Background Individuals with fragile X syndrome (FXS) typically demonstrate profound executive function (EF) deficits that interfere with learning, socialization, and emotion regulation. We completed the first large, non-pharmacological controlled trial for FXS, designed to evaluate the efficacy of Cogmed, a computer/tablet-based working memory (WM) training program. Methods The study was a randomized, blinded, parallel two-arm controlled trial in 100 children and adolescents with FXS (63 male, 37 female; 15.28 ± 3.36 yrs.). Participants were randomized equally to adaptive (difficulty level adjusted to performance) or non-adaptive (control) Cogmed training. Participants were assessed at home using objective measures of WM (primary outcome) and EF at baseline, following 20–25 caregiver-supported sessions over 5–6 weeks, and at follow-up 3 months after cessation of training. Parents and teachers provided ratings of WM, attention, and EF. Results The WM composite and selective domains of EF (distractibility, cognitive flexibility), as well as parent- and teacher-reported attention and EF, significantly improved across the full study sample, with many changes maintained at follow-up. However, comparisons of improvement between adaptive and non-adaptive control conditions did not differ, showing that progressively challenging the WM system by expanding span length did not provide added benefit overall. Conclusions Further experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3 months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences (e.g., baseline capacity, training efficiency, co-morbidity, training environment, characteristics of training aide) may help to link this intervention to outcomes and potential transfer effects. Trial registration US National Institutes of Health (ClinicalTrials.gov), NCT02747394 . Electronic supplementary material The online version of this article (10.1186/s11689-019-9264-2) contains supplementary material, which is available to authorized users.

Early-developing cerebellar or fronto-motor tract white matter changes, previously documented in MRI studies, may underlie motor slowing that occurs before clinically observable neurological symptoms associated with FXTAS. © 2018 International Parkinson and Movement Disorder Society.

Children with fragile X syndrome (FXS) exhibit deficits in a variety of cognitive processes within the executive function domain. As working memory (WM) is known to support a wide range of cognitive, learning and adaptive functions, WM computer-based training programs have the potential to benefit people with FXS and other forms of intellectual and developmental disability (IDD). However, research on the effectiveness of WM training has been mixed. The current study is a follow-up “deep dive” into the data collected during a randomized controlled trial of Cogmed (Stockholm, Sweden) WM training in children with FXS. Analyses characterized the training data, identified training quality metrics, and identified subgroups of participants with similar training patterns. Child, parent, home environment and training quality metrics were explored in relation to the clinical outcomes during the WM training intervention. Baseline cognitive level and training behavior metrics were linked to gains in WM performance-based assessments and also to reductions in inattention and other behaviors related to executive functioning during the intervention. The results also support a recommendation that future cognitive intervention trials with individuals with IDD such as FXS include additional screening of participants to determine not only baseline feasibility, but also capacity for training progress over a short period prior to inclusion and randomization. This practice may also better identify individuals with IDD who are more likely to benefit from cognitive training in clinical and educational settings.