The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions.
BACKGROUND
Recent advances in understanding molecular and synaptic mechanisms of intellectual disabilities (ID) in fragile X syndrome (FXS) and Down syndrome (DS) through animal models have led to targeted controlled trials with pharmacological agents designed to normalize these underlying mechanisms and improve clinical outcomes. However, several human clinical trials have failed to demonstrate efficacy of these targeted treatments to improve surrogate behavioral endpoints. Because the ultimate index of disease modification in these disorders is amelioration of ID, the validation of cognitive measures for tracking treatment response is essential. Here, we present preliminary research to validate the National Institutes of Health Toolbox Cognitive Battery (NIH-TCB) for ID.


METHODS
We completed three pilot studies of patients with FXS (total n = 63; mean age 19.3 ± 8.3 years, mean mental age 5.3 ± 1.6 years), DS (n = 47; mean age 16.1 ± 6.2, mean mental age 5.4 ± 2.0), and idiopathic ID (IID; n = 16; mean age 16.1 ± 5.0, mean mental age 6.6 ± 2.3) measuring processing speed, executive function, episodic memory, word/letter reading, receptive vocabulary, and working memory using the web-based NIH-TB-CB, addressing feasibility, test-retest reliability, construct validity, ecological validity, and syndrome differences and profiles.


RESULTS
Feasibility was good to excellent (≥80 % of participants with valid scores) for above mental age 4 years for all tests except list sorting (working memory). Test-retest stability was good to excellent, and convergent validity was similar to or better than results obtained from typically developing children in the normal sample for executive function and language measures. Examination of ecological validity revealed moderate to very strong correlations between the NIH-TCB composite and adaptive behavior and full-scale IQ measures. Syndrome/group comparisons demonstrated significant deficits for the FXS and DS groups relative to IID on attention and inhibitory control, a significant reading weakness for FXS, and a receptive vocabulary weakness for DS.


CONCLUSIONS
The NIH-TCB has potential for assessing important dimensions of cognition in persons with ID, and several tests may be useful for tracking response to intervention. However, more extensive psychometric studies, evaluation of the NIH-TCB's sensitivity to change, both developmentally and in the context of treatment, and perhaps establishing links to brain function in these populations, are required to determine the true utility of the battery as a set of outcome measures.
Translational Psychophysiology and Assessment Laboratory (T-PAL), MIND Institute, UC Davis Medical Center, Sacramento, CA USA ; Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA USA.
David
0000-0002-3460-9805
D
Hessl
Translational Psychophysiology and Assessment Laboratory (T-PAL), MIND Institute, UC Davis Medical Center, Sacramento, CA USA ; Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA USA.
Stephanie M
SM
Sansone
Department of Pediatrics, Rush University Medical Center, Chicago, IL USA ; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL USA ; Department of Biochemistry, Rush University Medical Center, Chicago, IL USA.
Elizabeth
E
Berry-Kravis
Morgridge College of Education, The University of Denver, Denver, CO USA.
Karen
K
Riley
Graduate School of Education, University of California Riverside, Riverside, CA USA.
Keith F
KF
Widaman
Translational Psychophysiology and Assessment Laboratory (T-PAL), MIND Institute, UC Davis Medical Center, Sacramento, CA USA ; Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA USA.
Leonard
L
Abbeduto
Translational Psychophysiology and Assessment Laboratory (T-PAL), MIND Institute, UC Davis Medical Center, Sacramento, CA USA ; Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA USA.
Andrea
A
Schneider
Morgridge College of Education, The University of Denver, Denver, CO USA.
Jeanine
J
Coleman
School of Medicine, Rush University Medical Center, Chicago, IL USA.
Dena
D
Oaklander
School of Medicine, Rush University Medical Center, Chicago, IL USA.
Kelly C
KC
Rhodes
Feinberg School of Medicine, Northwestern University, Chicago, IL USA.
Richard C
RC
Gershon
Assessment; Cognition; Down syndrome; FMR1 gene; Fragile X syndrome; Outcome measures