Association of deficits in short-term learning and Aβ and hippocampal volume in cognitively normal adults.

To determine the extent to which deficits in learning over 6 days are associated with β-amyloid-positive (Aβ+) and hippocampal volume in cognitively normal (CN) adults. Eighty CN older adults who had undergone PET neuroimaging to determine Aβ status (n = 42 Aβ- and 38 Aβ+), MRI to determine hippocampal and ventricular volume, and repeated assessment of memory were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Participants completed the Online Repeatable Cognitive Assessment-Language Learning Test (ORCA-LLT), which required they learn associations between 50 Chinese characters and their English language equivalents over 6 days. ORCA-LLT assessments were supervised on the first day and were completed remotely online for all remaining days. Learning curves in the Aβ+ CN participants were significantly worse than those in matched Aβ- CN participants, with the magnitude of this difference very large ( These results suggest that in CN participants, Aβ+ is associated more strongly with a deficit in learning than any aspect of memory dysfunction. Slower rates of learning in Aβ+ CN participants were associated with hippocampal volume loss. Considered together, these data suggest that the primary cognitive consequence of Aβ+ is a failure to benefit from experience when exposed to novel stimuli, even over very short periods.

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© 2020 American Academy of Neurology.