Estrogen, Cognitive Performance, and Functional Imaging Studies: What Are We Missing About Neuroprotection?

Area of Science:

• Neuroendocrinology and Cognitive Aging
• Reproductive Health and Systemic Inflammation

Background:

• Menopause transition is linked to estrogen deficiency, contributing to chronic inflammation and age-related disorders, including cognitive impairment.
• Estrogen exerts beneficial neurological, cardioprotective, and anti-inflammatory effects throughout life, but clinical hormone treatment efficacy in menopausal women remains debated.
• Enhanced verbal memory is a consistent finding in studies of aging and estrogen, yet estrogen's impact on brain activity and functional connectivity is under-explored.

Purpose of the Study:

• To explore the potential of resting-state functional connectivity and brain imaging to understand reproductive aging and hormonal treatment effects on cognition.
• To review cognitive tasks in animal models for evaluating hormone treatment effects on cognitive performance, identifying those suitable for human studies.
• To examine studies on the default mode network (DMN) activity and its response to pharmacological stimulation in humans concerning estrogen's role.

Main Methods:

• Review of longitudinal and cross-sectional studies on cognitive function during menopause.
• Analysis of resting-state functional connectivity paradigms in relation to aging and hormone therapy.
• Comprehensive review of cognitive tasks used in animal research and their applicability to human clinical trials.
• Focus on studies investigating default mode network (DMN) activity and pharmacological modulation.

Main Results:

• Enhanced verbal memory is the most robust cognitive finding associated with estrogen.
• The role of estrogen in brain activity and functional connectivity during menopause requires further investigation using advanced neuroimaging techniques.
• The resting-state paradigm offers a promising approach to study aging-related brain changes and hormonal treatment impacts.

Conclusions:

• Understanding estrogen's neuroprotective effects, particularly on verbal memory, necessitates further research into brain activity and functional connectivity.
• The resting-state functional connectivity paradigm, combined with brain imaging, is crucial for elucidating the cognitive protective effects of estrogen.
• Future research should focus on translating findings from animal cognitive tasks to human studies and investigating DMN activity in response to hormonal changes and treatments.