Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention: study protocol for a randomized controlled trial

Aida Bikic, James F Leckman, Jane Lindschou, Torben Ø Christensen, Søren Dalsgaard, Aida Bikic, James F Leckman, Jane Lindschou, Torben Ø Christensen, Søren Dalsgaard

Abstract

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals continue to have difficulties with cognitive functions despite medical treatment, and up to 30 % do not respond to pharmacological treatment. Inadequate medical compliance and the long-term effects of treatment make it necessary to explore nonpharmacological and supplementary treatments for ADHD. Treatment of cognitive dysfunctions may prove particularly important because of the impact of these dysfunctions on the ability to cope with everyday life. Lately, several trials have shown promising results for cognitive computer training, often referred to as cognitive training, which focuses on particular parts of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions.

Methods/design: This multicenter randomized clinical superiority trial aims to investigate the effect of "ACTIVATE™," a computer program designed to improve a range of cognitive skills and ADHD symptoms. A total of 122 children with ADHD, aged 6 to 13 years, will be randomized to an intervention or a control group. The intervention group will be asked to use ACTIVATE™ at home 40 minutes per day, 6 days per week for 8 weeks. Both intervention and control group will receive treatment as usual. Outcome measures will assess cognitive functions, symptoms, and behavioral and functional measures before and after the 8 weeks of training and in a 12- and 24-week follow-up.

Discussion: Results of this trial will provide useful information on the effectiveness of computer training focusing on several cognitive functions. Cognitive training has the potential to reduce cognitive dysfunctions and to become a new treatment option, which can promote a more normal neural development in young children with ADHD and thus reduce cognitive dysfunctions and symptoms. This could help children with ADHD to perform better in everyday life and school.

Trial registration: ClinicalTrials.gov: NCT01752530 , date of registration: 10 December 2012.

Figures

Fig. 1
Fig. 1
CONSORT 2010 Flow Diagram. Flow diagram of participant enrollment and randomization in the trial
Fig. 2
Fig. 2
Timeline of the study enrollment. Timeline of participant assessments in the trial. 1) SDQ, Strength and Difficulties Questionnaire; 2) DAWBA, Development and Well-being Assessment; 3) K-SADS, Kiddie-Schedule for Affective Disorders and Schizophrenia; 4) RIAS, Reynolds Intellectual Assessment Scales; 5) CANTAB, Cambridge Automated Neurocognitive Test Battery; 6) ADHD-RS, Attention Deficit Hyperactivity Disorder-Rating Scale; 7) BRIEF, Behavior Rating Inventory of Executive Functions; 8) WFIRS-P, Weis’s scale of disability-Parent Report; and 9) TAU, treatment as usual

