Exploring Computerised Cognitive Training for People With Huntington's Disease
Exploring Computerised Cognitive Training for People With Huntington's Disease
Cognitive impairments, especially deficits of executive function, have been well documented
 as a core and early feature in Huntington's disease (HD). Cognitive impairments can be
 considerably burdensome and devastating for people and families affected by HD. Computerised
 cognitive training interventions that focus on improving executive function present a
 potentially exciting non-pharmacological treatment option. Novel work conducted in mouse
 models of HD, has demonstrated that cognitive training, administered from an early stage in
 the disease, can improve motor performance at an older age, even in the absence of further
 training in the intervening time. This represents proof of principle in an animal model of HD
 that cognitive training can improve HD disease symptoms.

 Improvements associated with executive function training have also been reported in a
 clinical setting in a variety of neurodegenerative diseases. For example, cognitive training,
 can improve executive function as people age, and training specifically focused on tasks of
 executive function has been shown to improve both cognitive and motor outcomes in
 neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD).
 Therefore, this study is a feasibility study which aims to establish proof of principle for
 using computerised cognitive training in people with HD. The investigators propose to
 determine the feasibility, acceptability and gather preliminary evidence of the effectiveness
 of a cognitive training intervention programme, targeted for people with HD. The
 investigators will also aim to investigate the most appropriate outcome measures to use in
 this study and gather feedback on the cognitive training intervention. The investigators will
 also establish proof of concept via the study of brain structure and function, using MRI
 scanning techniques.

 The computerised cognitive training software and the associated outcome measures will be
 investigated, taking into account the views of people and families who are affected by HD. A
 randomised feasibility study of computerised cognitive training for people with HD will then
 be conducted. Participants who are randomised to the cognitive training intervention group
 will be asked to complete a cognitive training intervention utilising "HAPPYneuron" software.
 Participants in the intervention group will be asked to complete the cognitive training
 programme for a minimum of 30 minutes, 3 times a week for the 12 week study duration.
 Participants in the control group will not receive any cognitive training and will be asked
 to continue as normal, however they will have home visits to control for the confounding
 effect of social interaction. Additional monitoring and prompting for the intervention group,
 will be conducted via email, text or telephone reminders (as preferred by the participant)
 and home visits. The motor and cognitive function of participants will be assessed at the
 beginning and end of the study, using a range of motor and cognitive assessments. Additional
 cognitive measurements will be recorded as part of the HAPPYneuron programme throughout the
 cognitive training intervention, such as accuracy and response time measures of particular
 computer games. MRI scans (optional) will be conducted at the beginning and end of the study
 to identify any structural changes in the brain that may be associated with the cognitive
 training intervention. As part of the feasibility and acceptability assessment, participants,
 family members and carers will be invited to complete a semi-structured interview at the end
 of the study, if consent is obtained, focusing on using this type of software as a home based
 therapeutic intervention.
Due to space constraints a more extensive description of the research study can be found in
 the study protocol.

 1. Background and Rationale Huntington's disease (HD) is caused by a CAG repeat
 trinucleotide expansion within the first exon of the huntingtin gene and causes a range
 of symptoms including motor, cognitive and psychiatric disturbances, which significantly
 affect daily activities, independence and quality of life, even during the early stages
 of the disease. Cognitive dysfunctions from early on in the HD disease process have been
 well documented and can include specific problems with attention, cognitive flexibility
 and memory. Indeed, difficulty sharing attention between more than one task has been
 demonstrated to be a specific and core deficit in HD.

 Cognitive training interventions, which focus on executive function, present a
 potentially exciting non-pharmacological treatment option for neurodegenerative diseases
 including HD. Studies in HD mice have previously demonstrated executive function
 impairments, including deficits in attention and subsequent studies have shown that
 cognitive training can benefit HD mice and prevent the onset of cognitive and motor
 disease symptoms. This work suggests that an early cognitive training intervention can
 have significant and long-lasting beneficial effects on HD symptoms. Although further
 systematic studies in mouse models of HD are required to inform the translational
 aspects of cognitive training interventions, these results provide important proof of
 principle evidence that cognitive training can provide benefit in mouse models of HD.

