Cholinergic Deep Brain Stimulation for Alzheimer's Disease

This project will investigate the potential of Deep Brain Stimulation to improve cognitive abilities and counteract the effects of Alzheimer's disease. Deep Brain Stimulation electrodes targeting the Nucleus Basalis of Meynert (NB) will be implanted bilaterally in a cohort of patients. NB is the sole source of acetylcholine to the neocortex. Such stimulation may not only treat the cognitive symptoms but may have disease-modifying effects. Drawing from animal experiments in non-human primates that showed success of this approach, intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute for one hour per day. The study team will recruit patients, shortly after first being diagnosed with Alzheimer's disease. The study design will test the safety and efficacy of stimulation, potential benefits in cognitive function assessed with a battery of neurocognitive tests, cholinergic neurotransmission evaluated with Positron Emission Tomography, and ability to reverse Alzheimer's biomarkers, including beta amyloid and tau in the cerebrospinal fluid. Successful completion of this project will lead to a potential new intervention for the cognitive impairments of 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\