Abstract

Earlier diagnosis of Alzheimer's disease requires biomarkers sensitive to associated structural and functional changes. While considerable progress has been made in the development of structural biomarkers, functional biomarkers of early cognitive change, unconfounded by effort, practice and level of education, are still needed. We present Fastball, a new EEG method for the passive and objective measurement of recognition memory, that requires no behavioural memory response or comprehension of the task . Younger adults, older adults and Alzheimer's disease patients (n = 20 per group) completed the Fastball task, lasting just under 3 min. Participants passively viewed rapidly presented images and EEG assessed their automatic ability to differentiate between images based on previous exposure, i.e. old/new. Participants were not instructed to attend to previously seen images and provided no behavioural response. Following the Fastball task, participants completed a two-alternative forced choice (2AFC) task to measure their explicit behavioural recognition of previously seen stimuli. Fastball EEG detected significantly impaired recognition memory in Alzheimer's disease compared to healthy older adults (P < 0.001, Cohen's d = 1.52), whereas behavioural recognition was not significantly different between Alzheimer's disease and healthy older adults. Alzheimer's disease patients could be discriminated with high accuracy from healthy older adult controls using the Fastball measure of recognition memory (AUC = 0.86, P < 0.001), whereas discrimination performance was poor using behavioural 2AFC accuracy (AUC = 0.63, P = 0.148). There were no significant effects of healthy ageing, with older and younger adult controls performing equivalently in both the Fastball task and behavioural 2AFC task. Early diagnosis of Alzheimer's disease offers potential for early treatment when quality of life and independence can be retained through disease modification and cognitive enhancement. Fastball provides an alternative way of testing recognition responses that holds promise as a functional marker of disease pathology in stages where behavioural performance deficits are not yet evident. It is passive, non-invasive, quick to administer and uses cheap, scalable EEG technology. Fastball provides a new powerful method for the assessment of cognition in dementia and opens a new door in the development of early diagnosis tools.