 Studies in human populations suggest that cognitive training, via repeatedly conducting
 tasks that require specific aspects of executive function such as attention, reasoning
 and memory, can improve cognitive function as people age. Computerised cognitive
 training studies have also been conducted in a number of neurodegenerative diseases
 including Parkinson's disease (PD) and Alzheimer's disease (AD). These studies have
 found that computerised cognitive training that can improve cognition in PD and AD.
 However, a systematic literature review of Europe PubMed Central using the keywords,
 'Huntington's disease' and 'cognitive training' or 'cognitive therapy' or 'brain
 training' or 'executive function training' conducted from the years 1950 to 2015,
 produced 2 results. A review on cognitive burden in HD and a paper on exercise in a
 mouse model of HD benefiting cognitive symptoms. Thus, the use of cognitive training in
 HD is a considerably under researched area and to our knowledge cognitive training is
 yet to be explored in HD. Therefore, feasibility studies, such as the one proposed in
 this application are crucial in trialing novel potential therapeutic interventions.

 The outcome measures used to determine patient benefit in cognitive training studies can
 vary significantly between studies. Furthermore, this is the first time that such an
 intervention has been used in people with HD. Therefore, the outcome measures used in
 cognitive training studies to determine patient benefit need to be carefully explored
 and defined prior to beginning the study. The candidate outcome measures for use in this
 study have been chosen to include both cognitive and motor measures specific to people
 with HD to best evaluate the outcome of the intervention. Difficulty sharing attention
 has been shown to be a specific problem in HD. Attentional sharing can be measured
 clinically using dual tasks where participants are required to do two tasks at the same
 time. The two tasks can be from the same modality such as walking and carrying a tray,
 or from different modalities such as walking combined with a cognitive component such as
 counting. Dual task studies have shown that people with HD have reduced attentional
 sharing capacity, particularly when the dual task has a cognitive element. As the
 ability to complete dual tasks and increasing attentional demand are key skills in
 everyday life, deficits in such tasks can severely affect independence, increase the
 risk of falls and reduce quality of life. The proposed study will use dual task
 performance to assess feasibility, acceptability and to gather preliminary efficacy data
 on the effect of cognitive training interventions in people with HD.

 Environmental enrichment has been shown to improve disease symptoms in HD mice and a
 retrospective study regarding lifestyle of people with HD suggests that a passive or
 sedentary lifestyle, lacking in enriching activities, may contribute to earlier onset of
 disease symptoms. There is also preliminary evidence that motor training can produce
 functional benefits in HD and accumulating evidence of feasibility and functional
 improvements from both in- and out-patient exercise and rehabilitation programmes. Motor
 training exercise studies have shown that multi-modal exercise interventions are well
 tolerated and associated with improvements in movement, cognition and mood alongside
 increases in health related quality of life. Work is now ongoing to develop methods to
 support and enhance adherence to home exercise in HD. Furthermore, the investigators now
 have preliminary evidence that an intervention with both motor and cognitive components
 (a training regimen in which patients' train to drum increasingly complex rhythms to
 music) can produce improvements on the symbol digit modalities, a test of executive
 function, with accompanying changes on MRI tractography. Brain imaging studies are
 hugely important in greater understanding the biological mechanisms which may underpin
 any intervention in a neurodegenerative disease.

 Strategies for conducting cognitive training can vary between research studies. Some use
 taught exercises or puzzles which participants learn and then repeat. However, the
 utilisation of computerised cognitive training strategies provides several advantages
 over repeating practical tasks. Computerised cognitive training strategies are automated
 and can be completed by participants at their convenience, they provide automated tasks
 which require comparatively little movement to complete and provide several objective
 outcome measures. Furthermore, the specific HAPPYneuron cognitive training software that
 the investigators are using in this study provides an interface for the researcher to
 observe the progress of study participants and it can be made available in different
 languages to allow for consistent training globally. However, as this is a feasibility
 study, the computerised cognitive training intervention will be optimised taking into
 account the feedback and views of people with HD.

