Predicting clinical decline over 36 months with a memory‐based digital biomarker

Abstract

AbstractBackgroundWord‐list recall tests are routinely employed in clinical practice for dementia screening. Process scoring and latent modeling of these tests, where underlying neurocognitive mechanisms are exploited, have shown potential to enhance test accuracy without requiring test redesign. We examined Embic’s digital biomarker M, a measure of recall derived from multinomial processing trees and hierarchical Bayesian computational methods, as a predictor of conversion to mild cognitive impairment (MCI) and Alzheimer’s disease (AD), and of increase in Clinical Dementia Rating (CDR) score.MethodsSecondary data analyses were carried out from ADNI data. M was computed from Rey’s AVLT data, and compared to standard AVLT clinical metrics (total and delayed recall). We conducted logistic regression analyses with diagnosis at 36 months (normal vs. MCI + AD) as outcome; all 169 participants were classified as normal at baseline, and 13 of these progressed to a clinical diagnosis (see Table 1). We controlled for baseline age, gender and years of education; and ran separate analyses with other metrics to avoid multicollinearity. We then repeated the same analytical framework with CDR scores (stable at 0 vs. increased to 0.5 or 1) at 36 months as outcome: stable participants were 141, and 24 increased (see Table 2). Covariates and predictors were the same as in the previous analysis.Results M predicted conversion to MCI or AD after three years (FDR‐corrected p value = 0.048), while neither AVLT total nor delayed recall did. Performance metrics showed that M generated 92% accuracy, or probability of yielding a correct classification, and 100% specificity, or no false positives (Figure 1). Analogously, M, but not standard AVLT metrics, also predicted a CDR increase after three years (FDR‐corrected p value = 0.003), with high accuracy (84%), specificity (96%), and precision (80%), or positive predictive value (Figure 2). Sensitivity analyses with ordinal regression broadly confirmed these findings.ConclusionsThese results indicate Embic’s digital biomarker M outperforms some of AVLT’s traditional metrics in identifying individuals who will progress to MCI and AD after three years, from a healthy baseline.