Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits (amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. Gamma waves are important for memory, and in patients with AD, there are fewer gamma waves in the brain. The Tsai lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. A light and sound device was developed for humans that stimulates the brain at 40Hz that can be used safely at home. The goal of this study is to see if using this device can prevent dementia in people who are at risk for developing Alzheimer's disease.
Between 55 - 90 years of age, inclusive.
Immediate family history of Alzheimer's disease.
Mini-Mental State Exam (MMSE) score of 27 or greater at baseline or expected score range for cognitively normal adjusted for education level.
Clinical Dementia Rating Global Score of 0 at baseline.
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.
High myopia < -7 diopters, or untreated cataracts that affect vision.
Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
For subjects agreeing to undergo lumbar punctures, history of bleeding disorders or laboratory results indicating low platelet levels are exclusionary for the procedure.
Parallel
GENUS
DeviceParticipants will use the GENUS light and sound device at home for 60 minutes daily for 12 months
Changes in brain amyloid deposition over the study period, as measured by PiB PET.
The investigators will evaluate changes from baseline in amyloid deposition by using Pittsburgh compound B (PiB) PET, which is a standard for AD trial biomarkers, to assess progression towards AD with active or sham treatment.
Changes in brain tau deposition
The investigators will evaluate changes from baseline in tau deposition by using MK-6240 PET
Changes in brain structure using structural MRI
The investigators will evaluate changes in brain structure using structural MRI. Preliminary data show prevention of brain atrophy after 3 months of GENUS as measured by ventricular dilation and hippocampal volume. Using structural MRI, the investigators will evaluate brain volume, cortical thickness and ventricular volume.
Changes in brain electrical activity
The investigators will evaluate brain electrical activity using longitudinal EEG (ie, gamma band power)
Changes in brain connectivity by functional MRI
The investigators will evaluate connectivity using resting state functional MRI to assess changes in brain networks (ie, default mode network).
Changes in CSF flow, as measured by BOLD fMRI
The investigators will evaluate changes from baseline in CSF flow by using BOLD fMRI. CSF flow has been linked to amyloid clearance from the brain, and brain waste clearance mechanisms such as blood vessel dilation and increased glymphatic drainage are activated after 40-Hz light and sound stimulation in our preliminary mouse studies
Change from baseline in integrity of white matter tracks and myelination as measured by diffusion MR imaging.
It is hypothesized that neuromodulation causes changes in synaptic plasticity. The investigators will evaluate plasticity and structural measures of connectivity using diffusion imaging techniques.
Changes in performance on memory tasks, particularly those that are reliant on visual or auditory pathways, using a neuropsychological test battery.
The investigators will evaluate changes from baseline in performance on memory tasks using a comprehensive neuropsychological battery designed to evaluate pre-clinical AD populations. Preliminary data showed that 3 months of treatment in mild AD patients led to improved performance on an associative memory task.
Change from baseline in gamma oscillations as measured by EEG
Magnetoencephalogram studies done in AD patients show decreases in endogenous gamma synchronization. We will measure induced gamma entrainment using the GENUS device with EEG.
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Massachusetts General Hospital
Lead sponsor
Massachusetts Institute of Technology
Collaborator
