NIHRDataInsights/HRCSData huggingface dataset:
Title: Informant assessments for diagnosis of dementia – an overview review
Funder: Department of Health and Social Care

Abstract: We plan an overview review describing test accuracy of informant based cognitive screening. Choice of topic is based on the following factors: Policy importance: Dementia is a growing public health concern, by 2025 more than one million people in the UK will have dementia. Robust diagnosis is a crucial first step in management and recent government policy has emphasised the need for early diagnosis. However, there is no agreement on the optimal approach to assessment. National Institute for Health and Care Excellence (NICE) are updating guidance on cognitive assessment and are keen to see an overview review of the evidence (personal communications with Cochrane Dementia). Patient and carer importance: Consultation with people whose lives are affected by dementia, for example the recent James Lind Alliance Priority Setting Partnership, has highlighted the importance placed on diagnosis. In our own work, recurring themes have been the need for minimising test burden and including family and carers. Informant based assessments meet these criteria. Cochrane importance: Cochrane Dementia are keen to develop expertise in overview review methods. We have performed initial scoping and our chosen topic has sufficient reviews (around 10) to justify an overview but can still be delivered in the required timeframe.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Cognitive training for people with dementia
Funder: Department of Health and Social Care

Abstract: Across the UK, ever increasing numbers of older adults with mild dementia urgently need interventions that may improve their cognitive and functional abilities, or at least slow down their cognitive/functional decline. Cognitive training (CT) is a non-pharmacological approach targeting specific cognitive processes through repeated practice on standardised cognitive tasks. Interest in CT across the lifespan, including in older adults with and without cognitive impairment, has grown exponentially in recent years, with numerous publications on the topic appearing every year. To date, reviews on the efficacy of CT for persons with dementia have yielded mixed findings, and a booming commercial industry has emerged, an industry which at times exploits the uncertainty in the field by making ethically-questionable claims regarding therapeutic values of their products. Whereas there is some evidence of therapeutic benefits associated with CT among older adults who are cognitively healthy or who show mild cognitive impairment, previous versions of this Cochrane review failed to find evidence of meaningful benefit for people with mild dementia. Due to the accelerating rate of trial publications in this area, there is a pressing need for an update of this review, which is now expected to yield firmer conclusions.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: NEUROLOGICAL
Title: Parent-mediated communication interventions for improving the communication skills of preschool children with non-progressive motor disorders
Funder: Department of Health and Social Care

Abstract: Cerebral palsy affects 2-3/1000 live births. Approximately half of all children with the condition have a communication difficulty. The number of children with other non-progressive motor disorders is unknown. Services provide wide ranging models of provision that vary in: personnel, format (individual/group), duration, frequency, method of training and content. The review will provide evidence on dosage of effective interventions and treatment mechanisms, and could identify specific programmes/active ingredients to be included in local service delivery. The review will inform provision according to the Special Educational Needs and Disability Code of Practice (England), which highlights communication as a key learning outcome in early years. Also, by including all children with non-progressive motor disorders, the review will extend the NICE Cerebral Palsy 0-25 Guideline, which recommended that all children with cerebral palsy who have communication difficulties be provided with parent training. Parents and clinicians designated communication development and evaluation of intervention effectiveness as the top two priorities in a James Lind Alliance priority setting exercise (Morris et al 2015). Carers are not involved in reviewing of evidence, but will be consulted about the findings of the study, via PENCRU (www.pencru.org/evidence) and parent-carer forums. Findings will be disseminated in summaries for lay readers.


Research activity codes: 6.7 PHYSICAL
Health categories: NEUROLOGICAL
Title: Genome Medicine and Bioinformatics (GMB)
Funder: Department of Health and Social Care

