Electroencephalography-based signatures of cognitive resilience in individuals with stable mild cognitive impairment despite carrying a high-risk for progression to dementia.

INTRODUCTION: Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia, with 30%-50% of cases progressing to dementia. However, some individuals remain stable over time, even when presenting biomarker profiles that indicate high risk. Understanding the neural mechanisms underlying this resilience is essential for developing targeted preventive strategies. METHODS: Within the Italian INTERCEPTOR project, we investigated electroencephalography (EEG) markers of resilience in MCI individuals who exhibited reduced hippocampal volume and abnormal fluorodeoxyglucose-positron emission tomography (FDG-PET) at baseline but remained stable and did not progress to dementia after 36 months. Two MCI subgroups were compared: those who do not convert (sMCI-resilient) and those who converted (cMCI) to dementia. A third group of cognitively healthy, age- and education-matched older adults served as controls. Baseline EEG analyses examined spectral power, delta/alpha ratio, functional connectivity, and graph-theoretical network properties. RESULTS: Compared with sMCI-resilient subjects, cMCI individuals exhibited increased frontal delta power, reduced posterior alpha power, and an elevated delta/alpha ratio in the right temporal region, consistent with cortical dysfunction. In contrast, sMCI-resilient subjects showed stronger frontal and temporal alpha-band connectivity and higher small-world (SW) index values in the alpha-2 band, suggesting more efficient network organization. DISCUSSION: Specific EEG signatures-characterized by adaptive spectral patterns, preserved connectivity, and efficient network topology-may represent neurophysiological correlates of resilience in high-risk MCI. These findings highlight the potential of EEG markers for early intervention and stratification strategies in individuals at risk of dementia. Highlights: Electroencephalography (EEG) markers differentiate resilience and progression in mild cognitive impairment (MCI) individuals with high-risk biomarker profiles.Converters (cMCI) show increased delta power, reduced alpha activity, and higher delta/alpha ratios, indicating cortical dysfunction.Resilient MCI (sMCI) maintain healthy delta profiles, enhanced frontal alpha power, and stronger anterior connectivity.Graph-theoretical analysis reveals higher small-world (SW) index in resilient MCI, suggesting efficient and flexible network organization.EEG is a non-invasive, accessible tool to capture both risk and resilience factors, with potential for early diagnosis and personalized interventions.