Impact of Reproductive Aging on Memory Circuitry

Cognitive neuroscience of aging studies traditionally target participants age 65 and older. However, converging preclinical and human evidence indicates that the decline in ovarian estradiol production during the menopausal transition may play a mechanistic role in neuronal changes that occur earlier in the aging process. In a series of studies, we step back by over a decade to characterize the changes in memory circuitry that occur in early midlife (age ~45-55), as a function of sex, women’s reproductive stage and sex steroid hormone concentrations. 

Given accumulating evidence of estradiol’s key role in memory circuitry, the loss of ovarian estrogens during the menopausal transition may play a significant role in shaping early age-related neural changes in women. In collaboration with Dr. Jill Goldstein (Harvard Medical School), we are investigating this in a large-scale, population-based fMRI study of mid-life men and women. Findings demonstrate that the natural depletion of sex steroid hormones in midlife alters neural mechanisms of working memory. These findings underscore the importance of considering the role of reproductive age, independent of chronologic age, to strengthen our understanding of early neuronal changes that occur in the middle decades of life.

  • Broadly, these data suggest that a complete understanding of PFC function – be it in the young healthy brain or in the aging brain – must include a role for sex steroids. 
  • In future studies we will be exploring the relationship between the midlife ovarian decline in neuroactive gonadal hormones, dopaminergic signaling, and working memory. 
  • Taking into account gene-hormone interactions could reveal individual differences regarding the impact of reproductive aging on working memory.