Biomarker-Informed Interpretation of Dyadic Cognitive Function Index Scores in Cognitively Unimpaired Older Adults

Introduction: Participant- and study partner-reported Cognitive Function Index scores may provide complementary information, but it remains unclear whether Alzheimer's disease biomarkers are associated with CFI scores across reporters, reporter-specific imbalance, or both. Methods: Using A4/LEARN screening data (screening sample, N = 1,686; primary dyadic analytic sample, N = 1,682; CDR global score = 0), we jointly modeled participant-reported (CFI-PT) and study partner-reported (CFI-SP) scores in long format to evaluate biomarker associations with CFI scores and biomarker x reporter interactions. As a secondary analysis, we compared tau PET with plasma p-tau217. Results: In an A4/LEARN-adapted regional extent model, reporter balance varied across amyloid regional extent categories, with the largest participant-leading contrast observed in the exploratory restricted early cortical subgroup. Tau PET was associated with higher CFI scores, but this association did not differ detectably between reporters. Plasma p-tau217 showed no clear CFI association or reporter-specific interaction in the A4-derived, amyloid-enriched subset. Discussion: Amyloid regional extent and tau PET were associated with different features of dyadic CFI data: reporter balance and CFI burden across reporters, respectively. Joint interpretation of CFI-PT and CFI-SP may support biomarker-informed interpretation of the instrument, although the cross-sectional findings require replication and longitudinal validation.