TMS for Cognitive Decline in Aging and Preclinical AD

NCT06956300 | Recruiting DMC FDA Device

• 1 other identifier: 2023A009489
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prodromal Alzheimer's Disease; Preclinical Alzheimer's Disease; Healthy Aging; Cognitive Decline

Keywords

Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Active TMS

EXPERIMENTAL

All participants will receive the same study interventions in a within-subject crossover design.

Device: Active rTMS

Sham TMS

SHAM COMPARATOR

All participants will receive the same study interventions in a within-subject crossover design.

Device: Sham rTMS

Interventions

Active rTMS DEVICE

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).

Active TMS

Sham rTMS DEVICE

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).

Sham TMS

Eligibility Criteria

• Age: 40 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• History of head trauma involving loss of consciousness or alteration in consciousness
• Another major neurologic or psychiatric condition
• Known presence of a structural brain lesion (e.g. tumor, cortical infarct)
• 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
• 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
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
• Unwilling to return for follow-up, undergo neuropsychological testing, TMS, and MR imaging
• History of unprovoked seizures (i.e., seizures that occur in the absence of a clear provocation such as hyponatremia, hypoglycemia, etc.).
• Subjects who have a first degree relative (e.g., father, mother or sibling) with a seizure disorder.
• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Alexandra Touroutoglou, PhD

CONTACT

6176436348; atouroutoglou@mgh.harvard.edu

Jordan Walter, BA

CONTACT

6177266207; jwalter2@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: May 4, 2025
• Study Start: April 7, 2025
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)