References

    1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM-IV-TR). 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders (5th edition) Arlington: American Psychiatric Publishing; 2013.
    1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164:942–8. doi: 10.1176/appi.ajp.164.6.942.
    1. Dalsgaard S, Nielsen HS, Simonsen M. Consequences of ADHD medication use for children’s outcomes. J Health Econ. 2014;37:137–51. doi: 10.1016/j.jhealeco.2014.05.005.
    1. Massetti GM, Lahey BB, Pelham WE, Loney J, Ehrhardt A, Lee SS, et al. Academic achievement over 8 years among children who met modified criteria for attention-deficit/hyperactivity disorder at 4–6 years of age. J Abnorm Child Psychol. 2008;36:399–410. doi: 10.1007/s10802-007-9186-4.
    1. Dalsgaard S, Mortensen PB, Frydenberg M, Thomsen PH. ADHD, stimulant treatment in childhood and subsequent substance abuse in adulthood - a naturalistic long-term follow-up study. Addict Behav. 2014;39:325–8. doi: 10.1016/j.addbeh.2013.09.002.
    1. Madsen AG, Dalsgaard S. Prevalence of smoking, alcohol and substance use among adolescents with attention-deficit/hyperactivity disorder in Denmark compared with the general population. Nord J Psychiatry. 2014;68:53–9. doi: 10.3109/08039488.2013.768293.
    1. Dalsgaard S, Mortensen PB, Frydenberg M, Maibing CM, Nordentoft M, Thomsen PH. Association between Attention-Deficit Hyperactivity Disorder in childhood and schizophrenia later in adulthood. Eur Psychiatry. 2014;29:259–63. doi: 10.1016/j.eurpsy.2013.06.004.
    1. Maibing CM, Pedersen CB, Benros ME, Mortensen PB, Dalsgaard S, Nordentoft M. Risk of schizophrenia increases after all child and adolescent psychiatric disorders – a nationwide study, Schizophr Bull. 2014. epub September 5.
    1. Dalsgaard S, Mortensen PB, Frydenberg M, Thomsen PH. Long-term criminal outcome of children with attention deficit hyperactivity disorder. Crim Behav Ment Health. 2013;23:86–98. doi: 10.1002/cbm.1860.
    1. Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry. 1993;50:565–76. doi: 10.1001/archpsyc.1993.01820190067007.
    1. Dalsgaard S, Østergaard SD, Leckman JF, Mortensen PB, Pedersen MG. Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: a nationwide cohort study. Lancet. 2015
    1. Faraone SV. Genetics of childhood disorders: XX. ADHD, Part 4: is ADHD genetically heterogeneous? J Am Acad Child Adolesc Psychiatry. 2000;39:1455–7. doi: 10.1097/00004583-200011000-00022.
    1. Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, et al. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci U S A. 2007;104:19649–54. doi: 10.1073/pnas.0707741104.
    1. Castellanos FX, Lee PP, Sharp W, Jeffries NO, Greenstein DK, Clasen LS, et al. Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA. 2002;288:1740–8. doi: 10.1001/jama.288.14.1740.
    1. Gopin CB, Healey DM. The neural and neurocognitive determinants of ADHD. J Infant Child Adolesc Psychother. 2011;10:13–31. doi: 10.1080/15289168.2011.575700.
    1. Frazier TW, Demaree HA, Youngstrom EA. Meta-analysis of intellectual and neuropsychological test performance in attention-deficit/hyperactivity disorder. Neuropsychology. 2004;18:543–55. doi: 10.1037/0894-4105.18.3.543.
    1. Doyle AE, Willcutt EG, Seidman LJ, Biederman J, Chouinard VA, Silva J, et al. Attention-deficit/hyperactivity disorder endophenotypes. Biol Psychiatry. 2005;57:1324–35. doi: 10.1016/j.biopsych.2005.03.015.
    1. Nigg JT. Neuropsychologic theory and findings in attention-deficit/hyperactivity disorder: the state of the field and salient challenges for the coming decade. Biol Psychiatry. 2005;57(11):1424–35. doi: 10.1016/j.biopsych.2004.11.011.
    1. Ceci SJ, Tishman J. Hyperactivity and incidental memory: evidence for attentional diffusion. Child Dev. 1984;55:2192–203. doi: 10.2307/1129791.
    1. Landau S, Lorch EP, Milich R. Visual attention to and comprehension of television in attention-deficit hyperactivity disordered and normal boys. Child Dev. 1992;63:928–37. doi: 10.2307/1131244.
    1. Hooks K, Milich R, Lorch EP. Sustained and selective attention in boys with attention deficit hyperactivity disorder. J Clin Child Psychol. 1994;23:69–77. doi: 10.1207/s15374424jccp2301_9.
