TMS for Cognitive Decline in Aging and Preclinical AD

Grit Against Cognitive Decline in Aging and Preclinical Alzheimer's Disease

In this research study we want to learn more about the effects of non-invasive brain stimulation on motivation, memory, and brain-network function in cognitively unimpaired older adults and individuals with preclinical Alzheimer's disease.

This study will use a form of non-invasive brain stimulation called repetitive Transcranial Magnetic Stimulation (rTMS). rTMS will slightly alter activity in an area of your brain that controls cognition. Changes resulting from this stimulation will be measured with behavioral tests, as well as by taking brain images with Magnetic Resonance Imaging (MRI).

Participants will come in for one baseline visit followed by 10 days of daily rTMS study visits (Monday through Friday) and an evaluation visit. Then, there will be a 2-week break. After this break, they will return for another baseline visit, an additional 10 days of rTMS, and a final evaluation visit.

Study Overview

• Status: Recruiting
• Conditions: Healthy Aging; Cognitive Decline; Prodromal Alzheimer's Disease; Preclinical Alzheimer's Disease
• Intervention / Treatment: Device: Active rTMS; Device: Sham rTMS

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexandra Touroutoglou, PhD; Phone Number: 6176436348; Email: atouroutoglou@mgh.harvard.edu
• Study Contact Backup: Name: Jordan Walter, BA; Phone Number: 6177266207; Email: jwalter2@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Alexandra Touroutoglou, MSc, PhD; Phone Number: 617-643-6348; Email: atouroutoglou@mgh.harvard.edu
      • Principal Investigator: Alexandra Touroutoglou, MSc, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Between the ages of 40-99
2. Native English speakers
3. Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points
4. Cognitively normal older adults and individuals with preclinical Alzheimer's disease will be included.

Exclusion Criteria:

1. History of head trauma involving loss of consciousness or alteration in consciousness
2. Another major neurologic or psychiatric condition
3. Known presence of a structural brain lesion (e.g. tumor, cortical infarct)
4. Any contraindication to MRI, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body
5. Longstanding premorbid history (i.e. longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed
6. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
7. Unwilling to return for follow-up, undergo neuropsychological testing, TMS, and MR imaging
8. History of unprovoked seizures (i.e., seizures that occur in the absence of a clear provocation such as hyponatremia, hypoglycemia, etc.).
9. Subjects who have a first degree relative (e.g., father, mother or sibling) with a seizure disorder.
10. Subjects currently taking, or plan to take, medications which are highly epileptogenic. These include: clozapine, high doses of bupropion (i.e., greater than 400mg daily), diphenhydramine, cyclosporine, isoniazid, imipenem, chloroquine, tramadol and theophylline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active TMS; All participants will receive the same study interventions in a within-subject crossover design.	Device: Active rTMS; All study participants will receive one block of ACTIVE rTMS. Each block will consist of daily sessions of active rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).
Sham Comparator: Sham TMS; All participants will receive the same study interventions in a within-subject crossover design.	Device: Sham rTMS; All study participants will receive one block of SHAM rTMS. Each block will consist of daily sessions of SHAM rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in motivation	This will be measured by ratings of grit on a 5-point scale using the Grit Scale (Duckworth, et al., 2007).	Baseline and post-treatment Day 11
Changes in Brain Network Connectivity	This will include changes in resting-state functional connectivity measured with functional Magnetic Resonance Imaging (fMRI)	Baseline and post-treatment Day 11
Changes in Memory	This will be measured with an associative memory task	Baseline and Post-Treatment Day 11

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: April 14, 2025
• First Submitted That Met QC Criteria: May 1, 2025
• First Posted (Actual): May 4, 2025

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 2023A009489

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No