Memory Enhancement in Aging With Optimal Dosing

Official title

Personalized Memory Enhancement in Aging: Pattern-Optimized tACS With Closed-Loop Precision Modulation

Overview

This project optimizes high-resolution transcranial Alternating Current Stimulation (tACS) to improve memory in healthy older adults, advancing drug-free approaches for Alzheimer's disease and related dementia (ADRD). We test stimulation schedules and develop an adaptive, brain-guided tACS system to strengthen memory-supporting networks.

Detailed description

Cognitive decline, especially in memory and executive control, poses an escalating public health challenge as the population ages, contributing to loss of independence, reduced quality of life, and increased healthcare costs associated with Alzheimer's disease and related 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 schedules that fail to account for individual brain connectivity patterns or dynamic fluctuations in cognitive state.

This project aims to advance precision neuromodulation for cognitive aging by optimizing and personalizing high-resolution tACS protocols to enhance memory in older adults. Building on strong pilot data demonstrating the feasibility of personalized and adaptive stimulation, we will use multimodal imaging (EEG and fMRI) to track changes in frontotemporal synchrony, specifically theta-gamma phase-amplitude coupling and theta phase synchronization, that are known to support memory formation and retrieval.

Aim 1 will establish how stimulation pattern (patterned vs. continuous waveforms) and schedule (one, three, or five consecutive days) shape the durability of memory enhancement. By comparing six systematically varied dosing protocols, we will determine the optimal pattern and repetition schedule that maximize and sustain improvements in working memory capacity, interference control, and long-term memory recognition over one month.

By integrating behavioral, electrophysiological, and neuroimaging measures with adaptive control algorithms, this research will identify reliable biomarkers of responsiveness, elucidate causal mechanisms linking neural synchrony to memory, and yield a new class of personalized, connectivity-guided interventions for cognitive decline. The findings will lay a foundation for scalable, non-invasive, and mechanism-driven treatments for ADRD and age-related memory loss, advancing the broader NIH mission of promoting healthy cognitive aging.

Interventions

• Device 1-day patterned tACS
  Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp with the goal of modulating levels of neuronal excitability.
• Device 3-day patterned tACS
  Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp with the goal of modulating levels of neuronal excitability.
• Device 5-day patterned tACS
  Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp with the goal of modulating levels of neuronal excitability.
• Device 1-day continuous tACS
  Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp with the goal of modulating levels of neuronal excitability.
• Device 3-day continuous tACS
  Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp with the goal of modulating levels of neuronal excitability.
• Device 5-day continuous tACS
  Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp with the goal of modulating levels of neuronal excitability.

Primary outcome measures

• Visual working memory capacity measured behaviorally [Time frame: Baseline, 1-week after intervention, 1-month after intervention]
• Interruption suppression measured behaviorally [Time frame: Baseline, 1-week after intervention, 1-month after intervention]
• EEG phase locking value (PLV) during working memory retention [Time frame: Baseline, 1-week after intervention, 1-month after intervention]
• EEG phase amplitude coupling (PAC) during working memory retention [Time frame: Baseline, 1-week after intervention, 1-month after intervention]

Eligibility criteria

Inclusion criteria

• 65 years of age or older
• normal or corrected-to-normal vision
• color vision

Exclusion criteria

• pregnant
• metal implants in head
• implanted electronic devices
• history of neurological problems or head injury
• skin sensitivity
• claustrophobia
• dementia (normal Montreal Cognitive Assessment > 25)
• depression (normal Geriatric Depression Scale < 10)
• history of psychosis
• cognitive deficits (MoCA>25)
• any psychoactive medication

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Basic science

Study locations

United States · 1 center

• 111 Cummington Mall — Boston

Identifiers

NCT: NCT07461584 · 4230E_3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