DISENTANGLING THE ROLE OF PARVALBUMIN-EXPRESSING INTERNEURONS IN STIMULUS-RESPONSE LEARNING AND COGNITIVE FLEXIBILITY

Habits enable animals to efficiently navigate their surroundings while tending to more cognitively demanding environmental factors. One mechanism underlying habit is known as stimulus-response (S-R) learning, which takes place in the dorsolateral striatum (DLS). However, there is limited knowledge regarding the complex striatal microcircuits involved in S-R learning and cognitive flexibility. Recently, attention has turned toward the GABAergic Parvalbumin-expressing (PV) interneurons that can modulate striatal outputs. Here, we utilized chemogenetic techniques and touchscreen cognitive assessments to analyze the influence of PV neurons on S-R learning in mice. When PV neurons were inhibited, during the acquisition of a S-R and cognitive flexibility cognitive assessment, there were no significant differences in the percent accuracy. Further exploratory analysis, however, revealed a significant difference in the male mice but not the female mice between the experimental groups for the acquisition of the S-R task. Furthermore, PV neuron inhibition did not affect performance of a previously acquired S-R task. These findings contribute to our understanding of what mechanisms are and are not necessary for the various cognitive functions in which the dorsal striatum is involved

Adapting individual Cognitive Stimulation Therapy (iCST) for delivery by a touch-screen application for people with dementia

Introduction: people with dementia may benefit from technology to enhance their quality of life (QoL), reduce social isolation and potentially improve cognition. Adapting existing interventions to digital platforms is a promising approach with prospective benefits. Group Cognitive Stimulation Therapy (CST) for people with dementia can benefit cognition and QoL. Individual CST (iCST) is delivered by a carer at home and can improve the relationship quality between the person with dementia and carer, and the QoL of carers. Given the lack of technological resources for the mental stimulation and engagement of people with dementia, there are potential benefits of combining iCST with touch-screen technology, which include improving global accessibility to iCST. Aims: to develop and evaluate a touch-screen version of iCST, and examine its potential for implementation internationally. Methods: this study employed a mixed methods approach to the development and evaluation of a novel iCST app. Development included a narrative synthesis systematic review supported by the Medical Research Council (MRC) Framework and the Centre for eHealth Research (CeHRes) roadmap, and following principles of action research and the agile approach to software development. Forty-one people with dementia and carers were involved in patient and public involvement (PPI) consultation meetings, focus groups, individual interviews, and usability questionnaires. Evaluation included a two-arm, feasibility randomised controlled trial (RCT) (n = 43) to investigate the usability of the iCST app, and feasibility of conducting a large-scale RCT. Three dyads participated in semi-structured, post- trial interviews. Feasibility of cultural adaptation and implementation internationally was investigated in Indonesia where 39 people with dementia, carers, and healthcare professionals participated in focus groups and a stakeholder meeting. Results: the systematic review led to best practice guidelines on how to optimise involvement of people with dementia in technology development. These guidelines informed the development of the iCST app through three iterative prototypes. The idea of an iCST app was well received in PPI consultation meetings, and feedback indicated that the design and navigation of the prototypes were appropriate. A need for a wider range of more relevant activities was identified in the focus groups and interviews. The third prototype of the iCST app was used for the feasibility RCT. Carers using the iCST app rated their QoL better at follow-up 2 (FU2) compared to the treatment as usual (TAU) control group (EQ-5D, MD = 6.34, 95% CI = .92 – 11.76, p = .02). No other significant differences were found. The exploratory work in Indonesia indicated that it is feasible to implement the iCST app given appropriate cultural adaptation and provided that logistical barriers to accessibility have been overcome. Conclusions: this is the first study to develop and evaluate an interactive, touch- screen version of iCST. Findings indicate certain modifications to the trial components including increased recruitment capacity and sample size, and an augmented version of the iCST app. Expansion of the iCST app is needed as most participants completed the activities more quickly than anticipated and therefore, did not receive the recommended dose. Given these adaptations to the study design, it is recommended to conduct a large-scale RCT to investigate formal effectiveness

Adapting individual Cognitive Stimulation Therapy (iCST) for delivery by a touch-screen application for people with dementia

