# Noninvasive Cortical Stimulation to Improve Memory in Mild Cognitive Impairment

> **NIH NIH R01** · PALO ALTO VETERANS INSTIT FOR RESEARCH · 2021 · $59,537

## Abstract

Abstract: Mild Cognitive Impairment (MCI) carries a high risk of progression to dementia due to Alzheimer's
disease (AD). Yet, there are currently no effective treatments. For older adults with MCI, the cognitive
problems and uncertainty they face negatively impacts their everyday functioning, capacity and confidence to
engage in challenging cognitive activities, and thus their quality of life. A substantial proportion of adults with
MCI either take cholinesterase inhibitors or have tried them, but the low efficacy of these approved treatments
for AD appears outweighed by their side effects.
The goal of this study is to test the efficacy of a non-pharmacological treatment for MCI that involves
noninvasive brain stimulation (NIBS). Early studies in AD dementia patients have found that repetitive
transcranial magnetic stimulation (rTMS, a form of NIBS) improved global cognitive function and activities of
daily living. Given that in AD, neuronal loss and synaptic dysfunction progress along brain networks, these
early studies of brain stimulation in AD dementia suggest there is sufficient neuroplasticity for efficacious
effects of brain stimulation. Of the very few rTMS studies in MCI that have been published, the effect size
appears to be moderately large. However, it is not clear whether the dorsolateral prefrontal cortex (DLPFC),
the stimulation site used in most of the prior MCI/AD rTMS trials, is the optimal site for achieving the most
efficacious effects including effects on episodic memory. Importantly, when other investigators used rTMS to
stimulate a lateral parietal cortical (LPC) site in healthy young adults, significant effects of rTMS on memory
were measurable weeks later. Moreover, functional connectivity of brain regions was selectively increased,
including the posterior cingulate cortex (PCC), a “hub” of brain networks that is affected in amnestic MCI.
Because stimulation of the DLPFC and the LPC may each have distinct effects, we designed this pilot trial to
have two active rTMS treatment groups: DLPFC and LPC. A third group, a sham-control, will also be included
to achieve a controlled, randomized, double-blind trial. For each of the three groups, stimulation will be
bilateral, based on effects achieved in the AD studies. The primary hypothesis is that active rTMS (to either
site of stimulation) will be superior to sham-control in improving memory. Measures of change in functional
connectivity will be computed to examine whether there is evidence that rTMS changes connectivity of the
PCC with other regions of the brain. In addition to looking at effects of rTMS on functional connectivity and
cognition in relation to the cortical site stimulated, genetic markers will be collected toward addressing
heterogeneity of response. To track the durability of rTMS effects on memory, participants will be followed
longer than in any prior study (up to 6 months after the intervention). If this study finds rTMS improves memory
in older adults wit...

## Key facts

- **NIH application ID:** 10144899
- **Project number:** 5R01AG055526-04
- **Recipient organization:** PALO ALTO VETERANS INSTIT FOR RESEARCH
- **Principal Investigator:** JOY L TAYLOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $59,537
- **Award type:** 5
- **Project period:** 2017-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144899

## Citation

> US National Institutes of Health, RePORTER application 10144899, Noninvasive Cortical Stimulation to Improve Memory in Mild Cognitive Impairment (5R01AG055526-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144899. Licensed CC0.

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