The NIH Toolbox for cognitive surveillance in Duchenne muscular dystrophy

Abstract

Objective We performed a prospective, cross‐sectional cognitive assessment in subjects with Duchenne Muscular Dystrophy (DMD) and their biological mothers. Methods Thirty subjects with out‐of‐frame mutations in the dystrophin (DMD) gene, and 25 biological mothers were evaluated using the National Institutes of Health Toolbox Cognition Battery (NIHTB‐CB). A parent completed the Behavior Rating Inventory of Executive Functioning (BRIEF), a standardized rating scale of executive functioning, for their child. Mothers completed self‐reports of BRIEF and Neuro Quality‐of‐Life (NeuroQoL) Cognitive Function. Results Overall, the subjects with DMD scored approximately one standard deviation (SD) below age‐corrected norms on the NIHTB‐CB Total Cognition score. They scored 1.5 SD below age‐corrected norms in Fluid Cognition, which evaluates the cognitive domains of executive function, working memory, episodic memory, attention, and processing speed. Their performance was consistent with age expectations (i.e., within 1 SD below age‐corrected norms) in Crystalized Cognition, which evaluates vocabulary and reading. Subjects with DMD had higher T‐scores in several domains of BRIEF, demonstrating greater difficulty in executive functioning. The biological mothers had overall average or above average T‐scores on NIHTB‐CB. Mothers who were carriers of DMD mutation performed lower overall compared to mothers who were not carriers of DMD mutation (Cohen’s d = −1.1). Carrier mothers performed lower than average (1.5 SD) in Executive Function, measured by Flanker Inhibitory Control and Attention. Biological mothers scored within expected score ranges for adults in BRIEF and NeuroQoL. Interpretation The NIHTB‐CB, combined with standardized self‐reported measures, can be a sensitive screening tool for cognitive surveillance in DMD.

Cognition of the mothers of patients with Duchenne muscular dystrophy

“…C‐Ms scored lower than average on executive function, as measured using the Flanker Inhibitory Control and Attention Test. On population‐normed data, the C‐Ms had lower scores on the task of attention and working memory compared with NC‐Ms 17 . Similarly, we found that C‐Ms performed worse on the attention, working memory, and executive function components.…”

“…No differences were found between C-Ms and NC-Ms on any of the other tests. working memory compared with NC-Ms. 17 Similarly, we found that C-Ms performed worse on the attention, working memory, and executive function components. However, we found these findings between the C-Ms and the control group.…”

Longitudinal Evaluation of Working Memory in Duchenne Muscular Dystrophy

“…Some of the neuropsychological measures used in earlier studies do not offer a continuity of measurement. In a lead study, we show that the NIH Toolbox-a scientifically robust neurobehavioral health measure-is a valid analytic tool for cognitive surveillance in DMD [68]. Last, well-powered natural history studies of cognition through a team-science approach will be extremely beneficial in DMD.…”

249th ENMC International Workshop: The role of brain dystrophin in muscular dystrophy: Implications for clinical care and translational research, Hoofddorp, The Netherlands, November 29th–December 1st 2019

“…Yet the lack of reliable and robust clinical outcome measures and a well-designed natural history evaluating cognition are major impediments to progress. The use of technology-enabled tools like the NIH Toolbox ( https://www.healthmeasures.net/ explore-measurement-systems/nih-toolbox) [42] can allow for an increase in cognitive surveillance in DMD, and measures within the NIH Toolbox also has promise as a performance outcome measure for clinical trials.…”