Introduction: people with dementia may benefit from technology to enhance their quality of life (QoL), reduce social isolation and potentially improve cognition. Adapting existing interventions to digital platforms is a promising approach with prospective benefits. Group Cognitive Stimulation Therapy (CST) for people with dementia can benefit cognition and QoL. Individual CST (iCST) is delivered by a carer at home and can improve the relationship quality between the person with dementia and carer, and the QoL of carers. Given the lack of technological resources for the mental stimulation and engagement of people with dementia, there are potential benefits of combining iCST with touch-screen technology, which include improving global accessibility to iCST. Aims: to develop and evaluate a touch-screen version of iCST, and examine its potential for implementation internationally. Methods: this study employed a mixed methods approach to the development and evaluation of a novel iCST app. Development included a narrative synthesis systematic review supported by the Medical Research Council (MRC) Framework and the Centre for eHealth Research (CeHRes) roadmap, and following principles of action research and the agile approach to software development. Forty-one people with dementia and carers were involved in patient and public involvement (PPI) consultation meetings, focus groups, individual interviews, and usability questionnaires. Evaluation included a two-arm, feasibility randomised controlled trial (RCT) (n = 43) to investigate the usability of the iCST app, and feasibility of conducting a large-scale RCT. Three dyads participated in semi-structured, post- trial interviews. Feasibility of cultural adaptation and implementation internationally was investigated in Indonesia where 39 people with dementia, carers, and healthcare professionals participated in focus groups and a stakeholder meeting. Results: the systematic review led to best practice guidelines on how to optimise involvement of people with dementia in technology development. These guidelines informed the development of the iCST app through three iterative prototypes. The idea of an iCST app was well received in PPI consultation meetings, and feedback indicated that the design and navigation of the prototypes were appropriate. A need for a wider range of more relevant activities was identified in the focus groups and interviews. The third prototype of the iCST app was used for the feasibility RCT. Carers using the iCST app rated their QoL better at follow-up 2 (FU2) compared to the treatment as usual (TAU) control group (EQ-5D, MD = 6.34, 95% CI = .92 – 11.76, p = .02). No other significant differences were found. The exploratory work in Indonesia indicated that it is feasible to implement the iCST app given appropriate cultural adaptation and provided that logistical barriers to accessibility have been overcome. Conclusions: this is the first study to develop and evaluate an interactive, touch- screen version of iCST. Findings indicate certain modifications to the trial components including increased recruitment capacity and sample size, and an augmented version of the iCST app. Expansion of the iCST app is needed as most participants completed the activities more quickly than anticipated and therefore, did not receive the recommended dose. Given these adaptations to the study design, it is recommended to conduct a large-scale RCT to investigate formal effectiveness

Involvement of People With Dementia in the Development of Technology-Based Interventions: Narrative Synthesis Review and Best Practice Guidelines

Background: Technology can be helpful in supporting people with dementia in their daily lives. However, people with dementia are often not fully involved in the development process of new technology. This lack of involvement of people with dementia in developing technology-based interventions can lead to the implementation of faulty and less suitable technology.Objective: This systematic review aims to evaluate current approaches and create best practice guidelines for involving people with dementia in developing technology-based interventions.Methods: A systematic search was conducted in January 2019 in the following databases: EMBASE (Excerpta Medica database), PsycINFO, MEDLINE (Medical Literature Analysis and Retrieval System Online), CINAHL (Cumulated Index to Nursing and Allied Health Literature), and Web of Science. The search strategy included search terms in 3 categories: dementia, technology, and involvement in development. Narrative synthesis wove the evidence together in a structured approach.Results: A total of 21 studies met the inclusion criteria. Most studies involved people with dementia in a single phase, such as development (n=10), feasibility and piloting (n=7), or evaluation (n=1). Only 3 studies described involvement in multiple phases. Frequently used methods for assessing involvement included focus groups, interviews, observations, and user tests.Conclusions: Most studies concluded that it was both necessary and feasible to involve people with dementia, which can be optimized by having the right prerequisites in place, ensuring that technology meets standards of reliability and stability, and providing a positive research experience for participants. Best practice guidelines for the involvement of people with dementia in developing technology-based interventions are described

An Individual Cognitive Stimulation Therapy App for People With Dementia and Their Carers: Protocol for a Feasibility Randomized Controlled Trial

Background:There is a need for more resources to support the cognition and quality of life (QoL) of people with dementia. The individual Cognitive Stimulation Therapy application (iCST app) aims to provide cognitive stimulation and social interaction to people with dementia and carers through interactive touch-screen technology. It has been developed according to the principles of CST and iCST which have previously shown to improve the cognition and QoL of people with dementia, and to benefit the relationship between the person with dementia and carer, while improving quality of the carer’s life. This study aims to evaluate the feasibility of conducting a full-scale, randomized controlled trial (RCT) with the iCST app.Objective:To evaluate the feasibility of conducting a full-scale RCT with the iCST app compared to a treatment as usual (TAU) control group.Methods:A multi-centre, pragmatic, single blind, feasibility RCT with a treatment as usual (TAU) control group. This study aims to recruit 60 people with mild to moderate dementia and their informal carers as dyads. Both parties must be able to provide informed consent and participate in the intervention. Dyads will complete a baseline assessment which will include cognition and QoL measures, and will subsequently be randomized (1:1) to the iCST app intervention in addition to usual care, or to usual care only. All participants will be followed-up at 5 weeks and 11 weeks post-baseline. A range of feasibility outcomes will be assessed including recruitment and retention rates, intervention fidelity and usability, and acceptability of the outcome measures. A sample of the experimental group will be invited to a semi-structured post-trial interview to further examine the experience of using the iCST app.Results:Recruitment began in November 2018 with 43 dyads recruited from primary and secondary care settings. Participants were randomized to the iCST app (n = 21) or TAU control group (n = 22) with a relatively low attrition rate throughout the study (n = 2). Dementia support groups and (online) research databases led to the majority of the referrals for the study.Conclusions:This study will investigate whether it is feasible to conduct a full-scale RCT to evaluate the clinical effectiveness of the iCST app in comparison to usual care alone. In addition, it will further examine the usability of the iCST app. The data will provide information on potential modifications to be made to the intervention, study design, and study process. Clinical Trial: ClinicalTrials.gov, NCT03282877. Registered on 19 July 2017

