Cholinergic Deep Brain Stimulation for Alzheimer's Disease

Inclusion criteria

• Probable, early-stage AD, as defined by NIA-AA 2018 criteria, including amnestic Mild Cognitive Impairment (MCI)

• Clinical Dementia Rating (CDR) global score of 0.5-1.0 with a memory box score of at least 0.5
• MMSE ³ 23
• Stable cognitive enhancer medication equivalent to 10 mg/day donepezil or less for at least 60 days
• Stable other medications (e.g., psychotropics)
• Valid informed consent if female, subjects who are post-menopausal or surgically sterile or willing to use birth control methods for the duration of the study
• an available caregiver willing to participate
• subject is living at home and likely to remain at home for the study duration.

Exclusion criteria

• Active or unstable psychiatric illness
• Inability to tolerate general anesthesia.
• Another concurrent CNS condition or clinical co-morbidity interfering with the study (ie, stroke, Parkinson's disease, Lewy-Body dementia or other form of dementia, other evidence of significant structural brain pathology).
• Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit
• Verbal IQ<85
• Contraindication regarding anesthesia, stereotactic operation, MRI (e.g. claustrophobia, or implants), or PET (e.g. insulin dependent diabetes) procedures
• Inability to undergo PET or MRI imaging
• Active alcohol or substance abuse as defined by DSM5
• Is unable or unwilling to comply with protocol follow-up requirements
• Is actively enrolled in another concurrent clinical trial.
• Terminal illness associated with expected survival of <12 months