Many women report increased forgetfulness earlier in the aging process, as they transition to menopause, epidemiological surveys show.
Maintaining intact memory function with age is one of the greatest public health challenges of our time, and women have an increased risk for memory disorders relative to men later in life.
‘Lower 17β-estradiol concentrations are related to more pronounced alterations in hippocampal connectivity and poorer performance on a subsequent memory retrieval task.’
In the study published in the Journal Of Neuroscience
, researchers conducted functional Magnetic Resonance Imaging (fMRI) study on 200 women aged 45-55 years to characterize the changes in memory circuitry that occur in early midlife, as a function of sex and women's reproductive stage.
Participants performed a verbal encoding task during fMRI scanning.
Reproductive histories and serology evaluations were used to determine menopausal status.
Results revealed a pronounced impact of reproductive stage on task-evoked hippocampal responses, despite minimal difference in chronological age.
Researchers then examined the impact of sex and reproductive stage on functional connectivity across brain regions associated with tasks.
Postmenopausal women showed enhanced bilateral hippocampal connectivity relative to premenopausal and perimenopausal women.
Across women, lower 17β-estradiol concentrations were related to more pronounced alterations in hippocampal connectivity and poorer performance on a subsequent memory retrieval task, strongly implicating sex steroids in the regulation of this circuitry.
Finally, subgroup analyses revealed that high-performing postmenopausal women (relative to low and middle performers) exhibited a pattern of brain activity akin to premenopausal women.
Together, these findings underscore the importance of considering reproductive stage, not simply chronological age, to identify neuronal and cognitive changes that unfold in the middle decades of life. In keeping with preclinical studies, these human findings suggest that the decline in ovarian estradiol production during menopause plays a significant role in shaping memory circuitry.
Results demonstrate regional and network-level differences in memory encoding-related activity as a function of women's reproductive stage, independent of chronological age.
These findings suggest that early changes in memory circuitry are evident decades before the age range traditionally targeted by cognitive neuroscience of aging studies.