 2. Study Aims The primary aim of this study is to determine if computerised cognitive
 training, is feasible and acceptable for people with HD. The researchers will
 investigate the familiarity of participants with the computerised cognitive training
 programme, its usability and determine key outcome measures for use in cognitive
 training studies, before conducting a randomised feasibility study. The randomised
 feasibility study will also explore the biological underpinnings of any observed
 behavioral changes using MRI scanning, this is an optional component of the study.
 During this study, important parameters will be established, which will allow us to
 develop the intervention programme for use in a larger patient cohort.

 2.1. Specific Objectives

 The objectives of the proposed study are to:

 (i) investigate the familiarity of participants ad usability of computerised cognitive
 training programmes and determine key outcome measures for use in cognitive training
 studies.

 (ii) assess the feasibility of delivering a home based computerised cognitive training
 programme for people with HD, considering:

 -  The willingness of eligible participants to receive the intervention and
 participate in a feasibility study (including the feasibility of randomisation)

 -  Potential barriers to recruitment or completion of the study

 -  Response rates and adherence to the cognitive training programme (iii) determine
 any behavioural changes which may occur during the intervention or comparable
 control arm.

 (iv) use brain imaging techniques to explore the biological underpinnings of any
 observed behavioral change (optional).

 (v) evaluate the intervention using participant and family member/carer feedback to
 future use in this patient population.

 3. Study Design Participants will be recruited from the Cardiff Huntington's disease
 Centre. Participants will be asked to complete a range of computer and paper based
 cognitive tasks, motor tasks and interviews in their first research visit, which may
 coincide with their ENROLL-HD visit. Participants will then be invited back to complete
 baseline assessments for the feasibility study within the next 4 weeks. After
 randomisation, those allocated to the intervention group will receive the 12-week
 home-based cognitive training intervention, supported by home visits and email or
 telephone reminders, as preferred. Those allocated to the control group will be asked to
 continue as normal although they will also receive home visits. At 6 weeks an optional
 MRI scan will be conducted in addition to cognitive tasks. 12 weeks after completing
 baseline assessments, participants will be invited back to complete the final outcome
 assessments.

 4. Participant Selection The Cardiff HD Centre is an Enroll-HD (previously Registry) site
 and many patients attending the clinic are enrolled in this study (REC no. 04/WSE05/89).
 Patients already enrolled to a global Enroll-HD observational study will be invited to
 take part in this study. The progression of symptoms in these Enroll-HD participants are
 monitored longitudinally. One of the optional components within the Enroll-HD study is
 the giving of permission by participants to be contacted about other additional and
 affiliated HD research studies, and for their coded data to be accessed by researchers
 conducting HD related research. As such, a full clinical data set including full medical
 and medication history will be available for each research participant and this data may
 be used during the study. In addition, the investigators would like to gather the views
 of family members, friends and carers. Participants will be asked to provide consent so
 that the investigators can talk to their family member, friend or carer, who may be
 attending research visits with the participant, about their involvement in the study. If
 informed consent is obtained, via a participant dated consent form, the family member,
 friend or carer will be invited to be interviewed about the study.

 5. Recruitment 5.1. Number of Participants This is an initial proof of principle study;
 thus no formal sample size calculations have been completed. The investigators will aim
 to recruit 50 participants with a target of randomising 40 participants. The suggested
 numbers are based on previous literature regarding cognitive training in other diseases
 and considering that MRI is an optional component of the study. The study team have
 funds for the MRI scanning of 16 participants during the study, scanning will be
 conducted on a first come first served basis and once the funds for scanning are used no
 further participants will be able to be scanned. This study is an essential step towards
 a larger systematic study of cognitive training and will inform the design and delivery
 of such a trial, as well as providing data to inform a power calculation to estimate
 sample size in the future.

