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. The investigator's 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. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. For the present study, 60 participants with mild Alzheimer's disease will be enrolled and will use this light and sound device at-home daily for 6-months. Investigators will measure changes in brain waves with EEG, blood biomarkers, the microbiome via fecal samples, functional and structural MRI scans, memory and cognitive testing, and questionnaires at 3 in-person visits throughout the study. After the 6-month time point, participants will have the option of continuing in the study for at least one year and completing yearly study visits. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.
Subject is between the ages of 65 - 100.
Subject must have mild Alzheimer's disease with a Mini Mental State Exam (MMSE) score of 19-26.
Subject is willing to sign informed consent document.
If subject is deemed to not have capacity to sign the informed consent, he/she will need a legally authorized representative to provide surrogate consent.
Subjects who do not have healthcare.
Subjects who are currently taking amyloid reducing therapy.
Subjects who have > 4 cerebral microbleeds or 1 macrobleed in their brain
Active treatment on a dosage of one or more psychiatric agents (e.g. antidepressants, antipsychotics, etc) for LESS THAN three months (a stable dose for greater than or equal to three months is ok).
Parallel
GENUS device (Active Settings)
DeviceParticipants in the active, experimental group will use the GENUS devices configured to active (40Hz) setting for 60 minutes daily for 6 months.
GENUS device (sham settings)
DeviceParticipants in the control group will use the GENUS devices configured to the sham settings for 60 minutes daily for 6 months.
Feasibility of gamma frequency stimulation as assessed by a change of gamma frequency waves during EEG
Feasibility of gamma frequency stimulation in subjects with AD will be assessed by analyzing the EEG data from each subject as they undergo gamma light, sound, and tactile stimulation. Investigators will look for a sign of change in gamma frequency waves and determine the percent of subjects who show this change. This change will be assessed through FFT analyses on the EEG data in MATLAB, which looks at the different frequencies that were present during the EEG session.
Baseline incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Mid-point incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Endpoint incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Changes in the microbiome as measured by fecal samples
At baseline and month 6, subjects will produce a fecal sample and hand it off to study staff for storage and sample processing using the QIAamp PowerFecal Pro DNA Kit (Qiagen). Data will then be analyzed using the Divisive Amplicon Denoising Algorithm 2 (DADA2) pipeline, which will provide gut microbial composition in the different experimental groups. Pipeline outputs involve principal component analyses, and a custom in-house script will be used to make statistical comparisons. Change will be assessed by comparing the fecal sample analyses between baseline and month 6.
Changes in cognitive performance as assessed by scores on an Alzheimer's cognitive testing battery
Exploratory measure to check if there is any change in cognitive performance as a result of 6 months of daily sessions with the light and sound device. Alzheimer's testing battery will be administered at baseline, month 3, and month 6 visits, and change will be determined by comparing cognitive performance (via standardized scores) at these three timepoints. These tests measure a variety of cognitive abilities, including attention, different types of memory, processing speed, visual acuity, and more.
Changes in sleep/wake patterns, as measured by actigraph watch analyses
Subjects will be expected to wear a GTX9 actigraph watch daily to record activity and sleep/wake patterns throughout the 6-months of the trial. This watch is like a regular wrist watch, but it records daily activity and patterns through light and movement. The subject will be given their watch \~2 weeks before the trial start-date, and they will bring it in with them at baseline, month 3, and month 6 visits so researchers can download their data to analyze their length and quality of sleep, as well as their other circadian rhythms and patterns throughout each day. Change will be assessed by comparing actigraph data between baseline, month 3, and month 6, as subject progress throughout the trial.
Click on the lead sponsor to view all of their trials.
