The use of Acceptance and Commitment Therapy to address psychological distress experienced by caregivers: a randomised controlled feasibility trial

Background: An extensive research literature has documented the impact of caring for an individual with acquired brain injury (ABI) on caregivers and family members, including role adjustment, psychological distress, social isolation, family tension and coping with the cognitive and behavioural difficulties of the injured person. Given these findings it is important this population have access to services and supports. Acceptance and Commitment Therapy (ACT) is an intervention that helps individuals to accept difficult experiences and commit to behaviour that is consistent with their values. Research into the effectiveness of ACT to support caregivers is at a preliminary stage. Aim: To investigate the feasibility of using ACT to reduce psychological distress and increase psychological flexibility in ABI caregivers. A secondary aim was to gain an understanding of the experience of caregivers in this context and how this can inform the development and delivery of interventions for this population. Method: Phase one was a randomised controlled feasibility trial of an ACT intervention for use with ABI caregivers. The parameters of this study were formulated around the PICO (population, intervention, control, and outcome) framework. Eighteen carers were recruited and randomised to ACT or an enhanced treatment as usual (ETAU) group. ACT was implemented over 3 sessions; and ETAU was implemented over 2 sessions. The General Health Questionnaire, Valuing Questionnaire, Acceptance and Action Questionnaire, Experiential Avoidance of Caregiving Questionnaire and the Flexibility of Responses to Self-Critical Thoughts Scale were administered to both groups at baseline and following the final session. Phase two used a retrospective qualitative design that involved conducting semi-structured interviews with four participants from phase one. Results: ACT and control participants were successfully recruited. Positive feedback was obtained from ACT participants suggesting that the intervention was acceptable. There were no significant differences between the ACT and ETAU groups on outcome measures. However, there were challenges retaining participants and the overall attrition rate was high (44.44%). Therefore a number of participants did not complete the full complement of sessions, which may have impacted on this result. Qualitative results illustrated the challenges this population face including significant adjustments in their life, the emotional impact of having a loved one with a brain injury and trying to adapt to the changes in the injured person. In addition, findings elucidated the types of support that this population would find helpful and the barriers to accessing same. Conclusions: Findings from this study highlight factors that will help the development of this intervention further for a caring population. Recommendations for future implementation include completing some preparatory work with carers before beginning the intervention, consideration of a larger sample and wider recruitment strategy from local services, barriers to attending interventions and the possibility of holding groups in local venues.

Investigating assistive technology to support memory for people with cognitive impairments

Technologies such as automobiles or mobile phones allow us to perform beyond our physical capabilities and travel faster or communicate over long distances. Technologies such as computers and calculators can also help us perform beyond our mental capabilities by storing and manipulating information that we would be unable to process or remember. In recent years there has been a growing interest in assistive technology for cognition (ATC) which can help people compensate for cognitive impairments. The aim of this thesis was to investigate ATC for memory to help people with memory difficulties which impacts independent functioning during everyday life. Chapter one argues that using both neuropsychological and human computing interaction theory and approaches is crucial when developing and researching ATC. Chapter two describes a systematic review and meta-analysis of studies which tested technology to aid memory for groups with ABI, stroke or degenerative disease. Good evidence was found supporting the efficacy of prompting devices which remind the user about a future intention at a set time. Chapter three looks at the prevalence of technologies and memory aids in current use by people with ABI and dementia and the factors that predicted this use. Pre-morbid use of technology, current use of non-tech aids and strategies and age (ABI group only) were the best predictors of this use. Based on the results, chapter four focuses on mobile phone based reminders for people with ABI. Focus groups were held with people with memory impairments after ABI and ABI caregivers (N=12) which discussed the barriers to uptake of mobile phone based reminding. Thematic analysis revealed six key themes that impact uptake of reminder apps; Perceived Need, Social Acceptability, Experience/Expectation, Desired Content and Functions, Cognitive Accessibility and Sensory/Motor Accessibility. The Perceived need theme described the difficulties with insight, motivation and memory which can prevent people from initially setting reminders on a smartphone. Chapter five investigates the efficacy and acceptability of unsolicited prompts (UPs) from a smartphone app (ForgetMeNot) to encourage people with ABI to set reminders. A single-case experimental design study evaluated use of the app over four weeks by three people with severe ABI living in a post-acute rehabilitation hospital. When six UPs were presented through the day from ForgetMeNot, daily reminder-setting and daily memory task completion increased compared to when using the app without the UPs. Chapter six investigates another barrier from chapter 4 – cognitive and sensory accessibility. A study is reported which shows that an app with ‘decision tree’ interface design (ApplTree) leads to more accurate reminder setting performance with no compromise of speed or independence (amount of guidance required) for people with ABI (n=14) compared to a calendar based interface. Chapter seven investigates the efficacy of a wearable reminding device (smartwatch) as a tool for delivering reminders set on a smartphone. Four community dwelling participants with memory difficulties following ABI were included in an ABA single case experimental design study. Three of the participants successfully used the smartwatch throughout the intervention weeks and these participants gave positive usability ratings. Two participants showed improved memory performance when using the smartwatch and all participants had marked decline in memory performance when the technology was removed. Chapter eight is a discussion which highlights the implications of these results for clinicians, researchers and designers.

FAM49 - A novel regulator of the protrusive behaviour and motility of cells

Most eukaryotic cell motility relies on plasma membrane protrusions, which depend on the actin cytoskeleton and its tight regulation. The SCAR/WAVE complex, a pentameric assembly comprising SCAR/WAVE, Nap1, CYFIP/Pir121, Abi and HSPC300, is a key driver of actin-based protrusions such as pseudopods. SCAR/WAVE is thought to activate the Arp2/3 complex, a crucial actin nucleator, after being itself activated by upstream signals such as active Rac1. Despite recent progress on the study of the SCAR/WAVE complex, its regulation is still incompletely understood, with Nap1’s role being particularly enigmatic. Upon screening for potential Nap1 binding partners in the social amoeba Dictyostelium discoideum – a well established model organism in the study of the actin cytoskeleton and cell motility – we found FAM49, a ~36 kDa protein of unknown function which is highly conserved in Metazoa (animals) and evolutionarily closer species such as D. discoideum. Interestingly, D. discoideum’s FAM49 and its homologs contain a DUF1394 domain, which is also predicted in CYFIP/Pir121 proteins and most likely involved in their direct binding to active Rac1, which in turn contributes to SCAR/WAVE’s activation. FAM49’s unknown role, apparent high degree of conservation and potential connections to SCAR/WAVE and Rac1 persuaded us to start investigating its function and biological relevance in D. discoideum, leading to the work presented in this thesis. Several pieces of our data collectively support a function for FAM49 in modulating the protrusive behaviour, and ultimately motility, of D. discoideum cells, as well as a regulatory link between FAM49 and Rac1. FAM49’s involvement in protrusion regulation was first hinted at by our observation that GFP-tagged FAM49 is enriched in pseudopods. The possibility of a link with Rac1 was then strengthened by two additional observations: first, pseudopodial GFP-FAM49 is substantially co-enriched with active Rac, both showing fairly comparable spatio-temporal accumulation dynamics; second, when dominant-active (G12V) Rac1 is expressed in cells, it triggers the recruitment and persistent accumulation of GFP-FAM49 at the plasma membrane, where both become highly co-enriched. We subsequently determined that fam49 KO cells differ from wild-type cells in the way they protrude and move, as assessed in under-agarose chemotaxis assays. In particular, our data indicate that fam49 KO cells tend to display a lower degree of global protrusive activity, their protrusions extend more slowly and are less discrete, and the cells end up moving at lower speeds and with higher directional persistence. This phenotype was substantially rescued by FAM49 re-expression. While re-expressing FAM49 in fam49 KO cells we generated putative FAM49 overexpressor cells; compared to wild-type cells, they displayed atypically thin pseudopods and what seemed to be an excessively dynamic, and perhaps less coordinated, protrusive behaviour. Additional data in our study suggest that pseudopods made by fam49 KO cells are still driven by SCAR/WAVE, which is clearly not being replaced by WASP (as is now known to be the case in D. discoideum cells lacking a functional SCAR/WAVE complex). Nonetheless, the peculiar dynamics of those pseudopods imply that SCAR/WAVE’s activity is regulated differently when FAM49 is lost, though it remains to be determined how. This thesis is the first report of a dedicated study on FAM49 and lays the foundation for future research on it.