Using light and sound to prevent dementia in at-risk individuals

Prevention of Alzheimer's Disease Using Gamma Entrainment

This study is testing whether a light and sound device can help prevent dementia in people aged 55 and older who have a family history of Alzheimer's by using it daily for a year.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 55 Years to 90 Years
• Sex: All
• Sponsor: Massachusetts General Hospital (other)
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT05776641 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of a light and sound device that stimulates the brain at 40Hz to prevent dementia in cognitively normal individuals aged 55 and older who have a family history of Alzheimer's disease. Participants will use the device at home for 60 minutes daily over 12 months, while undergoing various assessments including PET scans, MRI, EEG, and memory tests at Massachusetts General Hospital. The study aims to determine if this stimulation can reduce amyloid and tau pathology in the brain, potentially improving memory and cognitive function. A total of 200 participants will be recruited, with a subset undergoing additional testing to confirm eligibility based on amyloid deposits.

Who should consider this trial

Good fit: Ideal candidates are cognitively normal adults aged 55-90 with a close family history of Alzheimer's disease and specific eligibility criteria regarding cognitive assessments and amyloid levels.

Not a fit: Patients who do not have a family history of Alzheimer's disease or who do not meet the cognitive and amyloid criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly delay or prevent the onset of Alzheimer's disease in at-risk individuals.

How similar studies have performed: While the approach of using gamma stimulation is novel, preliminary studies in animal models have shown promising results in reducing Alzheimer's pathology.

Eligibility criteria

Inclusion Criteria:

1. Between 55 - 90 years of age, inclusive.
2. Immediate family history of Alzheimer's disease.
3. Mini-Mental State Exam (MMSE) score of 27 or greater at baseline or expected score range for cognitively normal adjusted for education level.
4. Clinical Dementia Rating Global Score of 0 at baseline.
5. Delayed Recall score on the Logical Memory IIa subtest of 8 to 15 at baseline or expected score range for cognitively normal adjusted for education level.
6. Low serum amyloid levels at baseline.
7. Elevated fibrillar amyloid using 11C PiB PET at baseline between 20 - 70 CL.
8. Willing and able to undergo MRI brain and PET brain scans.
9. Adequate visual and auditory acuity to allow for neuropsychological testing.
10. Able to comply with neuropsychological testing and other study procedures in opinion of site PI.
11. Willing and able to complete baseline assessments, and willing to participate in 13-month study protocol.
12. Willing to provide blood samples at specified timepoints. Willing to consider contributing CSF samples at specified timepoints, if asked.

Exclusion Criteria:

1. MRI contraindications, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body.
2. High myopia \< -7 diopters, or untreated cataracts that affect vision.
3. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
4. For subjects agreeing to undergo lumbar punctures, history of bleeding disorders or laboratory results indicating low platelet levels are exclusionary for the procedure.
5. Concomitant medications:

   1. Treatment with NMDA antagonists.
   2. For subjects undergoing lumbar puncture, current use of warfarin or similar anti-coagulants is exclusionary for the procedure.
6. Clinical conditions:

   1. History of seizure or medical diagnosis of epilepsy.
   2. Female subjects who are pregnant or currently breastfeeding.
   3. History of severe allergic or anaphylactic reactions.
   4. 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.
   5. Neurodegenerative disorder associated with cognitive impairment.
   6. Renal disease.
7. MR imaging findings such as stroke, tumor, leukoencephalopathy that could preclude meaningful analyses of clinical and imaging data in the opinion of the site PI, such as:

   1. Severe leukoencephalopathy seen on MRI.
   2. Relevant structural abnormality (i.e., normal pressure or obstructive hydrocephalus, hypoxic ischemic lesions, hemorrhages, tumors, malformations).
   3. Cerebral amyloid angiopathy, evidenced by T2\* or other susceptibility weighted-MRI.
8. Laboratory findings, if known (study does not perform testing) suggestive of systemic illness such as renal disease.
9. Site investigator's discretion, if s/he feels the subject cannot complete sufficient key study procedures. Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the Project Director.

Where this trial is running

Boston, Massachusetts and 1 other locations

• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Massachusetts Institute of Technology — Cambridge, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Diane Chan, MD PhD — Massachusetts General Hospital
• Study coordinator: MJ Quay, MA

Conditions: Alzheimer Disease, Family Members, Cognitively normal, Alzheimer's disease, Gamma, Amyloid