Abstract: Aims: Genome variants have the potential to inform each theme on the basis, likelihood of onset, and response to treatment for a disease endophenotype. Using genomic stratification, molecular models and biomarkers, we will employ a personalised medicine approach to deliver patient stratification, target prioritisation, drug repurposing and prediction of outcome. It uses genomic variants in the context of clinical outcome, phenotypic and experimental data. Shifting the focus in neurological diseases from the contribution of individual genes and pathways to a systems approach. Short term (1-2 years): 1. Train a cadre of quantitatively competent neuroscience researchers. 2. Provide support for bioinformatics analyses and data management. 3. Provide an integrative commons for deposition, workflow analysis and sharing of datasets ensuring reproducible experimental data. 4. Identify the complex of molecular signatures able to provide integrative, empirical, longitudinal predictive readouts of disease progression in motor neuron disease (MND), Alzheimer's disease and dementia. 5. Establish and support in silico drug screening across themes. Medium term: 1. Provide an accredited pathway from introductory to advanced training for quantitative analytics in neuroscience by integration of the existing Genomic Medicine MSc and graduate training. 2. Integrate genomics with enhanced measures of phenotype, experimental and clinical data to expose distinct processes that contribute to individual risk of disease, and validate these as predictive models. 3. Deliver personalised genomics influenced interpretation of neurological diseases in the context of experimental medicine performed in each subtheme. Long term: 1. Establish integrated genomic disease prediction and surveillance to deliver preventive interventions,targets and repurposed drugs tailored for patient genomic and clinical-phenotypic context.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: NEUROLOGICAL
Title: Advanced Medical Imaging
Funder: Department of Health and Social Care

Abstract: Short (1-2 years): 1. Further develop/implement MR sub-modality techniques, acquisition protocols and analysis tools, including: a. Multinuclear spectroscopy (including 31P, 22Na). b. 1H spectral editing (mainly to indicate GABA / Glx inhibitory / excitatory balance). c. Endogenous perfusion, macrovascular flow, advanced diffusion, fMRI & resting-state fMRI. d. Multi-contrast carotid plaque characterisation. 2. Initiate in-vivo acquisition in specific neuroscience sub-theme projects. 3. Investigate semi-automated muscle volumetry based on whole-body imaging (denervation studies) & integrate with biomechanical neuromotor assessments. 4. Initial evaluation of quantitative imaging of both cardiac output and brain vascular function using a multi-organ concurrent MRI strategy. 5. Procurement, commissioning and initial project design (with an initial emphasis on neurodegenerative applications) of a state-of-the-art PET-MRI system. Medium (3-4 years): 1. Multi-modal technique integration on the installed PET-MRI system. 2. Investigate changes in muscle composition (fat heterogeneity, texture) associated with degeneration. 3. Initiate longitudinal data acquisition (where appropriate). 4. Develop hyperpolarised brain tracers (129Xe), compare 1H exogenous / endogenous perfusion assessments & link these with Xe findings. Long term (5+ years): 1. Concurrent PET-MRI, multinuclear and hyperpolarised data acquisitions in multiple organ systems linked to the CNS as well as the CNS itself. 2. Develop radiochemistry to extend further short-lived isotope and novel ligand radionuclide tracer capability (eg. markers for microglial inflammatory component of neurodegeneration). 3. Bring together multi-dimensional imaging research space analysis to yield a transformable metric or set of summary metrics that will act as realistic, practical markers necessary for efficient future translational experimental medicine studies.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: NEUROLOGICAL
Title: Dementia and Related Disorders
Funder: Department of Health and Social Care

Abstract: Aims 1. Expand our patient and public involvement (PPI) infrastructure. 2. Build on our achievements as Europe’s leading clinical trial centre for dementia to deliver our ambitious therapeutics programme. 3. Expand opportunities for online intervention studies to maintain cognitive health and prevent cognitive decline through our PROTECT platform of 20,000 older adults. 4. Deliver innovative and novel intervention studies of a biological therapy. 5. Use our Care Home Research Network to launch new intervention studies focusing on treating priority mental health symptoms and pain in people with dementia. 6. Innovative development of clinical trials embedded within our clinical record system using our Clinical Record Interactive Search (CRIS). 7. Use opportunities related to polygenic risk, candidate genes and specific risk factors to launch precision medicine RCTs. 8. Deliver improved biomarker outcomes for clinical trials in Alzheimer’s disease and dementia with Lewy bodies. Objectives Short term  Complete stem cell trial in Alzheimer’s disease  Expand our PPI programme to reach wider (especially under-represented) populations Commence:  Three adaptive clinical trial platforms  One new online RCT through PROTECT  Two RCTs of mental health symptoms in dementia  Cluster RCT within CRIS Medium term  Improved biomarkers for trials  Introduce social media to our PPI work Commence:  Two precision RCTs  Two new trials for mental health symptoms  Two interventions in each adaptive trial platform  Second RCT within CRIS Long term Complete:  Trials within adaptive platform  Second wave of mental health RCTs  Second RCT through CRIS  Two further precision RCTs


