Alzheimer Disease, Alzheimer Disease, Early Onset, Dementia
Conditions
Keywords
Stimulation, Nucleus Basalis, Alzheimer, Memory
Brief summary
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.
Interventions
PROCEDUREDevice Implantation- Boston Scientific, VERCISE GENUS™ system
Participants will be implanted with DBS leads bilaterally, targeting the Nucleus Basalis of Meynert. The study team will record Local Field Potentials with and without stimulation, intraoperatively. These results will help the team determine at the end of the study whether LFP desynchronization (decrease in 5-15 Hz power), or other physiological signature, can be used to predict the location that provides the most effective intervention. Finally, the team will also ascertain the safety of the procedure and NB stimulation itself.
DEVICEDBS Stimulation - Boston Scientific, VERCISE GENUS™ system
Daily intermittent stimulation (60 Hz x 20s/min)
Sponsors
Vanderbilt University Medical Center
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a feasibility study to 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 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. Intermittent stimulation will be delivered at 60 pulses per second for 20 seconds of each minute for one hour per day. The study design will test the safety and feasibility 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.
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Dementia Rating score change | 12 - 24 Months | . The primary outcome indicating success will be an increase in the mean score of the Clinical Dementia Rating - Sum of Boxes of the pre-stimulation baseline that is equal or greater than the increase in the post-stimulation data by 1 point or more, after 12-36 months of stimulation. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDave Blake, PhD
Augusta University
PRINCIPAL_INVESTIGATORDario Englot, MS, PhD, MD
Vanderbilt University Medical Center
Outcome results
None listed