Gamma Light and Sound Stimulation to Prevent Dementia in Cognitively Normal People at Risk for Alzheimer's Disease

Inclusion criteria

• 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.
• 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.
• Low serum amyloid levels at baseline.
• Elevated fibrillar amyloid using 11C PiB PET at baseline between 20 - 70 CL.
• Willing and able to undergo MRI brain and PET brain scans.
• Adequate visual and auditory acuity to allow for neuropsychological testing.
• Able to comply with neuropsychological testing and other study procedures in opinion of site PI.
• Willing and able to complete baseline assessments, and willing to participate in 13-month study protocol.
• Willing to provide blood samples at specified timepoints. Willing to consider contributing CSF samples at specified timepoints, if asked.

Exclusion criteria

• 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.
• Concomitant medications:
• Treatment with NMDA antagonists.
• For subjects undergoing lumbar puncture, current use of warfarin or similar anti-coagulants is exclusionary for the procedure.
• Clinical conditions:
• History of seizure or medical diagnosis of epilepsy.
• Female subjects who are pregnant or currently breastfeeding.
• History of severe allergic or anaphylactic reactions.
• 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.
• Neurodegenerative disorder associated with cognitive impairment.
• Renal disease.
• 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:
• Severe leukoencephalopathy seen on MRI.
• Relevant structural abnormality (i.e., normal pressure or obstructive hydrocephalus, hypoxic ischemic lesions, hemorrhages, tumors, malformations).
• Cerebral amyloid angiopathy, evidenced by T2\* or other susceptibility weighted-MRI.
• Laboratory findings, if known (study does not perform testing) suggestive of systemic illness such as renal disease.
• 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.