Deep Brain Stimulation in Alzheimer's Disease: Biomarkers and Dose Optimization

Prior treatment

• The subject has attempted suicide in the 2 years prior to signing the consent to participate in the study.
• History of head trauma in the 2 years prior to signing the consent to participate in the study
• Radiation exposure in the 1 year prior to signing the informed consent form that, in combination with the radiation exposure from this study, would exceed 5 rem.
• Currently prescribed any non-AD medications that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
• Is actively enrolled in another concurrent clinical trial.

Other illness

• Cornell Scale for Depression and Dementia (CSDD) score \> 10 at the screening visit
• Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit
• History of brain tumor, subdural hematoma, or other clinically significant (in the judgment of the investigator) space-occupying lesion on CT or MRI
• Active psychiatric disorder
• Current alcohol or substance abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
• Contraindications for PET scanning (e.g., insulin dependent diabetes)
• Contraindications for MRI scanning, including implanted metallic devices (e.g. non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces.
• Abnormal cardiovascular or neurovascular disorder that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
• Unstable dose of any medication prescribed for the treatment of memory loss or Alzheimer's disease.

Other

• Neuropsychiatric Inventory (NPI) total score ≥ 10 or score ≥ 4 in any NPI domain (clinically significant neuropsychiatric symptoms). Apathy score ≥ 4 acceptable.
• Subjects at risk for suicide in the opinion of the investigator or the subject answers "yes" to "Suicidal Ideation" Item 4 or 5 on the C-SSRS (at time of evaluation) at the screening or baseline visit.
• Young Mania Rating Scale (YMRS) ≥ 11 at the screening visit
• In the judgment of the investigator, the subject is at significant risk for suicidal behavior during the course of his/her participation in the study
• Mental retardation
• Abnormal lab results that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
• Is unable or unwilling to comply with protocol follow-up requirements.
• Has a life expectancy of \< 1 year.

• Informed consent signed by the subject AND a reliable caregiver
• 45-85 years of age (inclusive)
• Probable Alzheimer's disease according to the National Institute of Aging Alzheimer's disease Association criteria.
• Clinical Dementia Rating (CDR) global rating of 0.5 or 1 at screening.
• ADAS-cog-11 score of 12-30 inclusive at screening AND baseline (with a score ≥ 4 on ADAS-cog item 1) or a Mini Mental State Examination (MMSE) of 16-28.
• If female, post-menopausal, surgically sterile or willing to use birth control methods for the duration of the study.
• The patient has an available caregiver or other appropriate knowledgeable informant who can reliably report on daily activities and function and signs the informed consent for participation as such.
• Patient is living at home and likely to remain at home for the study duration.
• General Medical Health Rating (GMHR) ≥ 3 (good or excellent general health).
• Patient must be a good surgical candidate for placement of a deep brain stimulator as judged by the DBS surgical team.
• Fluency (oral and written) in the language in which standardized tests will be administered.
• The patient is taking a stable dose of cholinesterase inhibitor (AChEI) medication (donepezil, galantamine, or rivastigmine) for at least 60 days prior to signing the informed consent form and there is no intention to modify the dose over the course of the study (NOTE: These medications may NOT be initiated, discontinued or modified after study initiation for the length of study participation).