Memory and Brain Aging
Women have almost double the frequency of memory disorders compared to men. While this may be partially attributable to life expectancy, there are sex-dependent brain & physiologic factors that contribute to the higher frequency of Alzheimer’s disease (AD) in women.
Most work on cognitive aging is conducted in study samples over the age 60 years, but we now know that vulnerability is expressed in early midlife (late 40’s and 50’s), a period during which women transition into menopause.
Our team has taken a developmental approach to thinking about sex differences in brain aging. We are mapping out sex-dependent developmental pathways that result in sex differences in memory decline in early midlife. We believe these sex-dependent developmental pathways, which include hormone, genetic, metabolic (e.g., insulin, glucose), and immune pathways, lay the foundation for why we see sex differences in AD. We have been following a prenatal cohort for over 50 years to investigate these developmental pathways on sex differences in memory circuitry aging. Dr. Kyoko Konishi is leading our team in studies of sex differences in hormonal and genetic regulation of memory circuitry aging. We argue that understanding the sex-dependent risk for AD will be critical in the development of sex-dependent therapeutics and prevention strategies for AD.
HATCH: Healthy Aging Translational Cohort
We have also initiated the Healthy Aging Translational Cohort (HATCH), composed of individuals between the ages of 45-70 (with a goal of n=5,000), that will be used to develop a sex-dependent clinical risk algorithm that identifies, in early midlife, who is at highest risk for AD later in life. The clinical risk algorithm will identify target populations for early therapeutic intervention and will allow us to establish a resource for future generations to follow into old age.
The Healthy Aging Translational Cohort (HATCH) is currently seeking a Clinical Research Coordinator to work on studies within the Clinical Neuroscience Laboratory of Sex Differences in the Brain. For more details on the position, click here.
Examples of findings:
In early midlife, women outperform men on verbal and associative memory tasks. However, this female advantage is attenuated postmenopause due to estradiol decline, underscoring the impact of ovarian decline in shaping memory function in women (Rentz et al. 2016).
Reproductive age has a pronounced regional and network level impact on task-evoked hippocampal response, independent of chronological age. During episodic memory encoding, task-evoked hippocampal responses decrease over the menopausal transition and correlate with decreasing levels of 17β-estradiol. In compensation, postmenopausal women show enhanced bilateral hippocampal connectivity (Jacobs et al. 2016a).
Reproductive aging is associated with reorganization of the functional networks in the working memory circuitry. Over the menopausal transition, there is a shift in reliance from connectivity between the dorsolateral prefrontal cortex and inferior parietal cortex to the dorsolateral prefrontal cortex and hippocampal pathways to maintain working memory performance. These findings suggest that changes in working memory circuitry are evident in early midlife, decades before the onset of cognitive impairment (Jacobs et al. 2016b).