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Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden

Published online by Cambridge University Press:  26 January 2015

Mandi Musso ,
Holly James Westervelt ,
Jeffrey D. Long ,
Erin Morgan ,
Steven Paul Woods ,
Megan M. Smith ,
Wenjing Lu ,
Jane S. Paulsen  and
the PREDICT-HD Investigators of the Huntington Study Group
Mandi Musso
Affiliation:
Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island
Holly James Westervelt
Affiliation:
Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island Department of Psychiatry, Rhode Island Hospital, Providence, Rhode Island
Jeffrey D. Long
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa
Erin Morgan
Affiliation:
Department of Psychiatry, University of California, San Diego, San Diego, California
Steven Paul Woods
Affiliation:
Department of Psychiatry, University of California, San Diego, San Diego, California
Megan M. Smith
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa
Wenjing Lu
Affiliation:
Department of Biostatistics, University of Iowa College of Public Health, Iowa City, Iowa
Jane S. Paulsen*
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa
*
Correspondence and reprint requests to: Jane S. Paulsen, 1-305 MEB, Carver College of Medicine, University of Iowa, Iowa City, IA 52242. E-mail: [email protected].
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Abstract

The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (FICV(3,877)=11.25; p<.0001; FPacedTiming(3,877)=22.89; p<.0001). When prodromal HD participants closest to HD diagnosis were compared to controls, Cohen’s d effect sizes were larger in magnitude for the within-task variability measure, paced timing (−1.01), and the SDMT (−0.79) and paced tapping coefficient of variation (CV) (−0.79) compared to the measures of across-task variability [CV (0.55); intra-individual standard deviation (0.26)]. Across-task variability may be a sensitive marker of cognitive decline in individuals with prodromal HD approaching disease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample. (JINS, 2015, 21, 8–21)

Keywords

Huntington diseaseNeuropsychological testsExecutive functionAttentionAdultCognition disorders/diagnosisCognition disorders/geneticsProdromal symptomsIntra-individual variability
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 21 , Issue 1 , January 2015 , pp. 8 - 21
Copyright
Copyright © The International Neuropsychological Society 2015 

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