Using a digital assessment of multi‐day learning curves to detect preclinical AD

Abstract

AbstractBackgroundUnsupervised remote digital cognitive assessment makes frequent testing feasible and allows for measurement of learning across days on participants’ own devices. More rapid detection of diminished learning may provide a potentially valuable metric for clinical trials seeking to capture change over shorter intervals. Here, we assess whether clinically normal (CN) participants differ in their learning of the same stimuli across daily exposures depending on their β‐amyloid (Aβ) burden.MethodThe Boston Remote Assessment for Neurocognitive Health (BRANCH) (Papp et al., 2021) is a web‐based assessment administered over 7 consecutive days repeating the same stimuli each day to capture multi‐day‐learning‐curves (MDLC). The composite score includes accuracy on three cross‐modal associative memory tasks: face‐name, groceries‐prices, digits‐signs. Our sample consisted of 192 CN older adults enrolled in ongoing observational studies (mean age = 74.0, 63% female, 87% Caucasian, mean education = 16.6) who completed the tasks daily at home on their own digital devices. Participants had previously completed in‐clinic paper‐and‐pencil tests to compute a Preclinical Alzheimer’s Cognitive Composite (PACC‐5) as well as PET imaging with 11C‐Pittsburg Compound‐B to estimate globalAβ burden and classify participants as Aβ+ and Aβ‐. Mixed‐effects models controlling for age, sex, and education were used to observe the associations between Aβ status and BRANCH‐MDLC; and AUC analyses compared classification of amyloid using BRANCH‐MDLC vs. PACC‐5.ResultAdherence was high with 95% of participants completing all seven days of consecutive assessment. Aβ+ status (n = 26) was associated with a lower BRANCH‐MDLC across 7‐days (t = ‐4.03, p<.001) compared with Aβ‐ status (n = 148). Amyloid status was not associated with difference in Day 1 BRANCH or PACC‐5 performance. Furthermore, BRANCH‐MDLC showed a significant ability to classify individuals as Aβ+ vs. Aβ‐ (AUC = 0.71, p = <.001) compared to a single‐timepoint pencil‐and‐paper composite (PACC‐5) (AUC = 0.52, p = 0.56).ConclusionDiminished task learning across seven days was associated with greater amyloid pathology, whereas Day 1 of BRANCH or an in‐person supervised one‐time neuropsychological assessment were not associated with elevated amyloid. These findings signal the value of measuring differences in learning across days as a means towards capturing biomarker‐associated memory decrements and identifying those in the preclinical stage of AD.