# Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment

> **NIH VA I01** · CENTRAL ARKANSAS VETERANS HLTHCARE SYS · 2020 · —

## Abstract

Background and Objective: One in five older adults has Mild Cognitive Impairment (MCI), a precursor of
dementia. Apathy, a profound loss of initiative and motivation, is seen in as high as 60% of patients with MCI.
Patients with apathy often neglect activities they are fully capable of, related to self-care and physical activity,
which leads to long term impairment and disability. Apathy is associated with impaired executive function,
increased caregiver burden, and higher rates of conversion to dementia. Treatment of apathy in MCI has the
potential to improve the psychological and cognitive health status of Veterans enabling them to function more
fully in society. Apathy treatment may also fundamentally alter the trajectory of neurodegeneration. However,
apathy research sorely lacks: non-pharmacological treatments, objective measurements, biomarkers, and
knowledge whether treatment of apathy improves function, reduces caregiver burden, and decreases
conversion from MCI to dementia. Repetitive transcranial magnetic stimulation (rTMS) applied to the
dorsolateral prefrontal cortex (DLPFC) has yielded promising results in apathy treatment.
The study will examine the efficacy of rTMS treatment on apathy and related measures such as cognition,
functional status, quality of life, and caregiver burden. Lasting effects of these changes during long-term
follow-up will also be examined. An innovation of the proposal is to use a cognitive response from a single
session of rTMS to predict a behavioral response to the longer course of treatment. The study also proposes
to test two promising candidates for validity as biomarkers for apathy research. Finally, the study will explore
if rTMS treatment influences the rates of conversion of MCI to dementia.
Research Plan: A three phase study has been designed. Phase I will consist of comprehensive
assessment and a single session of stimulation in participants eligible for rTMS (N = 75). Phase II will be a
double-blind sham controlled randomized trial of rTMS for apathy (N = 50). Phase III will be a series of
assessments annually till the end of the study to ascertain rates of conversion to dementia (N = 125).
Aim 1 will determine the efficacy and lasting effects of rTMS in treating apathy in MCI compared to sham
treatment. Aim 2 will determine the efficacy and lasting effects of rTMS on cognition, functional status, quality
of life, and caregiver burden compared to sham treatment. Aim 3 will determine the predictive validity of
changes in executive function (Conner's Continuous Performance Test) and biomarker (Brain Derived
Neurotrophic Factor (BDNF)) correlates of apathy after a single session of active rTMS to the overall change
in apathy after 4-weeks of treatment. Aim 4 will compare the rates of conversion of MCI to dementia in those
that received rTMS to sham treatment. This exploratory aim will enable determination of the effect size for
preventing/delaying dementia and serve as the foundation for a larger, m...

## Key facts

- **NIH application ID:** 9816576
- **Project number:** 5I01RX002638-02
- **Recipient organization:** CENTRAL ARKANSAS VETERANS HLTHCARE SYS
- **Principal Investigator:** Prasad R. Padala
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-11-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9816576

## Citation

> US National Institutes of Health, RePORTER application 9816576, Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment (5I01RX002638-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9816576. Licensed CC0.

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