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

  • Mandi Musso (a1), Holly James Westervelt (a1) (a2), Jeffrey D. Long (a3) (a4), Erin Morgan (a5), Steven Paul Woods (a5), Megan M. Smith (a3), Wenjing Lu (a4), Jane S. Paulsen (a3) and the PREDICT-HD Investigators of the Huntington Study Group...

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 (F ICV(3,877)=11.25; p<.0001; F PacedTiming(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)

Corresponding author
Correspondence and reprint requests to: Jane S. Paulsen, 1-305 MEB, Carver College of Medicine, University of Iowa, Iowa City, IA 52242. E-mail:
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