Predicting CDR status over 36 months with a recall-based digital cognitive biomarker.

Introduction: Word-list recall tests are routinely used for cognitive assessment, and process scoring may improve their accuracy. We examined whether Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) derived, process-based digital cognitive biomarkers (DCBs) at baseline predicted Clinical Dementia Rating (CDR) longitudinally and compared them to standard metrics.

Methods: Analyses were performed with Alzheimer's Disease Neuroimaging Initiative (ADNI) data from 330 participants (mean age = 71.4 ± 7.2). We conducted regression analyses predicting CDR at 36 months, controlling for demographics and genetic risk, with ADAS-Cog traditional scores and DCBs as predictors.

Results: The best predictor of CDR at 36 months was M, a DCB reflecting recall ability (area under the curve = 0.84), outperforming traditional scores. Diagnostic results suggest that M may be particularly useful to identify individuals who are unlikely to decline.

Discussion: These results suggest that M outperforms ADAS-Cog traditional metrics and supports process scoring for word-list recall tests. More research is needed to determine further applicability with other tests and populations.

Highlights: Process scoring and latent modeling were more effective than traditional scoring. Latent recall ability (M) was the best predictor of Clinical Dementia Rating decline at 36 months. The top digital cognitive biomarker model had odds ≈ 90 times greater than the top Alzheimer's Disease Assessment Scale-Cognitive subscale model. Particularly high negative predictive value supports literature on cognitive testing as a useful screen. Consideration of both cognitive and pathological outcomes is needed.