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

Authors: Lara Fleck,Claudia Buss,Martin Bauer,Maike Stein,Ralf Mekle,Lena Kock,Heiko Klawitter,Malvika Godara,Judith Ramler,Sonja Entringer,Matthias Endres,Christine Heim
Journal: Annals of Neurology
Publisher: Wiley
Publish date: 2025-1-9
ISSN: 0364-5134 DOI: 10.1002/ana.27161
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Your core rationale for studying only women was to test a hypothesis of heightened vulnerability in women compared to men. But you didn’t include a male comparison group.
That’s not a high-risk design; it’s a sex‑limited sample that cannot support any claim about sex‑specific vulnerability or disproportionate risk.

So my main technical question is:

How do you justify interpreting your findings as evidence of vulnerability of women for ELS‑related AD mechanisms when your study has no male group to assess whether the effects differ by sex?

Without that, the framing in the interpretation section is scientifically unsupported; it’s not a design limitation you can wave away; it’s a logical disconnect between the stated aim and the actual evidence you produced.

A second, related issue: you defined ELS exposure by ACEs before menarche, but then used menarche as a developmental cutoff without checking whether the age of menarche itself is a downstream effect of ELS. If ELS affects pubertal timing, your exposure classification becomes partially collider‑biased. Did you test for that; and if so, how did you rule out bias rather than just reporting no correlation?

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