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

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

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:

• 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.

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.