The global increase in aging populations has heightened the urgency to develop effective interventions for age-related cognitive decline. Skeletal muscle has recently emerged as a potential modulator of brain health, particularly in the context of aging. This study investigates the effects of electrical muscle stimulation (EMS) on cognitive function and neuropathology in Senescence-Accelerated Mouse (SAMP8), a model of aging-associated cognitive decline. SAMP8 mice were divided into 3 groups: healthy controls (SAMR1), untreated SAMP8, and EMS-treated SAMP8. EMS was applied daily for 30 days, and behavioral, histological, and molecular markers were analyzed. Results demonstrated that EMS significantly improved muscle strength and endurance while reducing amyloid-β accumulation and phosphorylated tau (p-Tau) levels in the hippocampus. Furthermore, EMS decreased neuroinflammation and partially restored synaptic plasticity. However, EMS had limited effects on cortical pathology and cognitive function, suggesting that localized brain changes may not fully translate to behavioral improvements. These findings indicate that EMS exerts neuroprotective effects through skeletal muscle activation, providing a potential non-pharmacological intervention for age-related neurodegeneration. Future studies should explore the underlying mechanisms and translational applicability to human dementia treatment.
