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

  • Katherine A. Gifford (a1), Jeffrey S. Phillips (a1), Lauren R. Samuels (a1) (a2), Elizabeth M. Lane (a1), Susan P. Bell (a1) (a3), Dandan Liu (a1) (a2), Timothy J. Hohman (a1), Raymond R. Romano (a1), Laura R. Fritzsche (a1), Zengqi Lu (a2), Angela L. Jefferson (a1) and for the Alzheimer’s Disease Neuroimaging Initiative...


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 (p<.01). Better regression-based slope (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal cortex in MCI. No significant associations emerged between any slope and neuroimaging variables for NC (p-values ≥.05) or AD (p-values ≥.02). Better learning performances related to larger medial temporal lobe (i.e., hippocampal volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCI only. Regression-based and late slope were most highly correlated with neuroimaging markers and explained more variance above and beyond other common memory indices, such as total learning. Simple slope may offer an acceptable alternative given its ease of calculation. (JINS, 2015, 21, 455–467)


Corresponding author

Correspondence and reprint requests to: Angela L. Jefferson, Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, 2525 West End Avenue, 12th Floor - Suite 1200, Nashville, TN 37203. E-mail:


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Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database ( As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at:



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