Inflammatory cytokine levels implicated in Alzheimer's disease moderate the effects of sex on verbal memory performance

Brain Behav Immun. 2021 Jul:95:27-35. doi: 10.1016/j.bbi.2020.12.001. Epub 2020 Dec 8.


Despite having an initial verbal memory advantage over men, women have greater rates of Alzheimer's disease and more rapid cognitive decline once diagnosed. Moreover, although Alzheimer's disease is influenced by inflammation, which itself has known sex differences, no study has investigated whether sex differences in memory are moderated by peripheral inflammatory activity. To address this issue, we analyzed data from 109 individuals (50 women, Mage = 71.62, range = 55-87) diagnosed as cognitively normal, or having mild cognitive impairment or Alzheimer's disease dementia. We then followed the sample for 12 months, as part of a longitudinal study of aging and Alzheimer's disease. At baseline, we assessed levels of the inflammatory cytokines interleukin (IL)-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in plasma. At baseline and 12 months, we assessed verbal memory using the Rey Auditory Verbal Learning Test and nonverbal memory using the Brief Visuospatial Memory Test-Revised. As hypothesized, for the full sample, women exhibited stronger verbal (but not nonverbal) memory than men. In women, but not men, higher IL-1β at baseline related to poorer verbal learning across both time points and delayed recall at 12 months. The effect of sex on memory also differed by IL-1β level, with women exhibiting a memory advantage both at baseline and 12 months, but only for those with low-to-moderate IL-1β levels. Therefore, high peripheral inflammation levels may lead to a sex-specific memory vulnerability relevant for Alzheimer's disease.

Keywords: Alzheimer’s disease; Cognition; Inflammation; Mechanisms; Memory; Pathophysiology; Risk; Sex differences; Symptoms; Vulnerability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease*
  • Cytokines
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Memory
  • Neuropsychological Tests


  • Cytokines