Longitudinal Evaluation of Working Memory in Duchenne Muscular Dystrophy

Abstract

Objective: The developmental maturation of forward and backward digit spans—indices of working memory—in boys with nonsense (nm) Duchenne muscular dystrophy (DMD) (nmDMD) was assessed using prospective, longitudinal data. Methods: Fifty-five boys of the 57 subjects with genetically confirmed nmDMD—who were from the placebo arm of a 48-week-long phase 2b clinical trial—were evaluated. Forward and backward digit spans were obtained every 12 weeks for a total of five assessments in all study subjects. Changes in forward and backward digit spans were evaluated based on age, corticosteroid treatment, and DMD mutation location. Results: Boys with nmDMD had lower mean scores on normalized forward digit span. Normalized forward digit spans were comparable between subjects stratified by age and between corticosteroid-naïve and corticosteroid-treated subjects. When stratified by DMD mutation location, normalized forward digit spans were lower in nmDMD subjects with mutations downstream of DMD exon 30, exon 45, and exon 63, both at baseline evaluation and at follow-up evaluation at 48 weeks. On average, normalized backward digit span scores were stable over 48 weeks in these subjects. Developmental growth modeling showed that subjects with nmDMD mutations upstream of DMD exon 30, upstream of DMD exon 45, and upstream of DMD exon 63 appeared to make better gains in working memory than subjects with mutations downstream of DMD exon 30, downstream of DMD exon 45, and downstream of DMD exon 63. Conclusion: Performance in working memory shows deficits in nmDMD and differed based on nmDMD location. Maturation in cognition was seen over a 48-week period. The developmental trajectory of working memory in this cohort was influenced by DMD mutation location.

Wechsler Scale Intelligence Testing in Males with Dystrophinopathies: A Review and Meta-Analysis

“…A third author (JH) was involved to solve two disagreements. Forty-seven full-text articles were excluded for diverse reasons (e.g., the study did not use Wechsler Intelligence scales) [ 12 , 14 , 16 , 18 , 21 , 28 , 29 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ] and 43 studies were included in the meta-analysis [ 10 , 11 , 13 , 19 , 20 , …”

“…In the more recent theoretical models on intelligence (CHC model; WPPSI-IV, WISC-V and WAIS-V) the VIQ/PIQ structure is abandoned and exchanged for more specific intelligence index scores such as working memory. This an important domain to study within the DMD population since (verbal) working memory problems have been previously reported [ 51 , 80 , 125 ].…”

Complexity of skeletal muscle degeneration: multi-systems pathophysiology and organ crosstalk in dystrophinopathy

“…Different degrees of neurodevelopmental, psychiatric, behavioural and emotional symptoms have been clearly established in a subset of individuals suffering from severe forms of dystrophinopathy [ 61 ] but can also occur in more benign cases of Becker muscular dystrophy [ 173 ]. Neurological issues are characterised by social, behavioural and emotional problems [ 129 , 275 ], delayed milestones of language development [ 58 ], adaptive deficiencies [ 57 ], impaired working memory [ 336 ] and a variety of neuropsychiatric diseases such as hyperactivity, obsessive–compulsive behaviour, attention deficit and autism spectrum disorders [ 128 , 257 , 258 ]. However, it is important to emphasise that severe cognitive impairments and mental retardation occur only in a subgroup of patients and were shown to be secondary in nature to physical handicap [ 210 , 311 ].…”

Características Cognitivas e Comportamentais Associadas à Distrofia Muscular de Duchenne: Revisão Integrativa

“…A condição é causada por diferentes mutações que atingem o gene DMD e que levam à ausência da proteína distrofina, maior produto do gene. Sua ausência leva à degeneração irreversível do tecido muscular e acarreta em fraqueza muscular progressiva (Fu et al, 2016), perda da capacidade de deambular por volta do início da adolescência e em comprometimentos respiratórios e cardíacos (Colombo et al, 2017;Thangarajh et al, 2020;Tyagi et al, 2021).…”

“…Aponta-se, ainda, para maior prevalência de determinados transtornos do neurodesenvolvimento como Deficiência Intelectual (DI), Transtorno do Espectro Autista (TEA), Transtorno de Déficit de Atenção e Hiperatividade (TDAH), além de problemas internalizantes e externalizantes de comportamento (Ricotti, Mandy, Scoto, et al, 2016). Apesar de a produção de conhecimento relacionado a esses tópicos ser crescente, os aspectos neuropsicológicos e neurocomportamentais são acessados com menos frequência, em comparação aos estudos voltados para os impactos neuromusculares da DMD (Thangarajh et al, 2020). A observação de alteração e de déficits nos campos cognitivo e comportamental apontam para a necessidade de se priorizar, também, a investigação desses componentes (Snow et al, 2013).…”