Preliminary evaluation of the digital maze test in relation to neuropsychological tests and AD biomarkers

Abstract

AbstractBackgroundDigital cognitive tools may provide unique opportunities to detect subtle changes in preclinical Alzheimer’s disease (AD). Here, a maze test using a digital pen was evaluated in relation to AD pathological changes measured by amyloid‐β and tau burden.Method172 participants (CN = 161, MCI = 6, dementia = 5) completed the digital maze test, which included multiple “no‐choice” (NC; i.e., no decisions required to complete maze) or “choice” (CH) conditions (i.e., problem‐solving required to complete maze). Maze composite scores were calculated using the total test duration, total number of strokes, and total pen‐off‐page time for the NC and CH conditions separately. Global amyloid‐β PET was quantified with [11C]Pittsburgh‐Compound‐B (PiB) in available participants (n = 171). Entorhinal and inferior temporal tau were quantified with [18F]Flortaucipir (FTP) in available participants (n = 135). Participants completed a battery of traditional neuropsychological tests, with domain factor scores calculated for Executive Functioning (EF), Processing Speed (PS), and Memory (Mem). The associations between maze composite scores, global amyloid‐β, entorhinal tau, and inferior temporal tau were evaluated in separate linear regression models for both the total sample and CN only, correcting for age and education.ResultIn the total sample, CH‐ and NC‐composites were moderately correlated with PS and EF factor scores (r’s = .41‐.46) and less so with Mem factor scores (r’s = 0.2‐0.35). In the total sample, higher PiB was significantly associated with worse performance in NC‐composite (β = 0.543, SE = 0.249, p <.05), but not for CH‐composite (β = 0.467, SE = 0.259, p = .07). Similar results were observed in the CN only sample (NC‐composite: β = 0.468, SE = 0.237, p <.05; CH‐composite: β = 0.469, SE = 0.278, p = .09). PiB was not associated with EF or PS factor scores in the total sample or CN only. Entorhinal and inferior temporal tau were not significantly associated with any maze composites.ConclusionIn a largely cognitively normal sample, performance on the digital maze test was associated with global amyloid‐β burden, particularly in the no‐choice condition, but not with tau. Digitally captured, nuanced performance in EF and PS may be related to early amyloid‐β pathology, but less so with downstream effects of tau.