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Episodic memory ERPs reflect preclinical Alzheimers disease progression

Raposo Pereira, F.; Chaumon, M.; Dubois, B.; Bakardjian, H.; Andrade, K.; Habert, M.-O.; Younsi, N.; La Corte, V.; George, N.

2026-07-17 neuroscience
10.64898/2026.07.11.737503 bioRxiv
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Structured AbstractO_ST_ABSBackgroundC_ST_ABSAlzheimers disease (AD) neuropathology emerges decades before symptoms, requiring sensitive, non-invasive markers for early diagnosis. We investigated behavioural and EEG markers of episodic memory in cognitively normal older adults at-risk for AD. MethodsForty-five INSIGHT-preAD cohort participants (15 progressors to prodromal AD, 15 stable {beta}-amyloid positive [A{beta}+] participants, 15 controls [A{beta}-]) completed an Old/New word recognition task during high-density EEG. Behavioural performance and memory-related evoked-related potentials (ERPs; P3, FN400, P600, post-retrieval monitoring) were analysed longitudinally over 5 years. ResultsProgressors showed significantly reduced accuracy, sensitivity, and slower responses. They showed attenuated FN400, P600, and monitoring amplitudes over left parieto-occipital regions. Source analysis revealed hypoactivation in the left inferior frontal and right posterior cingulate cortex, across components with additional disruption during P600. Stable A{beta}+ individuals showed milder P600 hypoactivations. DiscussionBehavioural and ERP alterations preceded clinical decline, supporting EEG-based markers of episodic memory decline for preclinical AD risk stratification.

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