A symptom of mild cognitive impairment (MCI) and Alzheimer’s disease(AD) is a flat learning profile. Learning slope calculation methods vary, andthe optimal method for capturing neuroanatomical changes associated with MCI andearly AD pathology is unclear. This study cross-sectionally compared fourdifferent learning slope measures from the Rey Auditory Verbal Learning Test(simple slope, regression-based slope, two-slope method, peak slope) tostructural neuroimaging markers of early AD neurodegeneration (hippocampalvolume, cortical thickness in parahippocampal gyrus, precuneus, and lateralprefrontal cortex) across the cognitive aging spectrum [normalcontrol (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 neuroimagingvariables, adjusting for age, sex, education, and APOE4 status. Among MCI,better learning performance on simple slope, regression-based slope, and lateslope (Trial 2–5) from the two-slope method related to largerparahippocampal thickness (all p-values<.01) andhippocampal volume (p<.01). Better regression-basedslope (p<.01) and late slope(p<.01) were related to larger ventrolateralprefrontal cortex in MCI. No significant associations emerged between any slopeand neuroimaging variables for NC (p-values ≥.05) orAD (p-values ≥.02). Better learning performancesrelated to larger medial temporal lobe (i.e., hippocampal volume,parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCIonly. Regression-based and late slope were most highly correlated withneuroimaging markers and explained more variance above and beyond other commonmemory indices, such as total learning. Simple slope may offer an acceptablealternative given its ease of calculation. (JINS, 2015,21, 455–467)