La Corte, V. | bioRxiv Science

bioRxiv2026

Episodic memory ERPs reflect preclinical Alzheimers disease progression

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.

neuroscience↗

bioRxiv2022

Why Are Alzheimer's Disease Patients Unaware of their Memory Deficits?

Anosognosia, or the lack of awareness of ones own impairment, is frequent for memory deficits in patients with Alzheimers disease (AD). Although often related to frontal dysfunctions, the neural mechanisms of anosognosia remain largely unknown. We hypothesized that anosognosia in AD may result from a failure in the error-monitoring system, thus preventing patients from being aware of and learning from their own errors. We therefore investigated the event-related potentials evoked by erroneous responses during a memory task in two groups of amyloid positive individuals who had only subjective memory complaints at study entry: 1) those who progressed to AD; and 2) those who remained cognitively normal after five years of follow-up. Our findings revealed direct evidence of a failure in the error-monitoring system at early stages of AD, suggesting that it may be the critical neural substrate of anosognosia in this neurodegenerative disorder.

neuroscience↗