# BDNF-mediated effects of rTMS on cognitive dysfunction in Veterans

> **NIH VA IK2** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2021 · —

## Abstract

Many individuals in our Veteran population, especially the Vietnam era cohort, suffer from dementia-related
cognitive impairment. This number is expected to increase as the population of Veterans age. Developing
effective treatment strategies is of the upmost importance, as this impairment places a huge burden on the
Veterans themselves, their caregivers, and the resources of the Department of Veterans Affairs. Repetitive
transcranial magenetic stimulation (rTMS) is a promising treatment strategy, that utilizes electromagnetics
to noninvasively activate cortical cells and restore cognitive functioning. It is thought that this process
increases neurotrophic signaling throughout the brain, and could potentially increase the integrity of brain
structures sensitive to a loss in neurotrophic factors, especially those structures that declince early in the
course of Alzhiemer's disease (AD).
This proposal aims to improve our understanding of the neurochemistry of cognitive decline, and
subsequently, rehabilitation from rTMS treatment using both human and animal models. We will assess
changes in the neurotrophic factor Brain-Derived Neurotrophic Factor (BDNF) as a result of AD and how
rTMS treatment influences BDNF signaling. The role of this measure will be related to cognitive
performance in both humans and mice. We will first assess the extent of changes in BDNF signaling in a
mouse model of AD, and then we will implement an rTMS system for mice to increase BDNF in the brains of
these mice. This system will be used to test the brain neurochemistry of changes in cognitive function in AD.
Utilization of a mouse model will allow us to comprehensively investigate neurochemistry in a controlled
experimental settting. Specifically, we will measure alterations in the signaling pathway of BDNF in a mouse
model of AD for both rTMS-treated and control mice. We will also determine if rTMS can be utilized to
prevent AD pathology in these mice by providing long-term treatment, and measuring both biochemical
changes and cognitive performance. Finally, BDNF will be measured in blood samples from humans with
cognitive impairment either treated with rTMS or a sham in order to related biochemistry to changes in
human cognitive dysfunction. Exploratory research on key proteins from cerebral spinal fluid and plasma in
humans will pave the way for future funding opportunities in the biochemistry of cognition.
Results from this proposal will provide valuable insight into the biochemical mechanisms of cognitive
decline. This research will also identify key biomarkers that can be related to cognitive performance and be
utilized as concrete measures of treatment outcome. The combination of biochemical and cognitive
measurements on both humans and animals provides an innovative, multi-faceted approach that can be
directly translated into medical treatments for our Veterans.

## Key facts

- **NIH application ID:** 10046296
- **Project number:** 5IK2BX004105-03
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** Margaret Windy McNerney
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046296

## Citation

> US National Institutes of Health, RePORTER application 10046296, BDNF-mediated effects of rTMS on cognitive dysfunction in Veterans (5IK2BX004105-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10046296. Licensed CC0.

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