    1. Brodeur DA, Pond M. The development of selective attention in children with attention deficit hyperactivity disorder. J Abnorm Child Psychol. 2001;29:229–39. doi: 10.1023/A:1010381731658.
    1. Nigg JT, Butler KM, Huang-Pollock CL, Henderson JM. Inhibitory processes in adults with persistent childhood onset ADHD. J Consult Clin Psychol. 2002;70:153–7. doi: 10.1037/0022-006X.70.1.153.
    1. Karatekin C. A test of the integrity of the components of Baddeley’s model of working memory in attention-deficit/hyperactivity disorder (ADHD) J Child Psychol Psychiatry. 2004;45:912–26. doi: 10.1111/j.1469-7610.2004.t01-1-00285.x.
    1. McLean A, Dowson J, Toone B, Young S, Bazanis E, Robbins TW, et al. Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder. Psychol Med. 2004;34:681–92. doi: 10.1017/S0033291703001296.
    1. Weiss G, Hechtman LT. Hyperactive children grown up. New York: Guilford; 1993.
    1. Lambek R, Tannock R, Dalsgaard S, Trillingsgaard A, Damm D, Thomsen PH. Executive dysfunction in school-age children with ADHD. J Atten Disord. 2011;15:646–55. doi: 10.1177/1087054710370935.
    1. Swanson J, Baler RD, Volkow ND. Understanding the effects of stimulant medications on cognition in individuals with attention-deficit hyperactivity disorder: a decade of progress. Neuropsychopharmacology. 2011;36:207–26. doi: 10.1038/npp.2010.160.
    1. Waschbusch DA, Hill GP, Lilienfield SO, Jay Lynn S, Lohr JM. Science and pseudoscience in clinical psychology. New York: Guilford Press; 2003. Empirically supported, promising and unsupported treatments for children with Attention-Deficit/Hyperactivity Disorder.
    1. Swanson JM, Volkow ND. Psychopharmacology: concepts and opinions about the use of stimulant medications. J Child Psychol Psychiatry. 2009;50:180–93. doi: 10.1111/j.1469-7610.2008.02062.x.
    1. Molina BS, Hinshaw SP, Swanson JM, Arnold LE, Vitiello B, Jensen PS, et al. The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry. 2009;48:484–500. doi: 10.1097/CHI.0b013e31819c23d0.
    1. Johnston MV, Ishida A, Ishida WN, Matsushita HB, Nishimura A, Tsuji M. Plasticity and injury in the developing brain. Brain Dev. 2009;31:1–10. doi: 10.1016/j.braindev.2008.03.014.
    1. Rapoport JL, Gogtay N. Brain neuroplasticity in healthy, hyperactive and psychotic children: insights from neuroimaging. Neuropsychopharmacology. 2008;33:181–97. doi: 10.1038/sj.npp.1301553.
    1. Olesen PJ, Westerberg H, Klingberg T. Increased prefrontal and parietal activity after training of working memory. Nat Neurosci. 2004;7:75–9. doi: 10.1038/nn1165.
    1. Castellanos FX, Giedd JN, Marsh WL, Hamburger SD, Vaituzis AC, Dickstein DP, et al. Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:607–16. doi: 10.1001/archpsyc.1996.01830070053009.
    1. Filipek PA, Semrud-Clikeman M, Steingard RJ, Renshaw PF, Kennedy DN, Biederman J. Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology. 1997;48:589–601. doi: 10.1212/WNL.48.3.589.
    1. Klingberg T, Fernell E, Olesen PJ, Johnson M, Gustafsson P, Dahlström K, et al. Computerized training of working memory in children with ADHD--a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry. 2005;44:177–86. doi: 10.1097/00004583-200502000-00010.
    1. Kerns KA, Eso K, Thomson J. Investigation of a direct intervention for improving attention in young children with ADHD. Dev Neuropsychol. 1999;16:273–95. doi: 10.1207/S15326942DN1602_9.
    1. Murray DW, Skinner AT, Malone PS. A randomized trial of two promising computer-based interventions for students with attention difficulties J Abnorm Child Psychol. 2010 Jan;38(1):131-42. doi:10.1007/s10802-009-9353-x.
    1. Johnstone SJ, Roodenrys S, Blackman R, Johnston E, Loveday K, Mantz S, et al. Neurocognitive training for children with and without AD/HD. Atten Defic Hyperact Disord. 2012;4:11–23. doi: 10.1007/s12402-011-0069-8.
    1. Shinaver CS, 3rd, Entwistle PC, Soderqvist S. Cogmed WM training: reviewing the reviews. Appl Neuropsychol Child. 2014;3:163–72. doi: 10.1080/21622965.2013.875314.
    1. Shipstead Z, Redick TS, Engle RW. Is working memory training effective? Psychol Bull. 2012;138:628–54. doi: 10.1037/a0027473.
    1. Shipstead Z, Hicks KL, Engle RW. Cogmed working memory training: does the evidence support the claims? J Appl Res Mem Cogn. 2012;1:185–93. doi: 10.1016/j.jarmac.2012.06.003.
