Deep Brain Stimulation Guided by Brain Mapping to Treat Cognitive Impairment

Prior treatment

• Participation in another drug, device, or biological study within 90 days.
• Any clinical impression reflective of disease pathologies indicated by the list below is exclusionary
  • Frontotemporal degeneration spectrum disorders (e.g., behavioral-variant FTD, primary progressive aphasia)
  • Dementia with Lewy bodies / Parkinson disease dementia
  • Cerebral amyloid angiopathy (moderate to severe)
  • Eligibility Note:
  • Participants will be excluded if the investigator determines that cognitive impairment is primarily attributable to vascular cognitive impairment, Lewy body disease, frontotemporal degeneration, Parkinson's disease, traumatic brain injury, delirium, unstable psychiatric illness, medication effects, substance use, or another non-AD neurologic or systemic condition.
  • A prior or concurrent diagnosis of Alzheimer's disease is permitted only if the participant is clinically at the MCI / mild neurocognitive disorder stage, rather than dementia stage. In other words, participants with "MCI due to Alzheimer's disease," "prodromal Alzheimer's disease," or "early Alzheimer's disease" may be included if functional independence is preserved.

Other illness

• Active alcohol or substance use disorder within 6 months of entering the Screening Phase, excluding nicotine. Urine drug test positive for illicit drugs.
• Neurological/Medical condition that makes the participant, in the opinion of the surgeon, a poor surgical candidate (e.g., progressive neurodegenerative disorder, significant cardiopulmonary disorder, need for chronic anticoagulation).
• Any history of seizure disorder, hemorrhagic stroke, or has high risk of seizure (history of congenital brain malformation, neuro-developmental disorder , or other factors that predispose seizures such as an active eating disorder).
• Cognitive symptoms that are not be better explained by delirium, unstable psychiatric illness, active substance use disorder, major untreated sleep disorder, acute neurologic illness, or other medical condition that, in the investigator's judgment, is the primary cause of the impairment.
• Brain structural MRI abnormalities outside of expected pathology associated with Mild Cognitive Impairment.
• Any medical contraindication to surgery such as infection.
• Uncontrolled hypertension (systolic \> 145mmHg and/or diastolic \> 90 mmHg), demonstrated on each of three repeated measurements taken within one hour regardless of whether or not the participant is taking antihypertensive medications.
• Any Psychiatric/Neurological/Medical condition that makes the participant, in the opinion of the Investigator, a poor candidate. These may be but are not limited to a DSM-5 diagnosis of schizophrenia, bipolar disorder, obsessive-compulsive disorder.
• A separate cardiac condition that, in the opinion of a study physician, would present an unacceptable risk of undergoing general anesthesia.

Lab values

• Coagulopathy: Bleeding propensity and/or one of the following: INR \> 1.5; prolonged activated partial thromboplastin time (aPTT) ≥ 45 sec; platelet count \< 100×103 /uL
• Chronic use of anticoagulant or anti-platelet agents that cannot be safely stopped for a sufficient duration (minimum 2.5 weeks) in the peri-operative period.

Other

• Current implanted neural stimulation devices including spinal cord stimulators and deep brain stimulators.
• Need for Diathermy.
• Moderate to severe depressive symptoms, defined as a GDS-15 score ≥11 at screening, or investigator judgment that depressive symptoms are unstable, severe, or likely to interfere with study participation or interpretation of cognitive outcomes.
• High risk of suicide, defined as any of the following on the Columbia Suicide Severity Rating Scale (C-SSRS) short form at screening: active suicidal ideation with intent to act, active suicidal ideation with a specific plan and intent, suicidal behavior within the past 3 months or investigator judgment that the participant is at imminent or clinically significant risk for self-harm.

• Men and women (non-pregnant) between ages 60 and 85.
• Meets NIA-AA core clinical criteria for MCI due to Alzheimer's Disease.
• Determination by the investigator, based on clinical judgment and review of medical history, neurological examination, cognitive profile, and available clinical data, that Alzheimer's Disease is the primary suspected etiology.
• Absence of other psychiatric or physical conditions that could interfere with the study.
• Stable medication regimen for 4 weeks preceding surgery; participants currently receiving anti-amyloid therapies may enroll if they are able and willing to pause infusions for at least 12 weeks prior to study initiation and for the duration of the study.
• Other medical conditions must be stable for at least 6 months prior to SEEG Implantation.
• Able and willing to give informed consent or have a Legally Authorized Representative who is able to sign the informed consent form.
• Able to have a study partner(s) or close relative(s) present for discussions about the study