The Role of Advanced Electroencephalographic Data As Marker of Pathology and Prognosis in Primary Dementias

February 13, 2025 updated by: Prof. Massimo Filippi, IRCCS San Raffaele

Assessing the Role of Advanced Electroencephalographic Data As Marker of Pathology and Prognosis in Primary Dementias

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

175

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy, 20132
        • IRCCSS San Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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.

Exclusion criteria for healthy controls

  • 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;
  • contraindications to MRI study (see above);
  • women who are pregnant or intending to become pregnant during the study; breastfeeding women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clinical, EEG, brain MRI and genetic evaluations
Participants will be screened to evaluate their eligibility. They will undergo clinical and cognitive assessments in addition to 32-channel EEG and 3 Tesla MRI at baseline (T0) and every year for 3 years. Furthermore, at baseline, a known genetic risk factors for AD will be explored (e., APOE gene profile).
Diagnostic test: Electroencephalogram
EEGs will be acquired to explore progressive alteration of EEG patterns throughout the neuropathology progression.
Diagnostic test: 3 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.
Genetic: Apolipoprotein E genetic test
At baseline, a sample of blood will be collected to perform genetic analysis (APOE alleles) for all participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortical source densities in resting-state EEG for mild cognitive impairment: Markers of differential diagnosis and dementia conversion prediction
Time Frame: 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
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between Alzheimer's disease and other dementias with APOE genetic variants
Time Frame: 36 months
Relationship with APOE genetic variants (e.g., presence of APOE ε4 allele), quantified through cortical source densities reconstructed using sLORETA.
36 months
Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by sensivity
Time Frame: 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.
36 months
Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by specifity
Time Frame: 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
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Investigators

  • Principal Investigator: Massimo MF Filippi, MD, IRCCS Ospedale San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 5, 2021

Primary Completion (Estimated)

April 15, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

December 4, 2024

First Submitted That Met QC Criteria

February 10, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 13, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DEMEEG

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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