 5.2. Recruitment Process Potential participants, who have already consented to
 participate in ENROLL-HD may be approached during their clinical visits and will be
 informed of the study. Potential participants will receive an information sheet about
 this study and be will be given sufficient time to ask questions and discuss the study
 with the researcher. If required, potential participants can take the information sheets
 home and discuss the study with their family and friends. Potential participants who
 wish to consent will be reminded that they can change their mind or withdraw without
 reason at any time. If the potential participant is willing to proceed with the study,
 they will be asked to sign a consent form and the study assessments will begin.

 5.3. Informed Consent The participant will be allowed as much time as needed to consider
 the Participant Information Sheet (PIS) and the opportunity to question the research
 team or independent parties to decide whether he/she will participate in the study. All
 participants will have the procedures explained in detail, including that the study
 design is randomised, that MRI scanning is an optional component and that they can
 withdraw at any time. Informed consent will then be obtained by means of participant
 dated signature and dated signature of the person who presented and obtained the
 informed consent. The original signed form will be retained at the study site. After
 informed consent has been received the first study visit will take place. Participants
 will be reminded that they can withdraw from the study at any time, without the need to
 give a reason and this will not affect their current or future care. Participants will
 be asked during the consent process if their family member or carer can be asked their
 opinions of cognitive training interventions, this is an optional component of the
 consent form. If consent is provided to ask family members, friends or carers that
 attend the clinic with the participant, they will be asked to read a separate
 information sheet. If they agree to participate, they will be asked to sign a consent
 form and they will then be interviewed regarding the study.

 5.4. Health Checks/Screening Required for Magnetic Resonance Imaging (MRI) Scanning MRI
 scanning is an optional component of the study. Thus, as part of the pre-screening
 process, all participants will be screened for contraindications to MRI. In addition,
 comprehensive screening for MRI contraindications will be completed immediately before
 each MRI scan by the researcher and the MRI operator before the participant is allowed
 into the scanning room.

 5.5. Randomisation Procedures As the study includes an intervention and control group,
 randomisation will be performed using a minimisation procedure and programme to ensure
 balance between the groups for categorical variables of age and cognitive function.
 Minimisation will be performed by the researcher, considering age and cognitive results
 of the most recently published global ENROLL-HD study data. Age and cognitive function
 will be given the same weighting during the minimisation procedure. Age will be
 classified into two categories: 1) < 45 years and 2) > 45 years. The total cognitive
 score of the participant in the Categorical Verbal Fluency Test, will be used to
 classify participants into two categories. The randomisation procedure will be carefully
 explained to all potential research participants and is specifically outlined in both
 the PIS and CF. Randomisation will only be performed after the participant has signed
 the CF and completed the initial and baseline assessments. Participants allocated to the
 control group will be asked to carry on as normal. Once allocated to a group,
 participants will receive an allocation letter detailing the group that they have been
 randomised to. Unfortunately, due to licencing restrictions those allocated to the
 control group will only be able to use the cognitive training software in the first
 research visit and during the baseline and outcome assessments of the second and third
 research visits. It will be made clear to all potential participants at the end of the
 study, they will have to stop using the cognitive training software as their access to
 the login system will expire.