Research activity codes: 3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: NEUROLOGICAL
Title: Development and Implementation of Neuroimaging Analysis in Dementia
Funder: Health Education England

Abstract: The NHS annually spends £50-100M on brain scanning but recognising the signs of dementia in scans is difficult. Comparing patient scans to images of healthy volunteers using analysis software is helpful and has been shown to improve the accuracy of diagnosis. However this technique is not routinely used as it is complicated and difficult to ensure it is producing accurate results. Therefore we have developed new devices to calibrate brain scanners so that the analysis software is more accurate. We will also provide training in the use of the software to clinicians using imaging case studies.

Lay abstract: The NHS annually spends £50-100M on brain scanning but recognising the signs of dementia in scans is difficult. Comparing patient scans to images of healthy volunteers using analysis software is helpful and has been shown to improve the accuracy of diagnosis. However this technique is not routinely used as it is complicated and difficult to ensure it is producing accurate results. Therefore we have developed new devices to calibrate brain scanners so that the analysis software is more accurate. We will also provide training in the use of the software to clinicians using imaging case studies.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: A feasibility study of facilitated reminiscence for people with dementia
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: The aim of this feasibility study is to investigate the effects of individual specific reminiscence, facilitated through the use of bespoke software, on people with dementia and their carers. The objectives are 1) to refine the software specification (MemoryLane) and its application to tablet devices, 2) to test the usability of the system, 3) to examine the impact of facilitated reminiscence on people with dementia and their carers, 4) to explore users’ views on MemoryLane, 5) to promote independence and quality of life and 6) to incorporate an economic analysis with a view to informing a full cost-effectiveness study alongside a future RCT. The research will be conducted in the homes of participants within the Western Health and Social Care Trust and will have quantitative and qualitative components in three phases. Phase 1: A User Development Group consisting of Graeme Skelton (Co-Investigator) and a paired sample of 6 additional people with dementia and their carers, will work with the research team to co-create and test an updated MemoryLane system. Phase 2: The refined application will be implemented with a paired sample of 30 people with dementia and their family carers. A reminiscence trainer from the Reminiscence Network Northern Ireland will guide participants in the collection of memorabilia. Then an IT assistant will provide training in the use of MemoryLane. Participants will use the system for 4 months. Data on the usability of MemoryLane and its impact will be collected from all participants pre-implementation and at four time points post implementation. Outcome measures will examine the impact of reminiscence on mutuality, wellbeing, quality of life and quality of the relationship between the person with dementia and their carer. Phase 3: Individual interviews will be conducted with people with dementia and their carers to explore their experience of MemoryLane.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: 2014 Dementia Care - Technology enriched supported housing - a study into the lived experience of elders with dementia and their carers
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: As people age it is not uncommon for dementia to develop. When this happens, over time, people may forget how to do everyday things to both look after themselves and keep safe. Eventually it may be risky for the person with dementia to continue to live alone, or even when they live with a spouse sometimes the demands of caring become too much. Daughters and sons who are caring for their relative from their own family base can feel very worried and stressed about how vulnerable they consider there loved one to be. When living at home is no longer an option then alternatives should be available. Supported housing is one such alternative, bringing together best design of housing and care offering a real home like alternative to hospital care. Some supported housing now use technology, with sensors in the flats to let staff know how people are managing within their own place. Some schemes like this have been in existence in Northern Ireland for over 10 years, supporting people with dementia and their families. In this study we plan to explore these schemes, to find out what it is like living in such a place and what families and care workers think about these types of living options. The aim is to help us understand the good things about these types of schemes, what can be improved and what we need to change. Once we figure this out we want to share what we find with all those people who are interested in using, developing and monitoring these facilities – establishing good practice. It’s a good thing we all live longer but it can be better if we live well – whether we have dementia or are related to someone who does. (291)


