Adverse childhood experiences interact with inflammation and menopause transition stage to predict verbal memory in women

Christina A Metcalf; Rachel L Johnson; Andrew M Novick; Ellen W Freeman; Mary D Sammel; Laura G Anthony; C Neill Epperson

doi:10.1016/j.bbih.2022.100411

Adverse childhood experiences interact with inflammation and menopause transition stage to predict verbal memory in women

Brain Behav Immun Health. 2022 Jan 5:20:100411. doi: 10.1016/j.bbih.2022.100411. eCollection 2022 Mar.

Authors

Christina A Metcalf¹, Rachel L Johnson², Andrew M Novick¹, Ellen W Freeman³, Mary D Sammel^{1

2}, Laura G Anthony¹, C Neill Epperson^{1

4}

Affiliations

¹ Department of Psychiatry, University of Colorado-Anschutz Medical Campus, Aurora, CO, 80045, USA.
² Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, Aurora, CO, 80045, USA.
³ Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁴ Department of Family Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, 80045, USA.

Abstract

Objective: Women with more adverse childhood experiences (ACEs) may face a triple threat of risk factors for cognitive concerns during the menopause transition: reduced estradiol, increased inflammation, and early life stress sequelae. Our objective was to determine the extent to which ACEs and peripheral basal inflammatory markers associate with verbal memory across the menopause transition.

Methods: Penn Ovarian Aging cohort participants (n = 167) were assessed for ACEs (low (0-1) or high (≥2)) and had remaining stored blood samples at study end assayed for interleukin (IL)-6, IL-1-beta (IL-1β), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α). Annual assessment included a verbal memory test (the Buschke Selective Reminding Test) and menopause stage determination. To estimate the effects of menopause stage, ACEs, and cytokines on verbal memory, repeated cognitive outcome measures were modeled in generalized estimating equations. Covariates included body mass index, smoking, race, education, age at baseline, and baseline verbal memory performance. Cytokine levels were log-transformed.

Results: Advancing menopause stage was associated with worse performance on immediate verbal recall and delayed verbal recall (ps < 0.001). During perimenopause, higher ACE exposure was associated with worse immediate verbal recall at higher levels of TNF-α (slope difference p = 0.041).

Conclusions: Inflammation may mechanistically link ACEs and verbal memory for high ACE women during perimenopause. Reducing inflammation for these individuals may have positive impact on verbal memory across the menopause transition.

Keywords: Childhood adversity; Cognition; Inflammation; Menopausal status; Menopause.

Grants and funding

L30 HD106379/HD/NICHD NIH HHS/United States