Verbal and memory skills in males with Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a progressive pediatric disorder that affects both muscle and brain. Children with DMD have mean IQ scores that are about one standard deviation lower than population means, with lower Verbal IQ than Performance IQ scores. For the present study, verbal skills and verbal memory skills were examined in males with DMD with the Clinical Evaluation of Language Fundamentals, 3rd edition, and the California Verbal Learning Test for Children. Performance of 50 males with DMD (age range 6-14y, mean 9y 4mo [SD 2y 1mo]) was compared to normative values. Two subsets of the probands were also compared with two comparison groups: unaffected siblings (n=24; DMD group age range 6-12y, mean 9y 1mo [SD 1y 8mo]; sibling age range 6-15y, mean 9y 11mo [SD 2y 4mo]) and males with cerebral palsy (CP);(n=23; DMD group age range 6-9y, mean 7y 8mo [SD 1y 2mo]; CP age range 6-8y, mean 6y 8mo [SD 0y 8mo]). Results demonstrated that although males with DMD performed slightly more poorly than normative values, they performed comparably to the controls on most measures. Consistent deficits were observed only on tests requiring immediate repetition for verbal material (Recalling Sentences, and Concepts and Directions). On other language tasks, including tests of understanding and use of grammar, and understanding of semantic relationships, the males with DMD performed well. Moreover, the males with DMD performed well on multiple indices of verbal recall, and there was no evidence of declarative memory deficits. DMD is a single-gene disorder that is selectively associated with decreased verbal span capacity, but not impaired recall.The cognitive presentation in Duchenne muscular dystrophy (DMD) is intriguing. Ever since its original characterization by Duchenne, 1 the illness has been known to be associated with 'dull' intellect and 'difficult' speech in some affected individuals, yet most do not have significant cognitive complaints. DMD presents with progressive physical disability and a shortened lifespan. DMD is primarily a disease of muscle, yet it also affects the central nervous system. Individuals with DMD have a genetic mutation that prevents the production of the protein product dystrophin, and of multiple dystrophin isoforms. In muscle, lack of dystrophin results in unstable muscle cell membranes that break down over time, causing progressive weakness. In the brain, a lack of dystrophin isoforms has been documented in the cerebral cortex and cerebellum, in specific cell types (especially pyramidal and Purkinje cells) and in specific cell areas (especially the neuronal postsynaptic densities). 2,3 As a group, children with DMD present with relatively weak verbal and immediate memory skills. [4][5][6][7][8] There is individual variation across factors that contribute to the cognitive phenotype, including intellectual level, age, degree of physical disability, and background environment. The goal of the present study was to explore, in detail, language and verbal memory skills in children with DMD.A...

Diffusion tensor imaging study in Duchenne muscular dystrophy

“…This study recruited 12 patients [age 9.14±2.52 years (range, 6-13)] with a diagnosis of DMD (confirmed by genetic testing or muscle biopsy) from the DMD Multidisciplinary Outpatient Clinic of CAPF General Hospital, and 14 healthy volunteers [age 9.39±2.99 years (range, [6][7][8][9][10][11][12][13][14]]. Those who had a medical or surgical history of potential impact on neurocognitive functioning (e.g., head injury), were not contactable, or whose parents refused to consent were excluded.…”

“…The core cognitive deficit in DMD is "limited verbal span" (6). Some researchers have noted that children with DMD have greater difficulty on tests requiring attention to and repetition of verbal material (6)(7)(8)(9)(10). This finding remains consistent regardless of whether children with DMD are compared to normal controls, their siblings, or children with other degenerative muscle diseases.…”

The dystrophin gene and cognitive function in the general population

“…20,21 We focused on neurocognitive domains which are known to be affected in patients with DMD. [8][9][10][11][12] General cognitive ability was assessed with the Dutch Adult Reading Test (DART). Memory function was measured with a word learning test from which immediate recall and learning scores were derived while executive function was assessed with the Trail Making Test (TMT) parts A and B 22 and verbal fluency tests.…”

“…6 Deficits in short-term memory, executive functions, visuospatial ability, as well as deficits in some aspect of attention, problems with narrative, linguistic and reading skills have been described, irrespective of general intelligence. [7][8][9][10][11][12] Moreover, a higher incidence of different neuropsychiatric disorders, such as autism spectrum, attention deficit hyperactivity disorder, obsessive-compulsive disorders and social behavior problems has been revealed among affected males. [13][14][15][16][17] The impact of DMD on cognitive ability in cognitively healthy populations has not been studied to the best of our knowledge; therefore, in the current study we aim to investigate whether singlenucleotide DMD variants associate with variability in cognitive functions in general populations, suggesting loci in the DMD contributing to cognition, besides genuine DMD variants.…”

Cognitive and adaptive deficits in young children with Duchenne muscular dystrophy (DMD)

“…When asked to recall numbers, sentences, or stories, for example, children with DMD consistently perform more poorly than their matched controls (Anderson et al, 1988;Billard et al, 1992Billard et al, , 1998Dorman et al, 1988;Hinton et al, 2000Hinton et al, , 2001Hinton et al, , 2004Ogasawara, 1989;Whelan, 1987;Wicksell et al, 2004). These findings appear across all intellectual levels, regardless of cognitive functioning (Hinton et al, 2000), and are not due to more general impairments in language and memory (Hinton et al, 2007). Whether limited verbal span reflects weaknesses in attentional or language skills is unclear, but most likely both skills contribute.…”