Memory Enhancement in Aging With Optimal Dosing

Cognitive decline, especially in memory and executive control, poses an escalating publichealth challenge as the population ages, contributing to loss of independence, reducedquality of life, and increased healthcare costs associated with Alzheimer's disease andrelated dementias (ADRD). Despite decades of research, there are few effective,non‐pharmacological interventions capable of slowing or reversing these cognitive losses.Transcranial alternating current stimulation (tACS) has recently emerged as a promising,safe, and non‐invasive technique for modulating neural rhythms that support memory.However, existing approaches remain limited by one‐size‐fits‐all stimulation schedulesthat fail to account for individual brain connectivity patterns or dynamic fluctuationsin cognitive state.This project aims to advance precision neuromodulation for cognitive aging by optimizingand personalizing high‐resolution tACS protocols to enhance memory in older adults.Building on strong pilot data demonstrating the feasibility of personalized and adaptivestimulation, we will use multimodal imaging (EEG and fMRI) to track changes infrontotemporal synchrony, specifically theta‐gamma phase‐amplitude coupling and thetaphase synchronization, that are known to support memory formation and retrieval.Aim 1 will establish how stimulation pattern (patterned vs. continuous waveforms) andschedule (one, three, or five consecutive days) shape the durability of memoryenhancement. By comparing six systematically varied dosing protocols, we will determinethe optimal pattern and repetition schedule that maximize and sustain improvements inworking memory capacity, interference control, and long‐term memory recognition over onemonth.By integrating behavioral, electrophysiological, and neuroimaging measures with adaptivecontrol algorithms, this research will identify reliable biomarkers of responsiveness,elucidate causal mechanisms linking neural synchrony to memory, and yield a new class ofpersonalized, connectivity‐guided interventions for cognitive decline. The findings willlay a foundation for scalable, non‐invasive, and mechanism‐driven treatments for ADRD andage‐related memory loss, advancing the broader NIH mission of promoting healthy cognitiveaging.