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: NEUROLOGICAL
Title: Emergence criteria for PDOC
Funder: Royal Hospital for Neuro-disability

Abstract: The proposed research aims to identify a wider range of tasks which can be used to more accurately determine emergence from DoC based on evidence, which will support individuals, families and healthcare providers in appropriately targeting on-going intervention and in making complex decisions about the care and management of patients in DoC.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Neural tube development
Funder: The Francis Crick Institute

Abstract: This work was supported by the Francis Crick Institute which receives its core funding from the UK Medical Research Council (FC001000), the Wellcome Trust (FC001000),and Cancer Research UK (FC001000). A central problem in biology and key to realising the potential of regenerative medicine is understanding the mechanisms that produce and organize cells in the complex tissues of an embryo. In broad terms, initially uncommitted progenitors acquire their fate in response to signals that control transcriptional programmes. These programmes drive developing cells through spatial and temporal successions of cell states that gradually refine cell identity. How these states are established and cell fate decisions implemented is poorly understood. To address this we use an experimentally tractable system – the formation of defined populations of progenitors in the vertebrate spinal cord. We will take an interdisciplinary approach. We have developed in vitro differentiation systems that use embryonic stem cells to recapitulate the in vivo development of the spinal cord. We have embraced new technologies that provide unprecedented ability to manipulate and assay single cells. Finally, we have established interdisciplinary collaborations to develop computational tools and construct data driven mathematical models. Using these approaches, alongside established embryological methods, we have established a platform for manipulating and analysing mechanisms by which the multipotent progenitors that form the spinal cord acquire specific identities. We will identify the rules by which cells make decisions and we will define the design logic and network architectures that lead to distinct cell fate choices. The ability to: (i) follow the trajectory of a cell as it transitions to a specific neuronal subtype in vivo; (ii) manipulate the process in vitro and in vivo; and (iii) model it in silico, offers a unique system for understanding organogenesis. Together these approaches will provide the knowledge and technical foundations for rational, predictive tissue engineering of the spinal cord.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL
Title: Generation of cell diversity in the brain
Funder: The Francis Crick Institute

Abstract: We study how the different types of cells that constitute the nervous system are generated at appropriate times and locations to form functional neural circuits. We address these questions using the embryonic and adult mouse brain as our main experimental models. Our aim is to identify fundamental mechanisms that underlie the generation and functioning of the nervous system, and to contribute to the development of therapies to treat neurological disorders.. The main cellular components of the nervous system, neurons and glial cells, are generated by common progenitors or stem cells, located in specialised cell layers found throughout the embryonic brain and in restricted locations in the adult brain. The choice of stem cells to divide, remain quiescent or differentiate into neurons or glial cells, is dictated by extracellular signals including morphogens such as Wnts or BMPs, and, in the adult brain, by neurotransmitters that provide feedback signals from surrounding neuronal networks. We are interested in how stem cells integrate these multiple signals to select appropriate behaviours. Although each brain region contains many different types of neurons and glial cells connected in highly specialised circuits, each stem cell usually produces only one type of neuron or glia at a particular time and place. We identify transcription factors that allow stem cells to select a particular fate, and study the mechanisms that control the precise timing of their expression and activity, including epigenetic mechanisms that control the accessibility of regulatory elements to transcription factors. The transcription factors that specify stem cell fates often also induce the differentiated phenotype of the neuronal progenies. We investigate the mechanisms that control the switch of activity and change of downstream targets of transcription factors between progenitors and differentiating neurons. We also study the gene expression programmes induced by transcription factors in differentiating neurons, and the mechanisms responsible for the sequential expression of their targets and the progressive acquisition of the neuronal phenotype. As neurons differentiate, they leave the stem cell layers where they were born and migrate to locations where they wire with other neurons and establish circuits. Neuronal migration requires the precise regulation of a large number of genes involved in cytoskeleton remodelling as well as the monitoring of environmental cues that allow neurons to follow defined routes. We study the gene regulatory programme controlling neuronal migration and its modulation by extrinsic signals that direct the migration of neurons.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: NEUROLOGICAL