Cognition is 1 of 4 domains measured by the NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIH-TB), and complements modules testing motor function, sensation, and emotion. On the basis of expert panels, the cognition subdomains identified as most important for health, success in school and work, and independence in daily functioning were Executive Function, Episodic Memory, Language, Processing Speed, Working Memory, and Attention. Seven measures were designed to tap constructs within these subdomains. The instruments were validated in English, in a sample of 476 participants ranging in age from 3 to 85 years, with representation from both sexes, 3 racial/ethnic categories, and 3 levels of education. This report describes the development of the Cognition Battery and presents results on test-retest reliability, age effects on performance, and convergent and discriminant construct validity. The NIH-TB Cognition Battery is intended to serve as a brief, convenient set of measures to supplement other outcome measures in epidemiologic and longitudinal research and clinical trials. With a computerized format and national standardization, this battery will provide a "common currency" among researchers for comparisons across a wide range of studies and populations. Neurology Cognition is 1 of the 4 domains of behavioral and neurologic health assessed in the NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIH-TB). All domain measures were intended to be freely accessible, to be usable with individuals from 3 to 85 years of age, with each domain battery not to exceed 30 minutes in duration. Expert surveys were conducted and panels of research scientists and clinicians consulted in an iterative manner to rank cognitive subdomains in order of their perceived importance for health. Information was requested from experts (N 5 102) who reported sufficient familiarity with cognition to make recommendations for specific subdomains of importance. The 2 top-ranked subdomains were Executive Function (EF) (95%) and Episodic Memory (93%), followed by Language (55%), Processing Speed (52%), and Attention (50%). Many (57%) also listed a "Global Score" as important. Other cognitive subdomains were excluded because of lower priority in the rankings, coupled with the stringent time constraints on the length of the battery.The rationale for specific cognitive constructs within subdomains and instrument selection was based on a systematic review of the literature, including evidence of the known biological associations of each. The EF subdomain was deemed to include several distinct constructs, including Switching/Set Shifting, Inhibitory Control and Attention, and Working Memory. Because of
Objective-PREDICT-HD is a large-scale international study of people with the Huntington Disease CAG-repeat expansion who are not yet diagnosed with HD. The objective of this study was to determine at what stage in the HD prodrome cognitive differences from CAG-normal controls can be reliably detected.Method-For each of 738 HD CAG-expanded participants, we computed estimated years to clinical diagnosis and probability of diagnosis in five years, based on age and CAG repeat expansion number (Langbehn, Brinkman, Falush, Paulsen, & Hayden, 2004). We then stratified the sample into groups: "NEAR," estimated to be ≤ 9 years, "MID," between 9 and 15 years, and "FAR," ≥ 15 years. The control sample included 168 CAG-normal participants. Nineteen cognitive tasks were used to assess attention, working memory, psychomotor functions, episodic memory, language, recognition of facial emotion, sensory-perceptual functions, and executive functions.Results-Compared to the controls, the NEAR group showed significantly poorer performance on nearly all, and the MID group on about half of the cognitive tests (p = 0.05, Cohen's d Near as large as −1.17, Mid as large as −0.61). One test even revealed significantly poorer performance in the FAR group (Cohen's d = −0.26). Individual tasks accounted for 0.2% to 9.7% of the variance in estimated proximity to diagnosis. Overall, the cognitive battery accounted for 34% of the variance; in comparison, the UHDRS Motor Score accounted for 11.7%. Conclusions-Neurocognitive tests are robust clinical indicators of the disease process prior to reaching criteria for motor diagnosis of HD.Keywords cognitive assessment; presymptomatic; neuropsychology; psychomotor; prediagnosis Huntington disease (HD) is a progressive, fatal, autosomal dominant neurodegenerative disease that primarily affects movement, cognition, and psychiatric functions. Diagnosis of HD is based on the presence of unequivocal motor signs of HD, in conjunction with a positive genetic test for the HD CAG expansion or a confirmed family history of HD. Most people with the HD gene appear healthy throughout their youth and early adulthood, and then gradually develop signs and symptoms of HD, often leading to a diagnosis in middle age. The age of diagnosis varies in accordance with the number of CAG repeats on the expanded allele, although there is also substantial individual variability not accounted for by this genetic factor (Andrew et al., 1993;Gusella, MacDonald, Ambrose, & Duyao, 1993). A growing community of researchers is directing efforts at finding treatments to delay onset or slow the progression of early pathological changes in an attempt to reduce the tremendous personal and social costs of HD. Finding effective therapeutic or preventive treatments for HD depends critically on the ability to reliably and sensitively measure clinical signs of disease.Cognitive measures have excellent potential both for identifying individuals beginning to show subtle signs prior to the diagnosis of HD who might be suitable for clinical trials,...
