A prospective, cross-sectional assessment suggests that patients with DMD can be adequately assessed for cognition in a brief period of time using the NIHTB‐CB, and additionally suggested a cognitive vulnerability in mothers who were carriers of DMD mutation.
Mathula Thangarajh, MD, PhD
In combination with a pair of self-reported assessments, the National Institutes of Health Toolbox Cognition Battery (NIHTB‐CB) shows potential as a sensitive screening tool for cognitive surveillance in patients with Duchenne muscular dystrophy (DMD).1
Patients scores were 1.5 standard deviations (SD) below the Fluid Cognition age-corrected norms, and they had higher T-scores in several domains of Behavior Rating Inventory of Executive Functioning (BRIEF), as completed by the parent, suggesting greater difficulty. Their performances were consistent with expectations for their respective ages in Crystalized Cognition.
“Resource constraints may lead medical teams to prioritize one service over the other, especially during lengthy multidisciplinary care visits,” wrote study author Mathula Thangarajh, MD, PhD, neurophysiologist, Children's National Health System, and colleagues. “These system‐based challenges, including fewer mental health specialists being part of multidisciplinary medical teams, or long‐wait times for formal neuropsychological evaluation, are significant barriers to adherence to standard‐of‐care guidelines.”
For patients with DMD, cognitive health is adequately evaluated in fewer than 25% of patients, the authors noted. This pilot study chose the NIHTB-CB due to 5 key factors: the availability of population‐normed data, its assessment across the life‐span, the ability to control for education for adults or maternal education for children, its portability (it is available as an iPad‐app), and its approximate 30-minute assessment duration.
The NIHTB-CB is a combination of a number of tests—Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, Flanker, Picture Sequence Memory Test, Picture Vocabulary Test, Oral Reading Recognition Test, Pattern Comparison Processing Speed Test, and the List Sorting Working Memory Test. It also has an early childhood variation for children aged 3—6 years, which includes the Dimensional Change Card Sort Test, Flanker, Picture Sequence Memory, and Picture Vocabulary.2
The NIHTB‐CB was able to capture relative deficits in executive function, working memory, and attention among patients via Dimensional Change Card Sort (mean, 52 [SD, 12]), List Sorting Working Memory, and Flanker Inhibitory Control (mean, 41 [SD, 16]).
“Our data indicate that the NIHTB‐CB identifies cognitive domains specifically affected in DMD,” Thangarajh and colleagues wrote. “Notably, while children with DMD mutations had overall average scores, the NIHTB‐CB was able to discriminate between relative strengths and weaknesses.”
Overall, biological mothers had average or above-average T scores on the NIHTB‐CB, and those who were carriers of DMD mutation performing lower compared to those without (Cohen’s d = −1.1). Twenty‐one mothers rated their own perceived cognitive functioning on the Neuro Quality‐of‐Life (NeuroQoL), with a mean score of 49 (SD, 7.5), within the expected score range for adults.
“A novel finding of our study is the observed cognitive vulnerability in carriers of DMD mutation,” Thangarajh and colleagues wrote. “In particular, women carriers of DMD performed lowest in the task of working memory and attention, compared to noncarrier mothers on population‐normed data.”
Thangarajh et al. also pointed out that none of the biological mothers self-reported any cognitive alarms, as their scores on performance-based tasks suggested normal cognitive reserve. Ultimately, though, they performed “sub‐par compared to noncarrier women drawn for this same study.” Mothers completed self‐reports of BRIEF and NeuroQoL Cognitive Function, for which they scored within expected score ranges for adults. Those who were carriers were below average (SD, 1.5) in executive function, measured by Flanker Inhibitory Control and Attention.
The study included 30 subjects with DMD, who were a mean age of 11.4 years (range, 6—16), and 25 biological mothers, who were a mean age of 41.7 years (range, 29–52). In total, 11 mothers were DMD carriers and 8 were not, while 3 did not have data. Another 3 reported knowledge of their status as a carrier. As for DMD mutations, 18 subjects had a deletion, 11 had nonsense, and 1 had duplication.
Of the 30 subjects, 26 were currently on oral corticosteroids (deflazacort, n = 19; prednisone, n = 6; currently enrolled in a double‐blind trial of deflazacort and prednisone, n = 1). Two subjects were not on oral corticosteroids and data were missing in another 2 subjects.
1. Thangarajh M, Kaat AJ, Bibat G, et al. The NIH Toolbox for cognitive surveillance in Duchenne muscular dystrophy. Ann Clin Trans Neurol. Published online August 31, 2019. doi: 10.1002/acn3.50867.
2. Deboer JW, Nicholls C, Corte C, Chestnut K. National Institutes of Health Toolbox Cognition Battery. Arch Clin Neuropsychol. 2014;29(7):692—694. doi: 10.1093/arclin/acu033.