Exploring computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD): protocol for a randomised feasibility study

Emma Yhnell, Hannah Furby, Rachel S Breen, Lucy C Brookes-Howell, Cheney J G Drew, Rebecca Playle, Gareth Watson, Claudia Metzler-Baddeley, Anne E Rosser, Monica E Busse, Emma Yhnell, Hannah Furby, Rachel S Breen, Lucy C Brookes-Howell, Cheney J G Drew, Rebecca Playle, Gareth Watson, Claudia Metzler-Baddeley, Anne E Rosser, Monica E Busse

Abstract

Background: Cognitive impairments, especially deficits of executive function, have been well documented as a core and early feature in Huntington's disease (HD). Cognitive impairments represent considerable burden and can be devastating for people and families affected by HD. Computerised cognitive training interventions that focus on improving executive function present a possible non-pharmacological treatment option. We propose to determine the feasibility, acceptability, and appropriate outcome measures for use in a randomised controlled feasibility study.

Methods/design: Participants will be randomised into either a computerised cognitive training group or a control group. Those randomised to the training group will be asked to complete a cognitive training intervention based on the HappyNeuron Pro software tasks of executive function, for a minimum of 30 min, three times a week for the 12-week study duration. Participants in the control group will not receive computerised cognitive training but will receive a similar degree of social interaction via equivalent study and home visits. We will explore quantitative outcome measures, including measures of cognitive performance, motor function, questionnaires and semi-structured interviews, as well as magnetic resonance imaging (MRI) measures in a subset of participants. Feasibility will be determined through assessment of recruitment, retention, adherence and acceptability of the intervention.

Discussion: The results of this study will provide crucial guidance and information regarding the feasibility of conducting a randomised controlled study into computerised cognitive training in HD. This study is crucial for the development of larger definitive randomised controlled trials which are powered to determine efficacy and for the development of future cognitive training programmes for people affected by HD.

Trial registration: The study is registered on clinicaltrials.gov and has the unique identifier NCT02990676.

Keywords: Cognition; Computerised cognitive training; Feasibility study; Huntington’s disease.

Conflict of interest statement

A favourable ethical opinion for this study was given by Wales Research Ethics Committee (REC) 1 reference number 16/WA/0322 on 2nd December 2016.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Schematic representation of feasibility study

