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

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 scorerange 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 orexpected 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 opinionof 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 considercontributing CSF samples at specified timepoints, if asked.

Exclusion Criteria:

1. MRI contraindications, such as presence of pacemakers, aneurysm clips, artificialheart 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 todifficulty complying with the study protocol.

4. For subjects agreeing to undergo lumbar punctures, history of bleeding disorders orlaboratory results indicating low platelet levels are exclusionary for theprocedure.

5. Concomitant medications:

6. Treatment with NMDA antagonists.

7. For subjects undergoing lumbar puncture, current use of warfarin or similaranti-coagulants is exclusionary for the procedure.

8. Clinical conditions:

9. History of seizure or medical diagnosis of epilepsy.

10. Female subjects who are pregnant or currently breastfeeding.

11. History of severe allergic or anaphylactic reactions.

12. Longstanding premorbid history (i.e., longer than 10 years) of alcohol orsubstance abuse with continuous abuse up to and including the time that thesymptoms leading to clinical presentation developed.

13. Neurodegenerative disorder associated with cognitive impairment.

14. Renal disease.

15. MR imaging findings such as stroke, tumor, leukoencephalopathy that could precludemeaningful analyses of clinical and imaging data in the opinion of the site PI, suchas:

16. Severe leukoencephalopathy seen on MRI.

17. Relevant structural abnormality (i.e., normal pressure or obstructivehydrocephalus, hypoxic ischemic lesions, hemorrhages, tumors, malformations).

18. Cerebral amyloid angiopathy, evidenced by T2* or other susceptibilityweighted-MRI.

19. Laboratory findings, if known (study does not perform testing) suggestive ofsystemic illness such as renal disease.

20. Site investigator's discretion, if s/he feels the subject cannot complete sufficientkey study procedures. Exceptions to these guidelines may be considered on acase-by-case basis at the discretion of the Project Director.