Objective: 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.
Methods: 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.
Results: 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.
Interpretation: 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ana.27161 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
DNA damage and its links to neuronal aging and degeneration.
Neuron
January 2025
Departments of Psychiatry, Neuroscience, and Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Peter O' Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:
DNA damage is a major risk factor for the decline of neuronal functions with age and in neurodegenerative diseases. While how DNA damage causes neurodegeneration is still being investigated, innovations over the past decade have provided significant insights into this issue. Breakthroughs in next-generation sequencing methods have begun to reveal the characteristics of neuronal DNA damage hotspots and the causes of DNA damage.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Turner Institute for Brain and Mental Health & School of Psychological Sciences, Monash University, Clayton, VIC, Australia.
Background: Plasma and cerebrospinal (CSF) biomarkers are promising candidates for detecting neuropathology. While CSF biomarkers directly reflect pathophysiological processes within the central nervous system, their requirement for a lumbar puncture is a barrier to their widespread scalability in practice. Therefore, we examined cross-sectional associations of plasma biomarkers of amyloid (Aβ42/Aβ40 and pTau-181), neurodegeneration (Neurofilament Light, NfL), and neuroinflammation (Glial Fibrillary Acidic Protein, GFAP) with brain volume, cognition, and their corresponding CSF levels.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Neurology Department, Hospital Universitario Marqués de Valdecilla - IDIVAL - University of Cantabria - CIBERNED, Madrid, Spain.
Background: Recent reports support the use of plasma biomarkers of neurodegeneration and neuroinflammation, as determined through ultrasensitive single molecular arrays (SIMOA), to screen and diagnose patients with dementia. However, their translation to clinical settings requires further studies.
Methods: We evaluated plasma samples from 186 individuals including 72 patients with AD (supported by CSF biomarkers consistent with an A+T+N+ classification scheme), 44 with confirmed FTD, 48 cognitively intact nonagenarians, and 22 controls (ages 40-83 years).
Background: Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain.
Method: We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n=104), Alzheimer's disease (AD, n=76) and neurological controls (NC, n=27).
Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.
Ann Neurol
January 2025
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Medical Psychology, Berlin, Germany.
Objective: 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.
Methods: We recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!