Rome, 29 December 2025 – Not all patients with mild cognitive disorder – Mild Cognitive Impairment (MCI) an intermediate condition between normal brain aging and dementia – develop dementia: some, despite presenting numerous biological risk factors and alterations of specifics biomarkersshow a surprising ability to resistance to disease progression.
The data that emerged does not represent absolute news and is in line with what was confirmed by a group of Italian researchers, who however developed a particularly innovative approach. The results are described in the article “Electroencephalography-based signatures of cognitive resilience in individuals with stable mild cognitive impairment despite carrying a high-risk for dementia” published in the prestigious American magazine Alzheimer’s & Dementia.
What the study says
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The study, whose first author is Chiara Pappaletterabiomedical engineer and researcher at the IRCCS San Raffaele in Rome, is part of the INTERCEPTOR project, a large research program started in 2018 and financed by the Ministry of Health and the Italian Medicines Agency (AIFA), dedicated to the early identification of the mechanisms that lead to the development of dementia.
“The research – explains the prof. Paolo Maria Rossinidirector of the Department of Neuroscience of the Roman Institute, responsible for Interceptor and the study – involved 351 subjects with mild cognitive impairmentfollowed for three years”. At the time of enrollment, the participants underwent an extremely thorough evaluation: CSF and plasma biomarkers (amyloid and tau), genetics (APOE), neuroimaging (magnetic resonance imaging and PET), electroencephalogram with brain connectivity study, as well as neuropsychological tests and comprehensive clinical evaluations.
Results after 3 years of follow-up
At the end of the follow-up, approximately a third of patients developed a form of dementia22% a form clinically attributable to Alzheimer’s disease. However, a significant proportion of subjects, over 52% of those with 2 important risk biomarkers altered (hippocampal volume measured by MRI and PET), showed no progression towards dementia at the end of 3 years of follow-up.
“It was at this point that we asked ourselves the question crucial question – continues Rossini – why do subjects with mild cognitive disorder, therefore already at risk, and with altered biomarkers such as PET and hippocampal volumetry not develop the disease?”.
To give a first answer the researchers have compared the electroencephalogram of patients who developed dementia with that of subjects who remained clinically stable, defined “stable resilient”. The analysis of brain connectivity (a very advanced method of analyzing the electroencephalographic signal) has highlighted distinctive EEG patterns in resilient subjects.
“We have seen increased capacity synchronization and connection of the frontal lobes to specific brain rhythmsas if these areas were strongly interconnected with each other”, explains Rossini. “Moreover – he continues – we found significant differences in the relationship between alpha rhythm and delta rhythm, in particular at the level of right temporal lobe. The alpha rhythm is typical of the alert and relaxed brain, while the delta is more representative of the deep sleep phases.”
Brain resilience: when the brain compensates for damage
According to the researchers, these neurophysiological characteristics represent real signs of brain resiliencemechanisms that allow the brain to compensate for the potential damage associated with biological risk factors, maintaining cognitive functions for longer.
“The study of resilience factors represents a new and strategic approach”, concludes Rossini, “it is not just about reducing risk, but about identify and strengthen what makes the brain capable of resistance. In the future, these mechanisms could become a therapeutic target, with the aim of strengthening brain resilience and preserving people’s autonomy for as long as possible.”
New perspectives for prevention and therapies
The research thus proposes a new vision of neurodegenerative diseasesno longer considered exclusively as the inevitable outcome of the accumulation of risk factors, but as the result of a dynamic balance between risk and resilience. A perspective that paves the way for new diagnostic toolsto more targeted prevention strategies and increasingly personalized treatment paths.
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