Female Sex and Alzheimer's Risk: The Menopause Connection.

TitleFemale Sex and Alzheimer's Risk: The Menopause Connection.
Publication TypeJournal Article
Year of Publication2018
AuthorsScheyer O, Rahman A, Hristov H, Berkowitz C, Isaacson RS, R Brinton D, Mosconi L
JournalJ Prev Alzheimers Dis
Date Published2018
KeywordsAlzheimer Disease, Brain, Female, Hormone Replacement Therapy, Humans, Menopause, Risk Factors

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.

Alternate JournalJ Prev Alzheimers Dis
PubMed ID30298180
PubMed Central IDPMC6198681
Grant ListP01 AG026572 / AG / NIA NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States

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