Performance and validation of a digital memory test across the Alzheimer's disease continuum.
Toniolo S., Attaallah B., Maio MR., Tabi YA., Slavkova E., Klar VS., Saleh Y., Idris MI., Turner V., Preul C., Srowig A., Butler C., Thompson S., Manohar SG., Finke K., Husain M.
Digital cognitive testing using online platforms has emerged as a potentially transformative tool in clinical neuroscience. In theory, it could provide a powerful means of screening for and tracking cognitive performance in people at risk of developing conditions such as Alzheimer's disease. Here we investigate whether digital metrics derived from an in-person administered, tablet-based short-term memory task-the 'What was where?' Oxford Memory Task-were able to clinically stratify patients at different points within the Alzheimer's disease continuum and to track disease progression over time. Performance of these metrics compared to traditional neuropsychological pen-and-paper screening tests of cognition was also analysed. A total of 325 people participated in this study: 49 patients with subjective cognitive decline, 57 with mild cognitive impairment, 63 with Alzheimer's disease dementia and 156 elderly healthy controls. Most digital metrics were able to discriminate between healthy controls and patients with mild cognitive impairment and between mild cognitive impairment and Alzheimer's disease patients. Some, including Absolute Localization Error, also differed significantly between patients with subjective cognitive decline and mild cognitive impairment. Identification accuracy was the best predictor of hippocampal atrophy, performing as well as standard screening neuropsychological tests. A linear support vector model combining digital metrics achieved high accuracy and performed at par with standard testing in discriminating between elderly healthy controls and subjective cognitive decline (area under the curve 0.82) and between subjective cognitive decline and mild cognitive impairment (area under the curve 0.92), while performing worse in classifying between mild cognitive impairment and Alzheimer's disease patients (area under the curve 0.75). Memory imprecision was able to predict cognitive decline on standard cognitive tests over one year. Overall, these findings show how it might be possible to use a digital memory test in clinics and clinical trial contexts to stratify and track performance across the Alzheimer's disease continuum.