Alzheimer Disease, Lewy Body Dementia (LBD), Mild Alzheimer Disease, Frontotemporal Dementia (FTD), Mild Cognitive Impairment (MCI), Healthy Subjects
Conditions
Keywords
high-definition electroencephalogram, Brain Magnetic Resonance Imaging, Biomarker profile, Positron Emission Tomography, Apolipoprotein E, Mild Cognitive Impairment, Frontotemporal dementia, Lewy-body dementia, Dementia
Brief summary
The study aims to use advanced brainwave recordings of electroencephalogram (EEG) to understand early signs of Alzheimer's disease (AD) in people with mild memory problems, known as amnestic Mild Cognitive Impairment (MCI). The goals of the study are to: 1. Find early markers of Alzheimer by analyzing EEG recordings, the researchers hope to identify patterns that indicate the presence of Alzheimer's disease. They will compare these patterns with other brain scans, like Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scans, and look at different biological markers in the participants' spinal fluid and genetic data. 2. Predict the risk of Alzheimer's disease. The study will try to find EEG patterns that can predict whether someone with MCI will develop full-blown Alzheimer's disease. The aim is to create a system that combines EEG data with other brain scans and genetic information to better understand the risk of disease progression. 3. Track changes over time: The research will also monitor changes in brain activity and structure over time to understand how Alzheimer's disease progresses. In addition to studying people with MCI, the researchers will also look at EEG patterns in people with mild Alzheimer's disease (MILD AD), frontotemporal dementia (FTD), and Lewy-body dementia (LBD) to see how these patterns differ across various brain conditions. This could help improve the accuracy of diagnosing these diseases and understanding their link to genetic factors.
Detailed description
The main aim of the project is to examine resting-state high definition EEG cortical sources of participants diagnosed with amnestic MCI with the goal of: \- exploring EEG-markers of Alzheimer's disease pathology and their relationships with both conventional and non-conventional brain MRI data. Researchers will explore these relationships after grouping participants according to their cerebrospinal fluid (CSF) biomarkers profile. Researchers will explain further relationships through brain Positron Tomography Emission with fluorodeoxyglucose (PET-FDG) data performed during clinical diagnostic work-up and with Apolipoprotein E (APOE) gene profile. * prospectively identifying EEG-markers predictive of clinical conversion to full-blown AD dementia and defining an algorithm for risk stratification by combining them with brain MRI, brain FDG-PET and genetic data; * assessing the longitudinal changes of electrophysiological and MRI signals throughout the AD neuropathology progression; The secondary aim of the project is to assess the accuracy of the Alzheimer-related EEG signal patterns identified in the MCI group. This will be done by comparing the EEG data with the APOE genetic information in a group of patients diagnosed with mild dementia due to Alzheimer's disease, frontotemporal dementia and Lewy-Body dementia
Interventions
DIAGNOSTIC_TESTElectroencephalogram
EEGs will be acquired to explore progressive alteration of EEG patterns throughout the neuropathology progression.
DIAGNOSTIC_TEST3 Tesla MRI
MRI evaluations will be performed to investigate structural alterations and resting state functional MRI (RS-fMRI) connectivity in participants. Longitudinal measures of cortical/subcortical atrophy and RS-fMRI connectivity will be assessed and their relationship with EEG parameters will be explored.
GENETICApolipoprotein E genetic test
At baseline, a sample of blood will be collected to perform genetic analysis (APOE alleles) for all participants
Sponsors
IRCCS San Raffaele
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Intervention study, monocentric and multiparametric
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
for all study subjects: * right-handed participants; * monolingual native Italian speakers; * age between 50-85 years old; * normal or corrected-to-normal visual acuity; * oral and written informed consent to study participation. * if assuming psychotropic drugs (i.e., benzodiazepines, antipsychotics, antidepressants), they should be at stable dosage for more than 4 weeks. Inclusion criteria for MCI patients: * diagnosis of amnestic MCI; * mini Mental State Examination (MMSE) score ≥ 24; * if assuming anticholinesterase inhibitors (i.e., galantamine, rivastigmine, donepezil) or memantine, they should be at stable dosage for more than 4 weeks; * available CSF AD biomarkers. Inclusion criteria for patients with mild dementia: * diagnosis of AD dementia, FTD or LBD. * MMSE score ≥ 15; * if assuming anticholinesterase inhibitors (i.e., galantamine, rivastigmine, donepezil) or memantine, they should be at stable dosage for more than 4 weeks.
Exclusion criteria
for patients: * secondary forms of cognitive impairment on the basis of historical data, neurologic examination, and cerebral neuroimaging findings; * very rapid cognitive decline that occurs over weeks or months, typically indicative of prion disease, neoplasm or metabolic disorders; * history of other systemic (including systemic neoplasms in the last 3 years and abnormal hepatorenal functions), neurologic (including epilepsy), psychiatric diseases, head injury, cardiovascular events, and cerebrovascular alterations; * alcohol and/or psychotropic drugs abuse; * enrolment in clinical trials testing disease-modifying drugs for AD during study; * contraindications to MRI study: 1. Cardiac pacemakers or other types of cardiac catheters; 2. metal splinters or fragments; 3. metal prostheses not compatible with the magnetic field generated during MRI; 4. claustrophobia. * Women who are pregnant or intending to become pregnant during the study; breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cortical source densities in resting-state EEG for mild cognitive impairment: Markers of differential diagnosis and dementia conversion prediction | 36 months | Source densities in resting-state high-definition EEG in patients with mild cognitive impairment, measured as cortical markers for differential diagnosis of dementias and prediction of conversion to full-blown dementia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by sensivity | 36 months | Diagnostic accuracy of EEG markers in distinguishing Alzheimer's disease (AD) from other dementias (e.g., frontotemporal dementia, Lewy-body dementia), measured as the ability to correctly identify cases that are not Alzheimer's (e.g., frontotemporal dementia, Lewy-body dementia) compared to Alzheimer's cases. |
| Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by specifity | 36 months | Diagnostic accuracy of EEG markers in distinguishing Alzheimer's disease (AD) from other dementias measured as the ability to correctly identify cases that are not Alzheimer's (e.g., frontotemporal dementia, Lewy-body dementia) compared to Alzheimer's cases |
| Relationship between Alzheimer's disease and other dementias with APOE genetic variants | 36 months | Relationship with APOE genetic variants (e.g., presence of APOE ε4 allele), quantified through cortical source densities reconstructed using sLORETA. |
Countries
Italy
Outcome results
None listed