The relationship between learning slopes and Alzheimer's Disease biomarkers in cognitively unimpaired participants with and without subjective memory concerns.

Objective: Learning slopes represent serial acquisition of information during list-learning tasks. Although several calculations for learning slopes exist, the Learning Ratio (LR) has recently demonstrated the highest sensitivity toward changes in cognition and Alzheimer's disease (AD) biomarkers. However, investigation of learning slopes in cognitively unimpaired individuals with subjective memory concerns (SMC) has been limited. The current study examines the association of learning slopes to SMC, and the role of SMC in the relationship between learning slopes and AD biomarkers in cognitively unimpaired individuals.

Method: Data from 950 cognitively unimpaired participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 89) were used to calculate learning slope metrics. Learning slopes among those with and without SMC were compared with demographic correction, and the relationships of learning slopes with AD biomarkers of bilateral hippocampal volume and β-amyloid pathology were determined.

Results: Learning slopes were consistently predictive of hippocampal atrophy and β-amyloid deposition. Results were heightened for LR relative to the other learning slopes. Additionally, interaction analyses revealed different associations between learning slopes and hippocampal volume as a function of SMC status.

Conclusions: Learning slopes appear to be sensitive to SMC and AD biomarkers, with SMC status influencing the relationship in cognitively unimpaired participants. These findings advance our knowledge of SMC, and suggest that LR - in particular - can be an important tool for the detection of AD pathology in both SMC and in AD clinical trials.