Clinical trial NCT06826157: The Role of Advanced Electroencephalographic Data as Marker of Pathology and Prognosis in Primary Dementias
Official title: Assessing the Role of Advanced Electroencephalographic Data as Marker of Pathology and Prognosis in Primary Dementias
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
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
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2025-02-13
Enrollment: 175
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Intervention study, monocentric and multiparametric
Primary purpose: DIAGNOSTIC

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

Eligibility criteria: 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.

Primary outcomes:
measure: Cortical source densities in resting-state EEG for mild cognitive impairment: Markers of differential diagnosis and dementia conversion prediction
timeFrame: 36 months
Secondary outcomes:
measure: Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by sensivity
timeFrame: 36 months
measure: Accuracy of EEG markers in distinguishing Alzheimer's disease from other dementias measured by specifity
timeFrame: 36 months
measure: Relationship between Alzheimer's disease and other dementias with APOE genetic variants
timeFrame: 36 months
Other outcomes:
Locations:
city: Milano
country: Italy
facility: IRCCSS San Raffaele
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Massimo MF Filippi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pascual-Marqui RD. Discrete, 3D distributed, linear imaging methods of electric neuronal activity. Part 1: exact, zero error localization. 2007.
citation: 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.
citation: International AsD. World Alzheimer Report 2019: Attitudes to dementia. London: Alzheimer's Disease International, 2019
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.