Novel markers of cognitive impairment and resilience using digital and plasma biomarkers across different neurodegenerative diseases

Blood-based biomarkers enable early diagnosis of neurodegenerative diseases in a cost-effective and non-invasive way. Digital cognitive measures can capture early signs of cognitive impairment remotely and at scale. Their combination offers important opportunities for effective screening. We evaluated the performance of a new proteomic assay and a fully remote digital platform in a large memory clinic population (n = 391). Plasma biomarkers were measured using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) central nervous system panel. OCTAL (Oxford Cognitive Testing Portal) digital cognitive testing platform was used to measure cognition. Distinct proteomic patterns could be identified across different neurodegenerative diseases and associate with specific cognitive functions. Alzheimer's Disease (e.g., pTau217), and novel proteomics biomarkers (e.g., ACHE and IL6R) were highly correlated with worse cognition. A cluster of biomarkers, including PRDX6, was overexpressed in healthy controls and associated with better cognition, indexing cognitive resilience.