 6. Study Procedures

 6.1 The 12-week Cognitive Training Intervention The 12-week cognitive training
 intervention will be completed in participant homes. The intervention will be supported
 by email, text and telephone reminders (as preferred by the participant and detailed in
 the Case Report Form) and home visits. Home visits will be conducted for both the active
 and control groups. Although additional home visits may be necessary if a participant is
 concerned about using the software. During the research visits, for the active group,
 the researcher will ensure that the participant is comfortable with the software,
 offering support and guidance and a battery of cognitive assessments will be performed.
 For the control group during home visits the researcher will complete the cognitive test
 battery and talk to the participant about their day. The intervention is designed to be
 conducted with minimal supervision and this is something that will be explored during
 participant and friend, family member or carer interviews. When completing home visits,
 the researcher will comply with the Lone Workers Policy in existence at the Cardiff HD
 Centre and will discuss visits with the research team prior to completing them to ensure
 that safety is not compromised at any time. Participants will be asked to complete the
 training programme provided using HAPPYneuron software for a minimum of 30 minutes 3
 times a week for 12 weeks. After the participant completes the 30 minute training
 programme they will be free to complete any other of the 'games' available on the
 HAPPYneuron computerised cognitive training software. Completion of the cognitive
 training programme will be monitored and supported using email or telephone reminders
 (as preferred by the participant) and home visits by the researcher. This will allow
 patient adherence with the cognitive intervention programme to be monitored and
 therefore the feasibility and acceptability of the programme by the participant to be
 explored. Each participant will be provided with a unique log in. The software provides
 an interface that allows the researcher to track the regularity of use and progress of
 all study participants. Therefore, the investigators will be able to remotely determine
 how often and for how long participants are using the software and can analyse
 participant performance on each cognitive task. Furthermore, the performance of
 participants for each specific task, during each cognitive training session is measured
 and can be used to determine improvements in specific cognitive tasks, for example in
 response accuracy or response time, throughout the study. Participants will be made
 aware that the researcher is able to see their training activity throughout the study.

 The cognitive training software the investigators plan to use in this study is easy to
 use, is automated, provides non-biased data recording, provides an interface which
 allows the researcher to track compliance remotely. It has previously been validated in
 both healthy controls and patients with depression, and has shown patient benefit
 including improved cognition and functionality. At the end of the study the participant
 login details will expire and they will no longer be able to access the cognitive
 training software, this is made clear in the PIS. The intervention is designed to be
 completed independently, although in this feasibility study, with the agreement of the
 participant, the investigators will be specifically exploring the involvement of any
 friends, family members of carers using semi-structured interviews at the beginning and
 end of the study.

 6.2. Magnetic Resonance Imaging (MRI) Scanning Cardiff University has a world leading
 brain imaging research centre (CUBRIC) which provides access to state of the art
 research facilities and equipment. Therefore, MRI scanning will be used in this study,
 as an optional component, to greater explore the biological effects if any, that the
 cognitive training programme may have. Prior to consent, potential participants will be
 screened for any contradictions to MRI. Further screening will be conducted prior to any
 MRI scanning procedures. MRI scanning is an optional component of the feasibility study,
 therefore if participants cannot or do not want to undergo the MRI scanning procedures,
 they will still be able to take part in the study. Participants will also be made aware
 that they are free to withdraw from the MRI scanning component of the study at any time,
 without the need to give a reason and this will not affect the care that they receive.

 If a participant consents to MRI, the MRI scanning procedure will be carefully explained
 and discussed with the participant and the participant will have the opportunity to
 experience the 'mock' MRI scanner, if they feel this may be helpful. The MRI scan will
 be conducted at a research visit 6 weeks into the intervention. An MRI scan will then be
 conducted by a fully trained MR Operator with the help of a researcher who is MR safety
 trained. The scan will be acquired on a 3T Siemens Prisma scanner with 32 head coils.
 The MRI scanning protocol will include scans to assess a structural scan to assess gross
 macrostructure, microstructural scans to assess white matter and myelination changes as
 well as quantitative fMRI to measure resting cerebral blood flow. The complete scanning
 protocol is expected to last no longer than 90 minutes, but will be led by the
 participant to ensure that they are comfortable throughout the scanning procedure.

 7. Data Collection For the majority of assessment procedures, data will be collected on
 paper data collection forms and the results of the tests subsequently transferred to a
 secure online database. The data in the online database will be verified against the
 paper form to ensure data integrity. Original data collection sheets will be filed and
 stored securely in the TMF.

