Comparing longitudinal trajectories of Storyteller and CDR-SB: Initial data from ADNI4

Fristed E, Weston J, for the Alzheimer’s Disease Neuroimaging Initiative*

Background: Accurate measures of cognitive change are critical for detecting treatment effects in clinical trials for Alzheimer’s disease. Storyteller, a self-administered remote story-recall task, enables low-burden repeat assessments in ADNI4. We compared its longitudinal trajectories to the Clinical Dementia Rating sum-of-boxes (CDR-SB) between Mild Cognitive Impairment (MCI) and Cognitively Unimpaired (CU) participants.

Methods: 416 ADNI4 participants with baseline clinical diagnosis of MCI (n=120) or CU (n=296) who completed both Storyteller and the Clinical Dementia Rating (CDR) at baseline were included. At analysis, 136 (103 CU; 33 MCI) had completed Storyteller and 58 (50 CU; 8 MCI) had completed CDR at one-year follow-up, and 246 (184 CU; 62 MCI) and 52 (36 CU; 16 MCI) had completed Storyteller at six-month and eighteen-month follow-up, respectively. Separate mixed models for repeated measures examined fixed effects of time, diagnosis, time*diagnosis interaction, age, sex, and education, with random intercepts by participant. Primary outcome was the time*diagnosis interaction.

Results: Groups were balanced for age (p=0.073) and years of education (p=0.420), but different in female proportion (CU 65.9%; MCI 42.5%; p<0.001). For Storyteller and CDR-SB, groups differed by baseline score (Storyteller: HC 63.7±12.1, MCI 54.2±12.5, p<0.001; CDR-SB: HC 0.06±0.19, MCI 1.40±0.98, p<0.001). In the mixed models, Storyteller showed significant time*diagnosis interaction (β=-0.453±0.109, p<0.001), with HC improving (+0.541 points/month) and MCI stable (+0.088 points/month); while CDR-SB showed no significant interaction (β=-0.023±0.018, p=0.203).

Conclusion: Unlike the CDR-SB, Storyteller showed significant differences in cognitive trajectories between CU and MCI. The findings are limited by the small sample sizes at follow-up. A larger sample is being collected in ADNI4, where the results will be validated.

Keywords: endpoint, digital cognitive assessment, speech, artificial intelligence

Clinical Trial Registry: NCT05617014; https://clinicaltrials.gov

Data Deposition: https://adni.loni.usc.edu/

Disclosures: EF and JW are directors and shareholders of and consultants to Novoic Ltd.