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.

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.