 For the semi-structured interviews, questions will be asked orally by the researcher,
 audio recorded and transcribed verbatim. Although some flexibility may be necessary to
 avoid the need for protocol amendments. A list of topics to be included in the interview
 schedule for participants and family members, friends or carers who attend the research
 visit with the participant include:

 -  How the intervention is perceived/was received?

 -  Expected or perceived impact on daily routine

 -  Expected or perceived impact on family members/ carers

 -  Overall expectations

 -  Expected or perceived acceptability (support or help required)

 -  Thoughts and views on the randomisation procedure

 -  Potential barriers to completing the intervention

 -  General views or comments on the cognitive training intervention

 8. Data Analysis As the proposed study is a feasibility study for the use of computerised
 cognitive training for people with HD, the study is not formally powered. The primary
 aim is that of feasibility, so eligibility, recruitment and acceptability of the study
 will all be evaluated. Adherence to the proposed cognitive training intervention and any
 adverse effects will also be reported. Therefore, crucial inferences will be made which
 will allow an estimation of parameters that can inform definitive and future trials in
 this specific patient population.

 8.1. Statistical Analyses Summary statistics of demographics (age, gender, height and
 weight) and disease burden scores will be reported. Descriptive data will include an
 evaluation of eligibility, recruitment, retention rates and acceptability of, and
 adherence to the intervention, with 95% confidence intervals. The completion of outcome
 measures and assessments will also be reported. Graphical illustration will be used to
 check distributions of outcome data.

 Successful adherence to the intervention will be defined as having completed 12 weeks of
 the computerised cognitive training for a minimum of 3, 30 minute sessions per week.
 This is a feasibility study; thus an estimation of retention rates may be difficult with
 such as small sample size. Therefore, it is suggested that if retention rates are
 greater than 75%, the investigators will consider this intervention to be feasible. If
 the proportion retained is less than this but greater than 65%, the investigators will
 consider adjusting the intervention to increase this in future investigations. The
 qualitative work will help to establish why retention rates are as they are at the end
 of the study. A retention rate lower than this would require substantial changes to the
 intervention and therefore would require further piloting and feasibility studies.
 Changes in the outcome assessments in will be analyzed using analysis of covariance
 (ANCOVA) with the baseline score of that variable in addition to the balancing variables
 (age and UHDRS TMS) as covariates.

 Data collection will be performed via HAPPYneuron software systems and initially on data
 collection forms before transfer to a database. Data completeness will be monitored at
 the point of collection; therefore, the investigators do not expect large amounts of
 missing data. As it is our intention to inform future confirmatory trials, the
 investigators will explore the feasibility of outcomes as applied in this trial and this
 population. The investigators will consider internal reliability of all outcome
 measures, as some have not been previously used in HD or applied to computerised
 cognitive training interventions.

 9. Dissemination The research team are committed to disseminating the research findings to
 the general public and patient groups and will seek to present the results at patient
 open days, engagement events and outreach activities. Dissemination is a particular
 passion of the CI. Furthermore, in order to communicate the research widely, the results
 may be disseminated via social media, through newsletters and other patient engagement
 outlets in appropriate language and format for the general public to understand. If a
 participant indicates that they would like to be informed of the results of the trial a
 report of the findings will be sent to them at trial closure. Where results are
 presented, they will always be presented in such a way that data from individual
 participants cannot be identified. In addition to the significant public and patient
 outreach dissemination, the research findings will be written up for publication in a
 scientific journal. The results may also be presented at scientific meetings, or in
 talks at academic institutions.

