aNeurodegenerative Diseases: blood
000277508 650_2 $$2MeSH$$aNeurodegenerative Diseases: diagnostic imaging
000277508 650_2 $$2MeSH$$aBiomarkers: blood
000277508 650_2 $$2MeSH$$aAdverse Childhood Experiences
000277508 650_2 $$2MeSH$$aNeurofilament Proteins: blood
000277508 650_2 $$2MeSH$$aNeuroinflammatory Diseases: diagnostic imaging
000277508 650_2 $$2MeSH$$aNeuroinflammatory Diseases: blood
000277508 650_2 $$2MeSH$$aNeuroinflammatory Diseases: pathology
000277508 650_2 $$2MeSH$$aGlial Fibrillary Acidic Protein: blood
000277508 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000277508 650_2 $$2MeSH$$aBrain: diagnostic imaging
000277508 650_2 $$2MeSH$$aBrain: pathology
000277508 7001_ $$aBuss, Claudia$$b1
000277508 7001_ $$aBauer, Martin$$b2
000277508 7001_ $$aStein, Maike$$b3
000277508 7001_ $$aMekle, Ralf$$b4
000277508 7001_ $$aKock, Lena$$b5
000277508 7001_ $$aKlawitter, Heiko$$b6
000277508 7001_ $$aGodara, Malvika$$b7
000277508 7001_ $$aRamler, Judith$$b8
000277508 7001_ $$aEntringer, Sonja$$b9
000277508 7001_ $$0P:(DE-2719)2811033$$aEndres, Matthias$$b10
000277508 7001_ $$00000-0002-6580-6326$$aHeim, Christine$$b11
000277508 773__ $$0PERI:(DE-600)2037912-2$$a10.1002/ana.27161$$gVol. 97, no. 4, p. 642 - 656$$n4$$p642 - 656$$tAnnals of neurology$$v97$$x0364-5134$$y2025
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