References

    1. MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72(6):971–983. doi: 10.1016/0092-8674(93)90585-E.
    1. Diamond R, White RF, Myers RH, Mastromauro C, Koroshetz WJ, Butters N, et al. Evidence of presymptomatic cognitive decline in Huntington’s disease. J Clin Exp Neuropsychol. 1992;14(6):961–975. doi: 10.1080/01688639208402547.
    1. Gusella JF, Macdonald ME, Duff K, Paulsen JS, Beglinger LJ, Langbehn DR, et al. Psychiatric symptoms in Huntington’s disease before diagnosis: the predict-HD study. Commentary. Biol Psychiatry. 2007;62(12).
    1. Paulsen J, Langbehn D, Stout J, Aylward E, Ross C, Nance M, et al. Detection of Huntington’s disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry. 2008;79(8):874–880. doi: 10.1136/jnnp.2007.128728.
    1. Reiner A, Albin RL, Anderson KD, D'Amato CJ, Penney JB, Young AB. Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci. 1988;85(15):5733–5737. doi: 10.1073/pnas.85.15.5733.
    1. Tabrizi SJ, Langbehn DR, Leavitt BR, Roos RA, Durr A, Craufurd D, et al. Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. The Lancet Neurology. 2009;8(9):791–801. doi: 10.1016/S1474-4422(09)70170-X.
    1. Tabrizi SJ, Scahill RI, Durr A, Roos RA, Leavitt BR, Jones R, et al. Biological and clinical changes in premanifest and early stage Huntington’s disease in the TRACK-HD study: the 12-month longitudinal analysis. The Lancet Neurology. 2011;10(1):31–42. doi: 10.1016/S1474-4422(10)70276-3.
    1. Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington’s disease in the TRACK-HD study: analysis of 36-month observational data. The Lancet Neurology. 2013;12(7):637–649. doi: 10.1016/S1474-4422(13)70088-7.
    1. Helder D, Kaptein A, Van Kempen G, Van Houwelingen J, Roos R. Impact of Huntington’s disease on quality of life. Mov Disord. 2001;16(2):325–330. doi: 10.1002/mds.1056.
    1. Ready RE, Mathews M, Leserman A, Paulsen JS. Patient and caregiver quality of life in Huntington’s disease. Mov Disord. 2008;23(5):721–726. doi: 10.1002/mds.21920.
    1. Delval A, Krystkowiak P, Delliaux M, Dujardin K, Blatt JL, Destée A, et al. Role of attentional resources on gait performance in Huntington’s disease. Mov Disord. 2008;23(5):684–689. doi: 10.1002/mds.21896.
    1. Thompson JC, Poliakoff E, Sollom AC, Howard E, Craufurd D, Snowden JS. Automaticity and attention in Huntington’s disease: when two hands are not better than one. Neuropsychologia. 2010;48(1):171–178. doi: 10.1016/j.neuropsychologia.2009.09.002.
    1. Trueman RC, Brooks SP, Jones L, Dunnett SB. The operant serial implicit learning task reveals early onset motor learning deficits in the HdhQ92 knock-in mouse model of Huntington’s disease. Eur J Neurosci. 2007;25(2):551–558. doi: 10.1111/j.1460-9568.2007.05307.x.
    1. Trueman RC, Dunnett SB, Jones L, Brooks SP. Five choice serial reaction time performance in the Hdh Q92 mouse model of Huntington’s disease. Brain Res Bull. 2012;88(2):163–170. doi: 10.1016/j.brainresbull.2011.10.019.
    1. Curtin PC, Farrar AM, Oakeshott S, Sutphen J, Berger J, Mazzella M, et al. Cognitive training at a young age attenuates deficits in the zQ175 mouse model of HD. Front Behav Neurosci. 2015;9:1-13.
    1. Yhnell E, Lelos MJ, Dunnett SB, Brooks SP. Cognitive training modifies disease symptoms in a mouse model of Huntington’s disease. Exp Neurol. 2016;282:19–26. doi: 10.1016/j.expneurol.2016.05.008.
    1. Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M, et al. Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA. 2002;288(18):2271–2281. doi: 10.1001/jama.288.18.2271.
    1. Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006;296(23):2805–2814. doi: 10.1001/jama.296.23.2805.
    1. Melby-Lervåg M, Redick TS, Hulme C. Working memory training does not improve performance on measures of intelligence or other measures of “far transfer” evidence from a meta-analytic review. Perspect Psychol Sci. 2016;11(4):512–534. doi: 10.1177/1745691616635612.
    1. Metzler-Baddeley C, Cantera J, Coulthard E, Rosser A, Jones DK, Baddeley RJ. Improved executive function and callosal white matter microstructure after rhythm exercise in Huntington’s disease. Journal of Huntington's disease. 2014;3(3):273–283.
    1. Clare L, Woods R, Moniz Cook E, Orrell M, Spector A. Cognitive rehabilitation and cognitive training for early-stage Alzheimer’s disease and vascular dementia. Cochrane Database Syst Rev. 2003;4.
    1. Davis RN, Massman PJ, Doody RS. Cognitive intervention in Alzheimer disease: a randomized placebo-controlled study. Alzheimer Dis Assoc Disord. 2001;15(1):1–9. doi: 10.1097/00002093-200101000-00001.
    1. Farina E, Fioravanti R, Chiavari L, Imbornone E, Alberoni M, Pomati S, et al. Comparing two programs of cognitive training in Alzheimer’s disease: a pilot study. Acta Neurol Scand. 2002;105(5):365–371. doi: 10.1034/j.1600-0404.2002.01086.x.
    1. Milman U, Atias H, Weiss A, Mirelman A, Hausdorff JM. Can cognitive remediation improve mobility in patients with Parkinson’s disease? Findings from a 12 week pilot study. Journal of Parkinson's disease. 2014;4(1):37–44.
    1. Sammer G, Reuter I, Hullmann K, Kaps M, Vaitl D. Training of executive functions in Parkinson’s disease. J Neurol Sci. 2006;248(1):115–119. doi: 10.1016/j.jns.2006.05.028.
    1. Sinforiani E, Banchieri L, Zucchella C, Pacchetti C, Sandrini G. Cognitive rehabilitation in Parkinson’s disease. Arch Gerontol Geriatr. 2004;38:387–391. doi: 10.1016/j.archger.2004.04.049.
    1. Sadeghi M, Barlow-Krelina E, Gibbons C, Shaikh KT, WLA F, Meschino WS, et al. Feasibility of computerized working memory training in individuals with Huntington disease. PLoS One. 2017;12(4):e0176429. doi: 10.1371/journal.pone.0176429.
    1. Caeyenberghs K, Metzler-Baddeley C, Foley S, Jones DK. Dynamics of the human structural connectome underlying working memory training. J Neurosci. 2016;36(14):4056–4066. doi: 10.1523/JNEUROSCI.1973-15.2016.
    1. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. Pilot and feasibility studies. 2016;2(1):64. doi: 10.1186/s40814-016-0105-8.
    1. Tarpin-Bernard F, Croisile B. Conditions for maximizing effects of 90 days of brain training. Scientific Brain Training. 2012. .
    1. Bowie CR, SR MG, Mausbach B, Patterson TL, Harvey PD. Combined cognitive remediation and functional skills training for schizophrenia: effects on cognition, functional competence, and real-world behavior. Am J Psychiatry. 2012;169(7):710-8. 10.1176/appi.ajp.2012.11091337.
    1. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31(1):103–15.
    1. Salthouse TA. When does age-related cognitive decline begin? Neurobiol Aging. 2009;30(4):507–514. doi: 10.1016/j.neurobiolaging.2008.09.023.
    1. Ardila A, Ostrosky-Solis F, Rosselli M, Gómez C. Age-related cognitive decline during normal aging: the complex effect of education. Arch Clin Neuropsychol. 2000;15(6):495–513. doi: 10.1093/arclin/15.6.515.
    1. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chiro G. Diffusion tensor MR imaging of the human brain. Radiology. 1996;201(3):637–648. doi: 10.1148/radiology.201.3.8939209.
    1. Zhang H, Schneider T, Wheeler-Kingshott CA, Alexander DC. NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. NeuroImage. 2012;61(4):1000–1016. doi: 10.1016/j.neuroimage.2012.03.072.
    1. Cercignani M, Alexander DC. Optimal acquisition schemes for in vivo quantitative magnetization transfer MRI. Magn Reson Med. 2006;56(4):803–810. doi: 10.1002/mrm.21003.
    1. Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A Bayesian model of shape and appearance for subcortical brain segmentation. NeuroImage. 2011;56(3):907–922. doi: 10.1016/j.neuroimage.2011.02.046.
    1. Alsop DC, Detre JA, Golay X, Günther M, Hendrikse J, Hernandez-Garcia L, et al. Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magn Reson Med. 2015;73(1):102–116. doi: 10.1002/mrm.25197.
    1. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77–101. doi: 10.1191/1478088706qp063oa.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8(1):18. doi: 10.1186/1741-7015-8-18.
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. doi: 10.1136/bmj.e7586.

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