Associations between Verbal Learning Slope and Neuroimaging Markers across the Cognitive Aging Spectrum.


A symptom of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2-5) from the two-slope method related to larger parahippocampal thickness (all p-values<.01 and="" hippocampal="" volume="" better="" regression-based="" slope="" late="" were="" related="" to="" larger="" ventrolateral="" prefrontal="" cortex="" in="" mci.="" no="" significant="" associations="" emerged="" between="" any="" neuroimaging="" variables="" for="" nc="" or="" ad="" learning="" performances="" medial="" temporal="" lobe="" parahippocampal="" gyrus="" thickness="" mci="" only.="" most="" highly="" correlated="" with="" markers="" explained="" more="" variance="" above="" beyond="" other="" common="" memory="" indices="" such="" as="" total="" learning.="" simple="" may="" offer="" an="" acceptable="" alternative="" given="" its="" ease="" of="" calculation.="">