Impact of sex and reproductive status on the default mode network in early midlife: implications for aging of memory circuitry and function

Abstract

Alterations to the resting-state default mode network (rsDMN) are early indicators of memory decline and Alzheimer's disease (AD). Brain regions shared by the rsDMN and memory circuitry are highly sexually dimorphic. However, data are limited regarding the impact of sex and reproductive status on rsDMN connectivity and memory circuitry and function. In the current investigation, rsDMN connectivity was assessed in 180 early midlife adults aged 45 to 55 by sex and reproductive status (87 women; 93 men). Associations between left and right hippocampal connectivity of rsDMN and verbal memory encoding circuitry were examined using linear mixed models, controlled for age and parental socioeconomic status, testing interactions by sex and reproductive status. Relative to men, women exhibited greater rsDMN connectivity between the left and right hippocampus. In relation to rsDMN-memory encoding connectivity, sex differences were revealed across the menopausal transition, such that only postmenopausal women exhibited loss of the ability to decrease rsDMN left-right hippocampal connectivity during memory encoding associated with poorer memory performance. Results demonstrate that sex and reproductive status play an important role in aging of the rsDMN and interactions with memory circuitry/function. This suggests the critical importance of sex and reproductive status when studying early midlife indicators of memory decline and AD risk.

Keywords: DMN; estradiol; hippocampus; menopause; resting state.