title: Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden.
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 (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.
authors: 1Department of Psychiatry and Human Behavior,Warren Alpert Medical School of Brown University,Providence,Rhode Island.
authors: Mandi
authors: M
authors: Musso
authors: 1Department of Psychiatry and Human Behavior,Warren Alpert Medical School of Brown University,Providence,Rhode Island.
authors: Holly James
authors: HJ
authors: Westervelt
authors: 3Department of Psychiatry,University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors: Jeffrey D
authors: JD
authors: Long
authors: 5Department of Psychiatry,University of California,San Diego,San Diego,California.
authors: Erin
authors: E
authors: Morgan
authors: 5Department of Psychiatry,University of California,San Diego,San Diego,California.
authors: Steven Paul
authors: SP
authors: Woods
authors: 3Department of Psychiatry,University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors: Megan M
authors: MM
authors: Smith
authors: 4Department of Biostatistics,University of Iowa College of Public Health,Iowa City,Iowa.
authors: Wenjing
authors: W
authors: Lu
authors: 3Department of Psychiatry,University of Iowa Carver College of Medicine,Iowa City,Iowa.
authors: Jane S
authors: JS
authors: Paulsen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002755:Choice Behavior; D003072:Cognition Disorders / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000503:physiopathology*; D007206:Individuality; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D062706:Prodromal Symptoms; D011930:Reaction Time; D012649:Self Concept; D013998:Time Perception / Q000502:physiology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
keywords: Adult; Attention; Cognition disorders/diagnosis; Cognition disorders/genetics; Executive function; Huntington disease; Intra-individual variability; Neuropsychological tests; Prodromal symptoms