Neuropsychological investigation, lumbar puncture, long term-EEG monitoring and/or MEG-EEG, magnetic resonance imaging (MRI), blood sample with deep genetic profiling and Apolipoprotein E (APOE) determination.

Neuropsychological investigation, lumbar puncture, long term-EEG monitoring and/or MEG-EEG, MRI, blood sample with deep genetic profiling and APOE determination.

Mild Cognitive Impairment

Alzheimer Disease

Lumbar puncture for AD biomarker fluid analysis

Lumbar puncture

UZ Brussel

Epilepsy in Alzheimer's Disease: Effect on Disease Progression

Comparison of prevalence of subclinical epileptiform activity (measured by LTM-EEG and MEG)

Odds ratio of conversion (measured by neuropsychological examination).

Universitair Ziekenhuis Brussel

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

Participants with Alzheimer disease (n=100) will undergo 48 hour scalp EEG and polysomnography

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

Alzheimer Dementia

Epilepsy

Sleep Wake Disorders

48 hour 22 channel EEG with polysomnography

scalp EEG and polysomnography

long-term scalp EEG with additional foramen ovale electrodes with polysomnography

scalp EEG with foramen ovale electrodes with polysomnography

University Hospitals Leuven, department of Neurology

Prevalence of Epilepsy and Sleep Wake Disorders in Alzheimer Disease

Prof Dr W Van Paesschen

Professor Doctor

Universitaire Ziekenhuizen Leuven

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.

Excitation Paradigm: LIFUP excites the activity of hippocampal neurons.

Inhibition Paradigm: LIFUP inhibits the activity of hippocampal neurons.

Brain Imaging

Deep Brain Stimulation

Administration of LIFUP, a method of deep brain stimulation, according to excitation paradigms using the following parameters: Tone Burst Duration = 50ms; Pulse Repetition Frequency = 10Hz; ISPTA = 720 mW/cm2. Four treatments of thirty seconds each, with two-minute intervals between treatment (20 minutes, approximately)

Excitation

Administration of LIFUP, a method of deep brain stimulation, according to inhibition paradigms using the following parameters: Tone Burst Duration = 50ms and Pulse Repetition Frequency = 10Hz. Four treatments of thirty seconds each, with two-minute intervals between treatment (20 minutes, approximately)

Inhibition

American Institute of Ultrasound in Medicine. Official statement on "Safety in training and research."

Analysis Group, Oxford, UK. FMRIB Software Library v5.0.

MathWorks. The language of technical computing.

UCLA Longevity Center

Deep Brain Stimulation With LIFUP for Mild Cognitive Impairment and Mild Alzheimer's Disease

Study of Non-Invasive Deep Brain Stimulation With Low Intensity Focused Ultrasound Pulse (LIFUP) for Mild Cognitive Impairment (MCI) and Mild Alzheimer's Disease (AD)

Functional MRI of the brain will be obtained throughout the LIFUP session for the purposes of image acquisition.

The Hopkins Verbal Learning Test-Revised will provide a measure of verbal memory. It requires recall of a series of 12 words over three learning trials, free recall after a 25-minute delay, and a recognition trial. There are 6 equivalent alternate forms.

The Brief Visual Memory Test-Revised will provide a measure of visual memory. In three learning trials, the respondent views 6 geometric figures for 10 seconds and is asked to draw as many of the figures as possible from memory in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Last, a Recognition Trial, in which the respondent is asked to identify which of 12 figures were included among the original geometric figures, is administered. There are 6 equivalent alternate forms.

Geriatric Anxiety Inventory (GAI) will be used as a measure to ensure that pre-LIFUP/pre-MRI anxiety is not significantly impacting performance on the first neuropsychological assessment.

Gary Small, MD

Professor of Psychiatry and Biobehavioral Sciences

University of California, Los Angeles

Participants will be randomly assigned to one of two LIFUP pulsing paradigms: one that excites the activity of hippocampal neurons ("Paradigm A"), or a second that inhibits them ("Paradigm B"). The participants will then be administered four successive LIFUP treatments while the participants are in a functional magnetic resonance imaging (MRI).

Participants and the participants' caregivers will be blinded to arm assignment.

Patients older than 60 years, with normal brain MRI and with normal cognitive functioning who demonstrate a profile of CSF biomarkers of AD suggestive of biological AD

profile of CSF biomarkers of AD

Hospices Civils de Lyon

CHU Gabriel- Montpied

CHU des Alpes

CHU Hôpital Nord

Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy

Evolution of RL/RI-16 score between inclusion and 2 years of follow-up

Evolution of DMS 48 score between inclusion and 2 years of follow-up

Evolution of semantic memory at 2 years: Evolution of DO 80 score between inclusion and 2 years follow-up

Evolution of semantic memory at 2 years: Evolution of categorical influences between inclusion and 2 years follow-up

Evolution of semantic memory at 2 years: Evolution of TOP 10 score between inclusion and 2 years follow-up

Evolution of monthly frequency of seizures between inclusion and 2 years of follow-up

Any pregnant women that is referred to or presents to our tertiary care facility with concern for preeclampsia, will have a Congo Red Dot test preformed by research nurses. The research nurses are not involved in patient management and the results are blinded to the clinical providers and have no impact on clinical diagnosis or patient management.

Preeclampsia

The Ohio State Medical Center Labor and Delivery Unit

The Clinical Utility of the Congo-Red Dot Test for Diagnosis and Early Prediction of Preeclampsia During Pregnancy

Diagnostic utility of the test based on AUC

amyloid/seizures

Epilepsy in Alzheimer's Disease: Effect on Disease Progression

Prevalence of Epilepsy and Sleep Wake Disorders in Alzheimer Disease

Deep Brain Stimulation With LIFUP for Mild Cognitive Impairment and Mild Alzheimer's Disease

Predictive Value of Biomarkers of the Alzheimer's Disease (AD) in Elderly Patients With New-onset Epilepsy

The Clinical Utility of the Congo-Red Dot Test for Diagnosis and Early Prediction of Preeclampsia During Pregnancy

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