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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy control participants | Active Comparator | Age- and gender matched healthy participant (n=30) with no cognitive problems and normal amyloid PET scan will undergo 48 hour scalp EEG and polysomnography |
|
| Alzheimer disease | Active Comparator | Participants with Alzheimer disease (n=100) will undergo 48 hour scalp EEG and polysomnography |
|
| Alzheimer disease with high seizure risk | Experimental | Selected participants with Alzheimer disease, with higher risk for silent hippocampal seizures after 48 hour scalp EEG and polysomnography (e.g. presence of interictal spikes or frequent nocturnal awakenings) (n=15) will undergo scalp EEG with foramen ovale electrodes with polysomnography |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| scalp EEG and polysomnography | Diagnostic Test | 48 hour 22 channel EEG with polysomnography |
|
| Measure | Description | Time Frame |
|---|---|---|
| Epilepsy | presence of epileptic activity | during EEG recording |
| Sleep wake disorder | presence of sleep wake disorders | during polysomnographic recording |
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Inclusion Criteria:
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.
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:
Participant has a positive amyloid Positron Emission Tomography (PET) scan.
Participant has a Modified Hachinski Ischemic Scale (MHIS) score of ≤ 4.
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:
Participant has evidence of any other clinically significant neurological disorder other than Alzheimer disease, including but not limited to:
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.
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.
Participant has a current diagnosis or history of drug or alcohol abuse (by DSM-V criteria) within 24 months prior to the study.
Participant has a history or evidence of a malignancy within the 2 years prior to the study.
Participant has a known history of Human Immunodeficiency Virus (HIV) infection.
Participant has had surgery under general anesthesia within 3 months prior to the study.
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.
Participant has any history of prior receipt of active immunotherapy directed against tau or amyloid.
Participant is taking anti-epileptic drugs or benzodiazepines.
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.
Subject has any visual, auditory or other impairment that in the Investigator's opinion would preclude collection of outcome measures.
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.
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.
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| Name | Affiliation | Role |
|---|---|---|
| Wim Van Paesschen, MD PhD | UZ and KU Leuven | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Leuven, department of Neurology | Leuven | Vlaams-Brabant | 3000 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24366271 | Background | Ju YE, Lucey BP, Holtzman DM. Sleep and Alzheimer disease pathology--a bidirectional relationship. Nat Rev Neurol. 2014 Feb;10(2):115-9. doi: 10.1038/nrneurol.2013.269. Epub 2013 Dec 24. | |
| 27885006 | Background | Musiek ES, Holtzman DM. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science. 2016 Nov 25;354(6315):1004-1008. doi: 10.1126/science.aah4968. |
| Label | URL |
|---|---|
| Mission Lucidity: Decoding Dementia | View source |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jan 6, 2025 | |
| Reset | Jan 29, 2025 | |
| Release | Mar 26, 2025 | |
| Reset | Apr 17, 2025 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jan 6, 2025 | Jan 29, 2025 | |||
| Mar 26, 2025 |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D004827 | Epilepsy |
| D012893 | Sleep Wake Disorders |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D017286 | Polysomnography |
| ID | Term |
|---|---|
| D008991 | Monitoring, Physiologic |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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The investigators will perform 48-hour ambulatory scalp-EEG and polysomnography in 100 participants with Alzheimer disease and 30 age-and gender-matched healthy participants. The investigators will determine the prevalence of 1.) epileptic discharges and epileptic seizures, 2.) sleep wake disorders and 3.) the interaction of epilepsy and sleep wake disorders in these two groups. A subgroup of 15 of these 100 participants with Alzheimer disease, with interictal epileptic spikes or sleep wake disorders (e.g., frequent nocturnal awakenings) will be invited to undergo an invasive EEG study with foramen ovale electrodes to determine the prevalence of hippocampal seizures, which are usually clinically silent and not detected with scalp EEG.
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| scalp EEG with foramen ovale electrodes with polysomnography | Diagnostic Test | long-term scalp EEG with additional foramen ovale electrodes with polysomnography |
|
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| Apr 17, 2025 |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |