The development and evaluation of exercise, cognitive, and dual-task interventions targeting cognitive dysfunction in type 2 diabetes mellitus

Approximately 3.5 million individuals are diagnosed with diabetes in the UK, with 90% of cases attributed to type 2 diabetes mellitus (T2DM). The worldwide prevalence of T2DM has rapidly increased, rising from 108 million in 1980 to 422 million in 2014. In addition to the well-recognised microvascular and macrovascular complications, emerging evidence suggests that T2DM is also associated with an increased risk of cognitive dysfunction. Considering the increasing prevalence, in addition to the increasing life expectancy of older adults, the development of cognitive dysfunction in this population may seriously challenge future health services. Therefore, there is an urgent need to identify effective strategies that may lead to improved therapy in the future. Whilst exercise, cognitive, and dual-task interventions have previously been identified as successful strategies for targeting cognition in other population groups, little is known regarding the effect of these types of interventions in T2DM. The primary aim of this doctoral thesis was to develop and evaluate exercise, cognitive, and dual-task interventions for targeting cognitive dysfunction in individuals with T2DM. The series of studies presented in this thesis (chapters 2-5) were conducted using a systematic phased approach in accordance with the MRC’s framework for the development and evaluation of complex interventions. The initial study (chapter 2) involved conducting a systematic review and meta-analysis and identified only a limited number of exercise, cognitive, and dual-task trials in T2DM. The overall quality of included trials was mixed, with the majority of trials having a moderate to high risk of bias. Meta-analyses of exercise trials showed small to moderate effects of exercise on executive function (0.31) and memory (0.20), but were not statistically significant. Due to the limited number of cognitive and dual-task trials identified, a narrative synthesis was conducted which showed a positive effect of these types of interventions for improving tasks of global cognition, executive function and memory. It was concluded that larger, more robust trials were needed to further understand the impact of these types of intervention in T2DM. The subsequent study (chapter 3) piloted exercise, cognitive, and dual-task interventions in T2DM to help identify a suitable intervention to test for feasibility and acceptability. The findings of this intervention development study found cognitive training was the most iv enjoyable and preferred. Together, the accumulated evidence identified in study 1 and 2 was used to develop a suitable cognitive training study ready to be evaluated for its feasibility and acceptability in T2DM. The final study as part of this doctoral thesis aimed to explore the feasibility (chapter 4) and acceptability (chapter 5) of a cognitive training study in T2DM. Feasibility was shown in important aspects of the study including the adherence, retention and motivation of participants whilst only minor amendments were recommended to the study design, recruitment pathways, and data collection. Improvements in several cognitive domains including executive function, visual memory, and reaction time were also observed following cognitive training in which serum levels of BDNF were shown to unexpectedly reduce following cognitive training. The acceptability findings suggest that participants found the cognitive training study highly enjoyable and that the study components were well accepted in this population. However, recommendations were made for clearer communication of the study aims and processes in addition to greater involvement for those allotted to the control group. Evidence derived from both the quantitative (chapter 4) and qualitative (chapter 5) elements of this study were used to develop a set of important recommendations that should be considered prior to undertaking a future definitive trial. Overall, the findings from this doctoral thesis provide systematic and convincing evidence for the potential feasibility, acceptability, and efficacy of a randomised controlled trial to evaluate the effectiveness of a cognitive training intervention in T2DM