Prevalence of Epilepsy and Sleep Wake Disorders in Alzheimer Disease

Alzheimer disease is the most common of the neurodegenerative diseases. Epilepsy and sleep wake disorders are co-morbid conditions of Alzheimer disease. The investigators propose a prospective study using long-term EEG monitoring in combination with polysomnography to determine prevalence of epilepsy and sleep wake disorders in Alzheimer disease, and correlate these findings with clinical data, Alzheimer disease biomarkers and imaging studies (MRI and amyloid/tau-PET). In selected patients, the investigators will perform EEG studies with foramen ovale electrodes. The ultimate goal is to improve the outcome of patients with Alzheimer disease by early treatment of epilepsy and restoring sleep-wake disturbances.

Alzheimer disease is the most common of the neurodegenerative diseases. Epilepsy and sleep wake disorders are co-morbid conditions of Alzheimer disease, and there is evidence to suggest that the interactions are bidirectional. Neuronal activity promotes the production and secretion of amyloid β, which could actually drive pathogenesis early in the course of Alzheimer disease, and has been described in sleep wake disorders and epilepsy. Epileptic seizures in Alzheimer disease are often subtle, nocturnal and easily overlooked. We propose a prospective study using long-term EEG monitoring in combination with polysomnography to diagnose epilepsy and sleep wake disorders in Alzheimer disease, and correlate these findings with clinical data, Alzheimer disease biomarkers and imaging studies (MRI and amyloid/tau-PET). It is the hypothesis of the investigators that participants with Alzheimer disease and interictal spikes or specified sleep wake disorders (e.g., frequent nocturnal awakenings) during 48 hour scalp EEG and polysomnography are at risk for having hippocampal seizures, which are often clinically silent and not detected on scalp EEG. The investigators will invite 15 of these participants to undergo EEG studies with foramen ovale electrodes to determine the prevalence of these hippocampal seizures. The ultimate goal is to improve the outcome of patients with Alzheimer disease by early treatment of epilepsy and restoring sleep-wake disturbances.

Eligibility Criteria:
Inclusion Criteria:

1. Participant must be able to understand the nature of the study and has the opportunity to have any questions answered. The participant has voluntarily signed the independent Review Board (IRB)/independent Ethics Committee (IEC) approved Informed Consent, prior to the conduct of any study procedures. If the participant is not fully competent, full informed consent must be obtained from a representative and assent must be obtained from the participant.
2. Participant who meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) clinical criteria for mild cognitive impairment or probable Alzheimer Disease, and have:

   * Clinical Dementia Rating (CDR)-Global Score of 0.5
   * A Mini-Mental State Examination (MMSE) score of 22 to 30
   * Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index (RBANS-DMI) score of 85 or lower
3. Participant has a positive amyloid Positron Emission Tomography (PET) scan.
4. Participant has a Modified Hachinski Ischemic Scale (MHIS) score of ≤ 4.
5. Participant has an identified, reliable, study partner (e.g., family member), who has frequent contact with the participant and who will provide information as to the participant's cognitive and functional abilities.

Exclusion Criteria:

1. Participant has evidence of any other clinically significant neurological disorder other than Alzheimer disease, including but not limited to:

   * Parkinson's disease
   * vascular dementia
   * significant cerebrovascular abnormalities
   * frontal-temporal dementia
   * Huntington's disease
   * normal pressure hydrocephalus
   * brain tumor
   * progressive supranuclear palsy
   * seizure disorder
   * subdural hematoma
   * multiple sclerosis
   * history of significant head trauma followed by persistent neurologic deficits
   * known structural brain abnormalities
   * obstructive sleep apnea syndrome treated with continuous positive airway pressure (CPAP)
2. Participant has a screening MRI scan, interpreted by a radiologist with evidence of infection, infarction (including multiple lacunas in a critical memory structure), or other focal lesions.
3. Participant has a history of or currently has schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-V or International Classification of Diseases (ICD)-10 criteria.
4. Participant has a current diagnosis or history of drug or alcohol abuse (by DSM-V criteria) within 24 months prior to the study.
5. Participant has a history or evidence of a malignancy within the 2 years prior to the study.
6. Participant has a known history of Human Immunodeficiency Virus (HIV) infection.
7. Participant has had surgery under general anesthesia within 3 months prior to the study.
8. Receipt of an investigational product within a time period equal to 5 half-lives, if known, or within 6 weeks (for small molecules) or 6 months (for monoclonal antibodies or other biologics) prior the study.
9. Participant has any history of prior receipt of active immunotherapy directed against tau or amyloid.
10. Participant is taking anti-epileptic drugs or benzodiazepines.
11. Participant has an abnormally low vitamin B 12 (cobalamin), abnormal thyroxine (T4) or an abnormally high thyroid stimulating hormone (TSH) that is considered clinically significant by the investigator.
12. Subject has any visual, auditory or other impairment that in the Investigator's opinion would preclude collection of outcome measures.
13. In the opinion of the investigator, the subject has any clinically significant or uncontrolled medical or psychiatric illness, or has had an infection requiring medical intervention in the past 30 days.
14. Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions (e.g., coronary artery bypass graft, percutaneous coronary intervention via cardiac catheterization, thrombolytic therapy), within 6 months of the study.