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Associations between Verbal Learning Slope and Neuroimaging Markersacross the Cognitive Aging Spectrum

Published online by Cambridge University Press:  29 July 2015

Katherine A. Gifford
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
Jeffrey S. Phillips
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
Lauren R. Samuels
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
Elizabeth M. Lane
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
Susan P. Bell
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Dandan Liu
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
Timothy J. Hohman
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
Raymond R. Romano III
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
Laura R. Fritzsche
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
Zengqi Lu
Affiliation:
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
Angela L. Jefferson*
Affiliation:
Vanderbilt Memory & Alzheimer’s Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee
*
Correspondence and reprint requests to: Angela L. Jefferson,Vanderbilt Memory & Alzheimer’s Center, Department ofNeurology, Vanderbilt University Medical Center, 2525 West End Avenue, 12thFloor - Suite 1200, Nashville, TN 37203. E-mail: angela.jefferson@vanderbilt.edu

Abstract

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)

Type
Research Articles
Copyright
Copyright © The International Neuropsychological Society 2015 

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Footnotes

*

Data used in preparation of this article were obtained from theAlzheimer’s Disease Neuroimaging Initiative (ADNI) database(adni.loni.usc.edu). As such, the investigators within the ADNIcontributed to the design and implementation of ADNI and/orprovided data but did not participate in analysis or writing of thisreport. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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