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Dopamine-dependent cognitive processes after menopause: the relationship between COMT genotype, estradiol, and
Julie A Dumas1, Jenna A Makarewicz1, Janice Bunn2
1Department of Psychiatry, University of Vermont Robert Larner, M.D. College of Medicine, Burlington, VT.
Neurobiology of Aging
|September 14, 2018
Summary
Catechol-O-methyltransferase (COMT) genotype and estradiol levels did not significantly impact working memory brain activation in postmenopausal women. A COMT-estradiol interaction affected frontal lobe activation, but cognitive performance remained unchanged.
Area of Science:
- Neuroscience
- Genetics
- Endocrinology
Background:
- The dopaminergic system is crucial for cognitive functions like working memory.
- Catechol-O-methyltransferase (COMT) influences dopamine levels, and estradiol is a key hormone affected by menopause.
- Understanding their interplay is vital for cognitive health in aging women.
Purpose of the Study:
- To investigate the relationship between COMT genotype, estradiol levels, and brain functioning during a working memory task in healthy postmenopausal women.
- To explore how these factors interact to influence neural activation patterns.
Main Methods:
- 118 healthy postmenopausal women (50-60 years) underwent BOLD fMRI during an N-back task.
- Blood samples analyzed for COMT genotype and estradiol levels.
- Participants categorized into high/low estradiol groups based on median split for each genotype.
Main Results:
- The N-back task activated expected working memory networks (frontal, parietal).
- No main effects of COMT genotype or estradiol levels on brain activation or task performance were observed.
- A significant COMT-estradiol interaction revealed altered activation in the right precentral gyrus (Brodmann Area 6) related to hypothesized dopamine levels.
Conclusions:
- Postmenopausal COMT genotype and estradiol levels do not appear to directly influence overall cognition or working memory brain activation.
- The observed interaction suggests a complex interplay affecting specific frontal regions.
- Further research is needed to explore these relationships around the menopause transition, as findings may differ from premenopausal women.
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