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

ABSTRACT

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.

KEYWORDS:

• Learning slopes
• memory
• subjective memory concerns
• hippocampal volumes
• β-amyloid

Disclosure statement

No potential conflict of interest was reported by the authors.

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All authors have read and provided consent to be associated with this manuscript.

Additional information

Funding

Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) [National Institutes of Health Grant U01 AG024904] and DOD ADNI [Department of Defense award number W81XWH-12-2-0012]. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.