Exploring Computerised Cognitive Training for People With Huntington's Disease

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.