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

NCT06826157 | Enrolling By Invitation DMC

• 1 other identifier: DEMEEG
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

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. 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. 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. 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.

Conditions

Alzheimer Disease; Lewy Body Dementia (LBD); Mild Alzheimer Disease; Frontotemporal Dementia (FTD); Mild Cognitive Impairment (MCI); Healthy Subjects

Keywords

high-definition electroencephalogram; Brain Magnetic Resonance Imaging; Biomarker profile; Positron Emission Tomography; Apolipoprotein E; Mild Cognitive Impairment; Frontotemporal dementia; Lewy-body dementia; Dementia

Outcome Measures

Primary Outcomes (1)

• Cortical source densities in resting-state EEG for mild cognitive impairment: Markers of differential diagnosis and dementia conversion prediction

  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 Outcomes (3)

• Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by sensivity

  36 months

• Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by specifity

  36 months

• Relationship between Alzheimer's disease and other dementias with APOE genetic variants

  36 months

Study Arms (1)

Clinical, EEG, brain MRI and genetic evaluations

EXPERIMENTAL

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; Diagnostic Test: 3 Tesla MRI; Genetic: Apolipoprotein E genetic test

Interventions

Electroencephalogram DIAGNOSTIC_TEST

EEGs will be acquired to explore progressive alteration of EEG patterns throughout the neuropathology progression.

Clinical, EEG, brain MRI and genetic evaluations

3 Tesla MRI DIAGNOSTIC_TEST

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.

Clinical, EEG, brain MRI and genetic evaluations

Apolipoprotein E genetic test GENETIC

At baseline, a sample of blood will be collected to perform genetic analysis (APOE alleles) for all participants

Clinical, EEG, brain MRI and genetic evaluations

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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:
• Cardiac pacemakers or other types of cardiac catheters;
• metal splinters or fragments;
• metal prostheses not compatible with the magnetic field generated during MRI;
• claustrophobia.
• Women who are pregnant or intending to become pregnant during the study; breastfeeding women.
• 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.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCSS San Raffaele

Milan, Italy, 20132, Italy

Location

Related Publications (9)

• Pascual-Marqui RD. Discrete, 3D distributed, linear imaging methods of electric neuronal activity. Part 1: exact, zero error localization. 2007.

  BACKGROUND

• Teipel SJ, Kurth J, Krause B, Grothe MJ; Alzheimer's Disease Neuroimaging Initiative. The relative importance of imaging markers for the prediction of Alzheimer's disease dementia in mild cognitive impairment - Beyond classical regression. Neuroimage Clin. 2015 May 21;8:583-93. doi: 10.1016/j.nicl.2015.05.006. eCollection 2015.

  PMID: 26199870 BACKGROUND

• International AsD. World Alzheimer Report 2019: Attitudes to dementia. London: Alzheimer's Disease International, 2019

  BACKGROUND

• Cecchetti G, Agosta F, Basaia S, Cividini C, Cursi M, Santangelo R, Caso F, Minicucci F, Magnani G, Filippi M. Resting-state electroencephalographic biomarkers of Alzheimer's disease. Neuroimage Clin. 2021;31:102711. doi: 10.1016/j.nicl.2021.102711. Epub 2021 May 29.

  PMID: 34098525 BACKGROUND

• McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O'Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M, Kosaka K. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017 Jul 4;89(1):88-100. doi: 10.1212/WNL.0000000000004058. Epub 2017 Jun 7.

  PMID: 28592453 BACKGROUND

• Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011 Sep;134(Pt 9):2456-77. doi: 10.1093/brain/awr179. Epub 2011 Aug 2.

  PMID: 21810890 BACKGROUND

• McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.

  PMID: 21514250 BACKGROUND

• Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.

  PMID: 21514249 BACKGROUND

• Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018.

  PMID: 29653606 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Lewy Body Disease; Frontotemporal Dementia; Cognitive Dysfunction; Dementia

Interventions

Electroencephalography

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Cognition Disorders

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Massimo MF Filippi, MD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor

Model Details: Intervention study, monocentric and multiparametric

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: February 13, 2025
• Study Start: November 5, 2021
• Primary Completion: April 15, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 17, 2025

Record last verified: 2025-02

Locations

IT (1)