"THE SILENT BURDEN: UNRAVELING WOMEN’S HIGHER RISK OF ALZHEIMER’S AND PATHS TO PREVENTION"

Amit Mia*, Partha Pratim Mahata, Milan Kumar Maity, Ms. Sneha Shaw

ABSTRACT

Dementia is most commonly caused by Alzheimer's disease, a degenerative brain illness. Dementia's typical symptoms include challenges with language, remembering, and solving problems additional cognitive abilities that impact an individual's capacity to execute regular activities. Female sex, together with advanced age and the apolipoprotein E (APOE)-4 genotype, is a significant risk factor for late-onset Alzheimer's disease. Given that AD pathology begins decades before clinical symptoms appear, women's increased risk cannot be attributed solely to their longer life expectancy. Recent research into the sex-specific pathophysiological mechanisms behind AD risk has identified the menopause transition (MT). Many symptoms of MT, which typically ends in reproductive senescence, are neurological in nature, including disturbance of estrogen-regulated systems such as thermoregulation, sleep, and circadian rhythms, depression and impairment in multiple cognitive domains. Preclinical investigations have indicated that during MT, the estrogen network separates from the brain bioenergetic system. The ensuing hypometabolic state may act as a basis for neurological impairment. Indeed, translational brain imaging studies show that 40-60-year-old perimenopausal and postmenopausal women have an AD-endophenotype defined by lower metabolic activity and higher brain amyloid-beta deposition as compared to premenopausal women and age-matched males. This review highlights the MT as a window of opportunity for therapeutic approaches to correct for brain bioenergetic crisis and reduce the consequent elevated risk of Alzheimer's disease in women. Drugs have entered the clinical trials, like AN-1792, solanezumab, bapineuzumab, semagacestat, avagacestat and tarenflurbil for the treatment of Alzheimer`s disease. More research is needed to find cure for Alzheimer's disease.

Keywords: Dementia, Alzheimer’s disease, Apolipoprotein, Hypometabolic, Pregnancy complication.