Women's Pregnancy Life History and Alzheimer's Risk: Can Immunoregulation Explain the Link?

Molly Fox, C Berzuini, Leslie A Knapp, Laura M Glynn

Research output: Contribution to journalArticlepeer-review


Background: Pregnancy is associated with improvement in immunoregulation that persists into the geriatric phase. Impaired immunoregulation is implicated in Alzheimer’s disease (AD) pathogenesis. Hence, we investigate the relationship between pregnancy and AD. Methods: Cross-sectional cohort of British women (N = 95). Cox proportional hazards modeling assessed the putative effects of cumulative months pregnant on AD risk and the mutually adjusted effects of counts of first and third trimesters on AD risk. Results: Cumulative number of months pregnant, was associated with lower AD risk (β = −1.90, exp(β) = 0.15, P = .02). Cumulative number of first trimesters was associated with lower AD risk after adjusting for third trimesters (β = −3.83, exp(β) = 0.02, P < .01), while the latter predictor had no significant effect after adjusting for the former. Conclusions: Our observation that first trimesters (but not third trimesters) conferred protection against AD is more consistent with immunologic effects, which are driven by early gestation, than estrogenic exposures, which are greatest in late gestation. Results may justify future studies with immune biomarkers.
Original languageEnglish
Pages (from-to)516-526
Number of pages11
JournalAmerican Journal of Alzheimer's Disease and other Dementias
Issue number8
Early online date30 Jul 2018
Publication statusPublished - Jul 2018


  • adaptive immunity
  • Alzheimer’s disease
  • autoimmunity
  • immunoregulation
  • parity
  • pregnancy
  • reproductive history


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