A multi-sensory digital treatment protocol, incorporating sensory integration, sensory substitution, and sensory masking (e.g., blindfolding), significantly improved participants’ performance on spatial memory tasks. Resting-state fMRI analysis showed that these improvements were associated with enhanced connectivity between memory-related brain regions, executive frontal areas, and the default mode network (DMN). This protocol holds promise for mitigating the effects of age-related cognitive decline, potentially supporting healthier aging and longevity by improving brain connectivity in both healthy individuals and patients with mild cognitive impairments (MCI) or Alzheimer’s Disease (AD).