AbstractBackgroundAlzheimer’s Disease (AD) is difficult to diagnose and stage, often relying on burdensome clinical tests for neural protein aggregation and cognitive performance. Delays and errors in the accurate diagnosis of AD reduce patient outcomes and prevent early therapeutic intervention. The CASBA electroencephalography (EEG) system leverages a custom sequence of dynamic visual stimuli to elicit and translate novel and noninvasive neural signals biomarkers into accurate estimates of amyloid burden, cognitive performance, and clinical diagnosis, to facilitate clinical decision‐making in patients with cognitive decline.MethodIn a board‐approved study, human patients with mild cognitive impairment (MCI; 71.2 ± 8.2 years old), subjective cognitive decline (SCD; 70.7 ± 6.3 years old), and AD diagnosis (71.2 ± 6.6 years old), alongside amyloid PET (Anti‐Serum Amyloid P Antibody), cognitive testing (i.e. FCSRT), and clinical dementia rating (CDR). Neural signals were collected on a 64‐channel equidistant EEG system (2048Hz, Ag/AgCl; ANT Neuro, Enschede)]. Automated preprocessing and machine learning classification pipelines were developed to extract EEG features and calculate estimates of physiological and cognitive AD metrics from these EEG biomarkers.ResultCASBA accurately classified normal vs. subnormal FCSRT free recall score (threshold of 18, 77.3% balanced accuracy, 84.0% specificity, 70.6% sensitivity), SCD v. MCI/AD clinical diagnosis (79.4% balanced accuracy, 77.3% specificity, 81.5% sensitivity), CDR (threshold of 1, 79.2% balanced accuracy, 76.9% specificity, 81.5% sensitivity), and amyloid‐PET (composite threshold of 1.25, 83.0% balanced accuracy, 75.0% specificity, 91.9% sensitivity).ConclusionThe CASBA neurological assessment accurately predicts important clinical data including patient diagnosis and staging, amyloid burden, and performance on key evaluations of cognition in AD. CASBA supports physician decision making and patient stratification and suggests a new method for noninvasive tracking and repeat assessment during clinical trials. As such, the CASBA neurological assessment offers a promising new tool to advance clinical care and innovation for patients with neurodegenerative disease.