This paper introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (R. C. Gershon et al., 2013) in an adult sample. This first paper in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test-retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One paper in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication.
This monograph presents the pediatric portion of the National Institutes of Health (NIH) Toolbox Cognition Battery (CB) of the NIH Toolbox for the Assessment of Neurological and Behavioral Function. The NIH Toolbox is an initiative of the Neuroscience Blueprint, a collaborative framework through which 16 NIH Institutes, Centers, and Offices jointly support neuroscience-related research, to accelerate discoveries and reduce the burden of nervous system disorders. The CB is one of four modules that measure cognitive, emotional, sensory, and motor health across the lifespan. The CB is unique in its continuity across childhood, adolescence, early adulthood, and old age, and in order to help create a common currency among disparate studies, it is also available at low cost to researchers for use in large-scale longitudinal and epidemiologic studies. This chapter describes the evolution of the CB; methods for selecting cognitive subdomains and instruments; the rationale for test design; and a validation study in children and adolescents, ages 3–15 years. Subsequent chapters feature detailed discussions of each test measure and its psychometric properties (Chapters 2–6), the factor structure of the test battery (Chapter 7), the effects of age and education on composite test scores (Chapter 8), and a final summary and discussion (Chapter 9). As the chapters in this monograph demonstrate, the CB has excellent psychometric properties, and the validation study provided evidence for the increasing differentiation of cognitive abilities with age.
Background-The PREDICT-HD study seeks to identify clinical and biological markers of Huntington's disease in premanifest individuals who have undergone predictive genetic testing.
Huntington's disease (HD) has been linked with fronto-subcortical neuropathology and behaviors consistent with this dysfunction. Little is known about these "frontal" behaviors in the earliest phase of the illness. Comparisons between participants in the Predict-HD study (745 "expansion-positive" and 163 "expansion-negative" controls) on the Frontal System Behavioral Scale looked for evidence of frontal behaviors, including apathy, disinhibition, and executive dysfunction. We were also able to compare participant and companion reporting of these frontal behaviors, as a possible indication of awareness of behaviors. Expansion-positive individuals reported significantly more of these frontal behaviors than expansion-negative peers. Self-and companion-reported frontal behaviors were related to other HD markers. Expansion-positive participants closest to HD diagnosis showed greater discrepancies with companions on ratings of frontal behaviors. Even though most are more than 10 years from HD diagnosis, mild frontal behaviors were present in this prediagnosed sample, which might make these behaviors useful as markers for HD onset. Participants/companions discrepancies, especially closest to HD diagnosis, might suggest early lack of awareness in these individuals.
The List Sorting Working Memory Test was designed to assess working memory (WM) as part of the NIH Toolbox Cognition Battery. List Sorting is a sequencing task requiring children and adults to sort and sequence stimuli that are presented visually and auditorily. Validation data are presented for 268 participants ages 20 to 85 years. A subset of participants (N=89) was retested 7 to 21 days later. As expected, the List Sorting Test had moderately high correlations with other measures of working memory and executive functioning (convergent validity) but a low correlation with a test of receptive vocabulary (discriminant validity). Furthermore, List Sorting demonstrates expected changes over the age span and has excellent test-retest reliability. Collectively, these results provide initial support the construct validity of the List Sorting Working Memory Measure as a measure of working memory. However, the relation between the List Sorting Test and general executive function has yet to be determined.
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