An Individual Cognitive Stimulation Therapy App for People With Dementia and Their Carers: Protocol for a Feasibility Randomized Controlled Trial

Background:There is a need for more resources to support the cognition and quality of life (QoL) of people with dementia. The individual Cognitive Stimulation Therapy application (iCST app) aims to provide cognitive stimulation and social interaction to people with dementia and carers through interactive touch-screen technology. It has been developed according to the principles of CST and iCST which have previously shown to improve the cognition and QoL of people with dementia, and to benefit the relationship between the person with dementia and carer, while improving quality of the carer’s life. This study aims to evaluate the feasibility of conducting a full-scale, randomized controlled trial (RCT) with the iCST app.Objective:To evaluate the feasibility of conducting a full-scale RCT with the iCST app compared to a treatment as usual (TAU) control group.Methods:A multi-centre, pragmatic, single blind, feasibility RCT with a treatment as usual (TAU) control group. This study aims to recruit 60 people with mild to moderate dementia and their informal carers as dyads. Both parties must be able to provide informed consent and participate in the intervention. Dyads will complete a baseline assessment which will include cognition and QoL measures, and will subsequently be randomized (1:1) to the iCST app intervention in addition to usual care, or to usual care only. All participants will be followed-up at 5 weeks and 11 weeks post-baseline. A range of feasibility outcomes will be assessed including recruitment and retention rates, intervention fidelity and usability, and acceptability of the outcome measures. A sample of the experimental group will be invited to a semi-structured post-trial interview to further examine the experience of using the iCST app.Results:Recruitment began in November 2018 with 43 dyads recruited from primary and secondary care settings. Participants were randomized to the iCST app (n = 21) or TAU control group (n = 22) with a relatively low attrition rate throughout the study (n = 2). Dementia support groups and (online) research databases led to the majority of the referrals for the study.Conclusions:This study will investigate whether it is feasible to conduct a full-scale RCT to evaluate the clinical effectiveness of the iCST app in comparison to usual care alone. In addition, it will further examine the usability of the iCST app. The data will provide information on potential modifications to be made to the intervention, study design, and study process. Clinical Trial: ClinicalTrials.gov, NCT03282877. Registered on 19 July 2017

Field-testing an iCST touch-screen application with people with dementia and carers: a mixed method study

Objectives: To test the individual Cognitive Stimulation Therapy (iCST) application with people with dementia and carers in order to modify and refine the application, and improve its usability. In an iterative development process, two different prototypes were used to elicit the subjects’ views and preferences. This application may address the current need for more innovative approaches to support people with dementia and their carers.Methods: An opportunistic sample of 13 people with dementia and 13 carers participated in four focus groups and ten semi-structured interviews to obtain feedback in key areas, including the layout and content of the application, and the experience of its use as a dyad. Data were audio-recorded, transcribed and analysed thematically. An additional 18 people with dementia and 16 carers completed a short usability and acceptability questionnaire regarding a subsequent version of the iCST application prototype.Results: Most participants expressed enthusiasm about the iCST application, its usability, design, and content. Participants highlighted the importance of adaptability to individual preferences, indicating a need for a wider range of activities and flexibility in the use of the application. Furthermore, participants reported perceived benefits, including mental stimulation, quality time spent together, and enjoyment. The application was rated slightly better by carers than people with dementia in terms of usability and acceptability.Conclusions: This study gives insights from people with dementia and carers concerning the usability, feasibility, and perceived benefits of the iCST application. The feedback will be incorporated in an updated version of the iCST application for commercial release

Digital technologies to prevent social isolation and loneliness in dementia : a systematic review

Background: Dementia poses significant and sustained challenges to global society. Diagnosis can lead to increased feelings of loneliness and social isolation. People with dementia living alone are particularly at risk. Considering the growing number of technologies proposed to aid people with dementia address social isolation and loneliness, we reviewed the existing literature. Objective: To collate and summarize current evidence for digital technologies to prevent social isolation and loneliness for people with dementia. Methods: Following the PRISMA guidelines, we systematically searched five databases to identify studies of digital technologies designed to support or prevent social isolation or loneliness for people with dementia. Pre-specified outcomes included social isolation, loneliness, and quality of life. We used deductive thematic analysis to synthesize the major themes emerging from the studies. Results: Ten studies met our inclusion criteria where all studies reported improvements in quality of life and seven reported benefits regarding social inclusion or a reduction in loneliness. Technologies were varied across purpose, delivery format, theoretical models, and levels of personalization. Two studies clearly described the involvement of people with dementia in the study design and five technologies were available outside the research context. Conclusion: There is limited— but increasing— evidence that technologies hold potential to improve quality of life and reduce isolation/loneliness for people with dementia. Results presented are largely based in small-scale research studies. Involvement of people with dementia was limited and few research concepts are reaching implementation. Closer collaboration with people with dementia to provide affordable, inclusive, and person-centered solutions is urgently required