    1. Melby-Lervag M, Hulme C. Is working memory training effective? A meta-analytic review. Dev Psychol. 2013;49:270–91. doi: 10.1037/a0028228.
    1. Gray SA, Chaban P, Martinussen R, Goldberg R, Gotlieb H, Kronitz R, et al. Effects of a computerized working memory training program on working memory, attention, and academics in adolescents with severe LD and comorbid ADHD: a randomized controlled trial. J Child Psychol Psychiatry. 2012;53:1277–84. doi: 10.1111/j.1469-7610.2012.02592.x.
    1. Chacko A, Bedard AC, Marks DJ, Feirsen N, Uderman JZ, Chimiklis A, et al. A randomized clinical trial of Cogmed Working Memory Training in school-age children with ADHD: a replication in a diverse sample using a control condition. J Child Psychol Psychiatry. 2014;55:247–55. doi: 10.1111/jcpp.12146.
    1. Redick TS, Shipstead Z, Harrison TL, Hicks KL, Fried DE, Hambrick DZ, et al. No evidence of intelligence improvement after working memory training: a randomized, placebo-controlled study. J Exp Psychol Gen. 2013;142:359–79. doi: 10.1037/a0029082.
    1. van der Oord S, Ponsioen AJ, Geurts HM, Ten Brink EL, Prins PJ. A pilot study of the efficacy of a computerized executive functioning remediation training with game elements for children with ADHD in an outpatient setting: outcome on parent- and teacher-rated executive functioning and ADHD behavior. J Atten Disord. 2014;18:699–712. doi: 10.1177/1087054712453167.
    1. Semrud-Clikeman M, Nielsen KH, Clinton A, Sylvester L, Parle N, Connor RT. An intervention approach for children with teacher- and parent-identified attentional difficulties. J Learn Disabil. 1999;32:581–90. doi: 10.1177/002221949903200609.
    1. Chevalier N, Poissant H, Bergeron H, Girard-Lajoie A. The effect of visual-motor imagery training on CPT performance in children with attention deficit hyperactivity disorder. J Cogn Educ Psychol. 2003;3:120–36. doi: 10.1891/194589503787383091.
    1. Tamm L, Epstein JN, Peugh JL, Nakonezny PA, Hughes CW. Preliminary data suggesting the efficacy of attention training for school-aged children with ADHD. Dev Cogn Neurosci. 2012
    1. Shalev L, Tsal Y, Mevorach C. Computerized progressive attentional training (CPAT) program: effective direct intervention for children with ADHD. Child Neuropsychol. 2007;13:382–8. doi: 10.1080/09297040600770787.
    1. Steiner NJ, Sheldrick RC, Gotthelf D, Perrin EC. Computer-based attention training in the schools for children with attention deficit/hyperactivity disorder: a preliminary trial. Clin Pediatr (Phila) 2011;50:615–22. doi: 10.1177/0009922810397887.
    1. Hoekzema E, Carmona S, Tremols V, Gispert JD, Guitart M, Fauquet J, et al. Enhanced neural activity in frontal and cerebellar circuits after cognitive training in children with attention-deficit/hyperactivity disorder. Hum Brain Mapp. 2010;31:1942–50. doi: 10.1002/hbm.20988.
    1. Hoekzema E, Carmona S, Ramos-Quiroga JA, Barba E, Bielsa A, Tremols V, et al. Training-induced neuroanatomical plasticity in ADHD: a tensor-based morphometric study. Hum Brain Mapp. 2011;32:1741–9. doi: 10.1002/hbm.21143.
    1. Buschkuehl M, Hernandez-Garcia L, Jaeggi SM, Bernard JA, Jonides J. Neural effects of short-term training on working memory. Cogn Affect Behav Neurosci. 2014;14:147–60. doi: 10.3758/s13415-013-0244-9.
    1. Obel C, Dalsgaard S, Stax HP, Bilenberg N. Strengths and Difficulties Questionnaire (SDQ-Dan). A new instrument for psychopathologic screening of children aged 4–16 years. Ugeskr Laeger. 2003;165:462–5.
    1. Goodman R, Ford T, Simmons H, Gatward R, Meltzer H. Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample. The British Journal of Psychiatry Dec. 2000:177(6);534-539; doi:10.1192/bjp.177.6.534.
    1. Goodman R, Ford T, Richards H, Gatward R, Meltzer H. The development and well-being assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. J Child Psychol Psychiatry. 2000;41(5):645–55. doi: 10.1111/j.1469-7610.2000.tb02345.x.
    1. Goodman R. The strengths and difficulties questionnaire: a research note. J Child Psychol Psychiatry. 1997;38:581–6. doi: 10.1111/j.1469-7610.1997.tb01545.x.
    1. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980–8. doi: 10.1097/00004583-199707000-00021.