 10. Data Storage, Handling, Retention and Confidentiality All data will be stored within a
 firewall and password-protected computer system within a swipe-card secured building.
 Researchers associated with the study will have confidential access to files, which
 allow the matching of recorded data to participants. No data, whether paper or
 electronic, will leave Cardiff University sites without being completely anonymised,
 i.e., all identifiable data will be removed from the dataset. Any electronic files or
 disks will be stored on Cardiff University sites and electronically on Cardiff
 University systems. At the conclusion of the study identifiable data will be destroyed
 and non-identifiable data will be archived, although it will still be accessible to the
 study team. Data will be archived for 15 years, in line with Cardiff University policies
 and procedures. Study data may be shared with the organisation funding the study. Where
 data leaves Cardiff University it will be strictly anonymised. Anonymised data may be
 shared with researchers at other organisations in the UK or overseas and it may be made
 publicly available for future research use. In the case of the data generated using
 HAPPYneuron systems, this data is captured centrally and stored outside of the Cardiff
 University systems and is therefore subject to HAPPYneuron's policies and procedures.
 However, a subset of this data will be extracted for use in the study and transferred on
 to Cardiff University systems as described above.

 All participant identification and referral procedures as well as procedures for data
 storage, processing and management will comply with the Data Protection Act 1998. Data
 will be kept for 15 years in line with Cardiff University's Research Governance
 Framework Regulations for clinical research. This data will be stored confidentially on
 password protected servers maintained on the Cardiff University Network. Data will be
 stored in locked cabinets and/or on secured computer hard-drives (password protected) in
 an access controlled building and will be retained indefinitely. This is in compliance
 with the guidelines set by the Cardiff University Research Governance Framework. The
 confidentiality of participants will be preserved in accordance with the Data Protection
 Act 1998. All participants will be allocated an Enroll-HD unique study number identifier
 and in the case of family members, friends or carers, they will be allocated a unique
 study number in relation to the participant. All data collected will be held in a linked
 anonymised form.

 11. Study Closure Definition The end of study is the date of the last visit of the last
 research participant.

 12. Indemnity Cardiff University will provide indemnity and compensation in the event of a
 claim by, or on behalf of participants, for negligent harm as a result of the study
 design and/or in respect of the protocol authors/research team. Cardiff University does
 not provide compensation for non-negligent harm.

 13. Sponsorship Cardiff University will act as sponsor for this study.

 14. Funding

 The study is funded by two research grants:

 1. 18 month research grant from the Jacque and Gloria Gossweiler Foundation, awarded to Dr.
 Emma Yhnell (Lead Applicant), Prof. Anne Rosser, Prof. Monica Busse and Dr. Claudia
 Metzler-Baddeley. 'Exploring cognitive training as a non-pharmaceutical therapeutic
 intervention for people with Huntington's disease.' (funding start date: 1st April 2016,
 study end date: 30th September 2017).

 2. 36 month fellowship award to Dr. Emma Yhnell from Health and Care Research Wales. 'Using
 computer based cognitive training to provide a personalised therapeutic intervention for
 people with Huntington's disease.' (funding start date: 1st October 2016, study end
 date: 30th September 2019).

 15. Study Management The project will be managed by the CI Dr. Emma Yhnell, with the support
 of colleagues from the Cardiff HD Centre, including Ms. Hannah Furby, Prof. Monica Busse
 (SEWTU), Prof. Anne Rosser (Clinical Responsible for Care) and Dr. Claudia Metzler-Baddeley
 (CUBRIC). In addition the CI will receive advisory support from members of SEWTU, in the form
 of monthly research meetings and email support for the duration of the project. The SEWTU
 advisory board includes: Dr Rachel Breen, Dr. Rebecca Playle, Mr. Gareth Watson and Dr. Lucy
 Brookes-Howells.
Inclusion Criteria:

 -  Confirmed HD diagnosis by genetic test.

 -  Over 18 years of age.

 -  Enrolled in the EHDN Registry/Enroll-HD study.

 -  Stable medication regime 4 weeks prior to recruitment (and not anticipated to change
 medications during the study period).

 Exclusion Criteria:

 -  Inability to provide consent.

 -  Any known neurological condition (other than HD).

 -  Currently actively involved in any other interventional trial (i.e. have begun the
 intervention) or within four weeks of completing the final assessments of an
 interventional trial.

 -  Currently regularly completing computerised brain training programme.

 -  MRI contraindications (e.g. a pacemaker) as established using standard screening
 procedures (optional).