Women comprise nearly two-thirds of Alzheimer's diagnoses, and the menopausal transition emerges as a discrete neurological vulnerability window — not merely an endocrine event. Estrogen withdrawal disrupts synaptic plasticity, cerebral glucose metabolism, mitochondrial efficiency, and neuroinflammatory signaling simultaneously. Exercise interventions in postmenopausal women demonstrate measurable improvements across executive function, memory, and global cognition, with neuroimaging confirming exercise-associated gains in hippocampal volume, cortical thickness, functional connectivity, and cerebral blood flow. Aerobic training primarily benefits cerebrovascular integrity and hippocampal preservation; resistance training targets executive function and white matter; multimodal protocols combining both with balance and cognitive challenge produce the broadest gains. BDNF upregulation, improved insulin sensitivity, and reduced systemic inflammation represent the core converging mechanisms.
This review synthesizes a genuinely important but underappreciated clinical picture: menopause is not a neutral aging event but a hormonally-driven inflection point that may compress the timeline toward neurodegeneration in women. The "timing hypothesis" — that earlier exercise initiation post-menopause confers greater neuroprotection — is mechanistically plausible given estrogen's role in maintaining neural infrastructure before structural deficits accumulate. However, as a narrative review rather than meta-analysis or RCT, it cannot quantify effect sizes or establish causality. The modality-specific findings, while biologically coherent, derive largely from studies not designed for head-to-head comparisons. For practicing clinicians and health-conscious women in their late 40s and 50s, the actionable takeaway is clear: multimodal exercise started at perimenopause, not retirement, is the most defensible non-pharmacological brain-protective strategy currently available.
