The global healthcare landscape faces a mounting challenge as 1.2 billion women approach menopause by 2050, each potentially entering a critical vulnerability window for cognitive decline. This reality demands urgent attention to how hormonal transitions fundamentally reshape brain health trajectories. New evidence reveals that women's disproportionate Alzheimer risk—comprising nearly two-thirds of cases—extends far beyond simple longevity advantages. The menopause transition triggers neuroendocrine changes that create distinct biological pathways to cognitive impairment, challenging decades of gender-neutral prevention approaches. Key risk amplifiers include early menopause onset, surgical removal of ovaries before natural menopause, severe hot flashes, and midlife mood disturbances. Each represents a measurable biological signal that current medical practice largely overlooks. The research identifies hormone therapy as a potentially powerful intervention, particularly for women undergoing oophorectomy, yet clinical implementation remains constrained by insufficient trial data and biomarker validation. This represents a paradigm shift from viewing Alzheimer disease as an inevitable consequence of aging toward recognizing midlife as a targetable prevention opportunity. The implications extend beyond individual health outcomes to global public health strategy. Current prevention frameworks treat cognitive decline as a late-life inevitability rather than a midlife-modifiable trajectory. This perspective fundamentally misaligns resources and timing, potentially missing the most impactful intervention window. As healthcare systems worldwide grapple with dementia's rising prevalence, this research suggests that women's midlife healthcare deserves elevated priority and specialized approaches rather than generalized aging interventions.