Female Sex and Alzheimer’s Risk: The Menopause Connection

Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer’s disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater long...

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Bibliographic Details
Published in:The journal of prevention of Alzheimer's disease 2018, Vol.5 (4), p.225-230
Main Authors: Scheyer, O., Rahman, A., Hristov, H., Berkowitz, C., Isaacson, R. S., Diaz Brinton, R., Mosconi, Lisa
Format: Article
Language:English
Subjects:
Alzheimer Disease - etiology
Alzheimer Disease - physiopathology
Alzheimer Disease - prevention & control
Brain - physiopathology
Female
Geriatrics/Gerontology
Hormone Replacement Therapy
Humans
Medicine
Medicine & Public Health
Menopause
Neurology
Original Research
Risk Factors
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Summary:Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer’s disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Commonly characterized as ending in reproductive senescence, many symptoms of MT are neurological, including disruption of estrogen-regulated systems such as thermoregulation, sleep, and circadian rhythms, as well as depression and impairment in multiple cognitive domains. Preclinical studies have shown that, during MT, the estrogen network uncouples from the brain bioenergetic system. The resulting hypometabolic state could serve as the substrate for neurological dysfunction. Indeed, translational brain imaging studies demonstrate that 40–60 year-old perimenopausal and postmenopausal women exhibit an AD-endophenotype characterized by decreased metabolic activity and increased brain amyloid-beta deposition as compared to premenopausal women and to age-matched men. This review discusses the MT as a window of opportunity for therapeutic interventions to compensate for brain bioenergetic crisis and combat the subsequent increased risk for AD in women.
ISSN:2274-5807
2426-0266
DOI:10.14283/jpad.2018.34