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J Int Neuropsychol Soc. 2015 Jan;21(1):8-21. doi: 10.1017/S1355617714001076.

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

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1Department of Psychiatry and Human Behavior,Warren Alpert Medical School of Brown University,Providence,Rhode Island.
3Department of Psychiatry,University of Iowa Carver College of Medicine,Iowa City,Iowa.
5Department of Psychiatry,University of California,San Diego,San Diego,California.
4Department of Biostatistics,University of Iowa College of Public Health,Iowa City,Iowa.


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.


Adult; Attention; Cognition disorders/diagnosis; Cognition disorders/genetics; Executive function; Huntington disease; Intra-individual variability; Neuropsychological tests; Prodromal symptoms

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