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Published on: August 13, 2019
Female Sex and Alzheimer's Risk: The Menopause Connection
O Scheyer1, A Rahman, H Hristov
1Lisa Mosconi, PhD, Department of Neurology, Weill Cornell Medicine, 428 East 72nd St, Suite 500, Room 407, New York, NY, 10021; Tel: (212) 746-4624,
The Journal of Prevention of Alzheimer'S Disease
|October 10, 2018
Summary
Female sex is a major risk factor for Alzheimer's disease (AD). The menopause transition (MT) uniquely impacts women's brain energy, increasing AD risk.
Area of Science:
- Neuroscience
- Endocrinology
- Gerontology
Background:
- Female sex, advanced age, and APOE-4 genotype are key Alzheimer's disease (AD) risk factors.
- Women's higher AD risk isn't solely due to longer lifespan; sex-specific mechanisms are involved.
- The menopause transition (MT), a midlife neuroendocrine shift, is implicated in female AD risk.
Purpose of the Study:
- To review the role of the menopause transition (MT) in Alzheimer's disease (AD) risk for women.
- To explore the neurobiological changes during MT that may predispose women to AD.
- To identify the MT as a critical window for AD prevention strategies.
Main Methods:
- Review of preclinical and translational brain imaging studies.
- Analysis of estrogen's role in brain bioenergetics during MT.
- Comparison of metabolic activity and amyloid-beta deposition in women across the MT spectrum and men.
Main Results:
- During MT, estrogen networks decouple from brain energy systems, causing hypometabolism.
- Perimenopausal and postmenopausal women show AD-endophenotypes (reduced brain metabolism, increased amyloid-beta).
- These changes are evident in 40-60 year-old women compared to premenopausal women and age-matched men.
Conclusions:
- The MT represents a critical period of brain bioenergetic vulnerability in women.
- Therapeutic interventions targeting MT could mitigate AD risk.
- Addressing the brain energy crisis during MT is key to combating AD in women.
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