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Estimation of positron-emission-tomography amyloid load and related biomarkers in Alzheimer's disease using evoked potential tomography electroencephalography

Rauchmann, B.-S.; Hamet, J.; Lai, J.; Kafi, H.; Rexwinkle, J. T.; Brendel, M.; Franzmeier, N.; Kurz, C.; Pogarell, O.; Levin, J.; Hoglinger, G.; Perneczky, R.

2025-07-10 neurology
10.1101/2025.07.08.25331158 medRxiv
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INTRODUCTIONDementia affects over 50 million individuals globally, predominantly due to Alzheimers disease (AD). Effective early detection, monitoring, and intervention remain clinical challenges, and existing diagnostic frameworks lack unified portable solutions for assessing multiple biomarkers. METHODSThis study evaluates Evoked Potential Tomography (EPT), an EEG-based technique using a novel visual evoked potential protocol. We developed an automated pipeline including EEG preprocessing, event-related potential feature extraction, feature selection, optimization, and regression modeling to estimate key AD biomarkers: PET-amyloid standardized uptake value ratio (SUVR), CSF phosphorylated tau 181 (p-tau181), Free and Cued Selective Reminding Test (FCSRT) scores, and Mini-Mental State Examination (MMSE) scores. RESULTSRegression modeling of ERP features from early-AD participants yielded strong Spearmans correlations between predicted and true values for PET-amyloid SUVR, p-tau181, FCSRT, and MMSE scores, with r = 0.8-0.94. DISCUSSIONDespite limitations, findings support EPTs potential for sensitive, accurate, and non-invasive early AD detection and progression monitoring. Further validation is ongoing. HighlightsO_LIERP amplitudes differed by dementia diagnosis during visual stimulation. C_LIO_LIERP regression outperformed CSF amyloid ratio in PET amyloid estimation. C_LIO_LIERP features predicted p-tau and cognition (r = 0.8-0.94). C_LIO_LIEvoked Potential Tomography may track Alzheimers progression effectively. C_LI Research in ContextO_LISystematic Review: The authors conducted a systematic literature review using traditional databases (e.g., PubMed). Although Alzheimers disease (AD) biomarkers are extensively studied, no single portable technology currently assesses all essential biomarkers simultaneously. Relevant references are appropriately cited. C_LIO_LIInterpretation: Our results demonstrate that integrating the Evoked Potential Tomography (EPT) protocol with an automated EEG processing and biomarker estimation pipeline effectively estimates multiple critical AD biomarkers that are useful in tracking disease progression using a single 30-minute EEG session. C_LIO_LIFuture Directions: The study highlights the promise of EPT as a non-invasive tool for AD screening and diagnostics. Further validation of this method could significantly advance clinical management and research, facilitating earlier AD detection, precise cohort selection, and targeted therapeutic interventions. C_LI

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