    1. Reynolds R, Kamphaus C. Reynolds intellectual assessment scales and Reynolds intellectual screening test professional manual. Lutz, FL: Psychological Assessment Resources. 2003.
    1. Luciana M. Practitioner review: computerized assessment of neuropsychological function in children: clinical and research applications of the Cambridge Neuropsychological Testing Automated Battery (CANTAB) J Child Psychol Psychiatry. 2003;44:649–63. doi: 10.1111/1469-7610.00152.
    1. Gau SS, Chiu CD, Shang CY, Cheng AT, Soong WT. Executive function in adolescence among children with attention-deficit/hyperactivity disorder in Taiwan. J Dev Behav Pediatr. 2009;30:525–34. doi: 10.1097/DBP.0b013e3181c21c97.
    1. De Luca CR, Wood SJ, Anderson V, Buchanan JA, Proffitt TM, Mahony K, et al. Normative data from the CANTAB. I: development of executive function over the lifespan. J Clin Exp Neuropsychol. 2003;25:242–54. doi: 10.1076/jcen.25.2.242.13639.
    1. DuPaul GJ, Reid R, Anastopoulos AD, Lambert MC, Watkins MW, Power TJ. Parent ratings of attention-deficit/hyperactivity disorder symptoms: factor structure and normative data. J Psychopathol Behav Assess. 1998;20:83–102. doi: 10.1023/A:1023087410712.
    1. Gioia GA, Isquith PK, Guy SC, Kenworthy L. Behavior rating inventory of executive function. Child Neuropsychol. 2000;6:235–8. doi: 10.1076/chin.6.3.235.3152.
    1. Krabbendam L, Aleman A. Cognitive rehabilitation in schizophrenia: a quantitative analysis of controlled studies. Psychopharmacology (Berl) 2003;169:376–82. doi: 10.1007/s00213-002-1326-5.
    1. McGurk SR, Mueser KT. Cognitive functioning, symptoms, and work in supported employment: a review and heuristic model. Schizophr Res. 2004;70:147–73. doi: 10.1016/j.schres.2004.01.009.
    1. Dmitrienko A, Tamhane AC, Bretz F. Multiple testing problems in pharmaceutical statistics. Boca Raton, FL: Chapman and Hall/CRC; 2009.
    1. Jakobsen JC, Gluud C, Winkel P, Lange T, Wetterslev J. The thresholds for statistical and clinical significance - a five-step procedure for evaluation of intervention effects in randomised clinical trials. BMC Med Res Methodol. 2014;14:34. doi: 10.1186/1471-2288-14-34.
    1. DeMets DL, Lan KK. Interim analysis: the alpha spending function approach. Stat Med. 1994;13:1341–52. doi: 10.1002/sim.4780131308.
    1. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61:763–9. doi: 10.1016/j.jclinepi.2007.10.007.
    1. Thorlund K, Engstrøm J, Wetterslev J, Brok J, Imberger G, Gluud C, et al. User manual for trial sequential analysis (TSA) Copenhagen: Copenhagen Trial Unit, Centre for Clinical Intervention Research; 2011.
    1. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative metaanalysis. J Clin Epidemiol. 2008;61:64–75. doi: 10.1016/j.jclinepi.2007.03.013.
    1. Higgins JPT, GS. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration. . Access October 13 2015.
    1. Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L. Industry sponsorship and research outcome. Cochrane Database Syst Rev. 2012;12:MR000033.
    1. Savovic J, Jones H, Altman D, Harris R, Jűni P, Pildal J, et al. Influence of reported study design characteristics on intervention effect estimates from randomised controlled trials: combined analysis of meta-epidemiological studies. Health Technol Assess. 2012;16:1–82. doi: 10.3310/hta16350.
    1. Wood L, Egger M, Gluud LL, Schulz KF, Jüni P, Altman DG, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ. 2008;336:601–5. doi: 10.1136/.
    1. Dalsgaard S, Humlumb MK, Nielsen HS, Simonsen M. Common Danish standards in prescribing medication for children and adolescents with ADHD. Eur Child Adolesc Psychiatry. 2014;23:841–4. doi: 10.1007/s00787-013-0508-5.
    1. Dalsgaarda S, Humlumb MK, Nielsenb HS, Simonsenb M. Relative standards in ADHD diagnoses: the role of specialist behavior. Econ Lett. 2012;117:663–5. doi: 10.1016/j.econlet.2012.08.008.
    1. Dalsgaard S, Nielsen HS, Simonsen M. Five-fold increase in national prevalence rates of attention-deficit/hyperactivity disorder medications for children and adolescents with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other psychiatric disorders: a Danish register-based study. J Child Adolesc Psychopharmacol. 2013;23:432–9. doi: 10.1089/cap.2012.0111.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa