Importance of patient and public involvement in doctoral research involving people living with dementia.

BACKGROUND: There is increasing recognition of the need to include patients and the public in the research process. There is extensive literature about patient and public involvement (PPI) in research, but fewer articles report on PPI in doctoral research. AIM: To reflect on establishing an advisory group for a doctoral study, exploring the opportunities and challenges associated with including patients with dementia in the research process. DISCUSSION: The authors discuss the practicalities of establishing an advisory group, the challenges of being a novice researcher, long-term commitment to PPI, the overall approach to PPI and ethical considerations. CONCLUSION: Establishing an advisory group for a doctoral study can facilitate mutual learning and enhance the study's quality. IMPLICATIONS FOR PRACTICE: Achieving high-quality PPI in health and social care research can ultimately improve its quality and relevance. An important aspect of the doctoral journey is developing knowledge and skills to facilitate PPI as part of a researcher's apprenticeship.

APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge.

The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response: two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses in mice expressing human APOE to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNA sequencing (RNA-seq) highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia display increased Hif1α expression and a disrupted tricarboxylic acid (TCA) cycle and are inherently pro-glycolytic, while spatial transcriptomics and mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. Taken together, our findings emphasize a central role for APOE in regulating microglial immunometabolism and provide valuable, interactive resources for discovery and validation research.

The clinical decision-making process involved in end of life care for people with dementia in primary care: A protocol paper.

AIM: This article is a report of a study protocol designed to explore what factors inform healthcare professionals' clinical decision-making when providing end of life care for people with dementia in primary care. DESIGN: The proposed study will adopt a qualitative study design, utilizing an ethnographic approach. METHODS: A mixed sample group of registered healthcare professionals, including district nurses, specialist nurses and general practitioners, will be purposively sampled and recruited from one health board in Wales, which will cover three settings in primary care. A multi-method approach will be utilized to provide rich data, including non-participant observation, semi-structured interviews, and review of key documents. Data will be managed using NVivo 12 and analysed thematically. Ethics approval was gained in April 2022. DISCUSSION: Little is known about the end of life care decision-making process of healthcare professionals caring for people with dementia in primary care settings. This study will therefore address this pertinent gap. The study findings may also be transferable to healthcare professionals working in similar clinical settings across the UK. IMPACT: It is anticipated that this study will inform the subsequent development of an intervention that can be used by healthcare professionals to support decision making and subsequently the provision of quality end of life care in primary care for people with dementia.

Enhancing the clinical supervision experience of staff members working within primary and community care: a best practice implementation project.

OBJECTIVES: The project aimed to assess compliance with evidence-based criteria regarding the use of clinical supervision amongst district nurses and to improve knowledge and engagement in clinical supervision activities within the workplace. INTRODUCTION: It is important to provide clinical support to all healthcare workers that provide opportunities to develop and be listened to in a supervised environment. Clinical supervision is seen as a key element to provide this support. It provides a professional working relationship between two or more members of staff where the reflection of practice and personal emotion can be discussed, which is outlined in many policies and guidelines. METHODS: A baseline audit was carried out using the JBI Practical Application of Clinical Evidence System program involving 16 participants in one district nursing team in South Wales. The first step involved the development of the project and generating the evidence. Following this, a baseline audit was conducted, and educational training on clinical supervision was undertaken followed by clinical supervision sessions. A postimplementation re-audit was conducted following implementation. RESULTS: A total of 16 participants enrolled on the project. Receiving basic training and participating in clinical supervision was much higher than the baseline audit with both increasing to 100% compliance. Furthermore, 94% of participants were aware of clinical supervision activities and 88% knew of existing records on clinical supervision. The project results show a large increase in compliance with all of the criteria. CONCLUSION: Overall the implementation project achieved an improvement in evidence-based practice regarding clinical supervision in primary care.

APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis.

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field. METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4. RESULTS: Single-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of 13C-glucose in E4 mice and astrocytes, which showed decreased pyruvate entry into the TCA cycle and increased lactate synthesis. Metabolic phenotyping of E4 astrocytes showed elevated glycolytic activity, decreased oxygen consumption, blunted oxidative flexibility, and a lower rate of glucose oxidation in the presence of lactate. Together, these cellular findings suggest an E4-associated increase in aerobic glycolysis (i.e. the Warburg effect). To test whether this phenomenon translated to APOE4 humans, we analyzed the plasma metabolome of young and middle-aged human participants with and without the Ε4 allele, and used indirect calorimetry to measure whole body oxygen consumption and energy expenditure. In line with data from E4-expressing female mice, a subgroup analysis revealed that young female E4 carriers showed a striking decrease in energy expenditure compared to non-carriers. This decrease in energy expenditure was primarily driven by a lower rate of oxygen consumption, and was exaggerated following a dietary glucose challenge. Further, the stunted oxygen consumption was accompanied by markedly increased lactate in the plasma of E4 carriers, and a pathway analysis of the plasma metabolome suggested an increase in aerobic glycolysis. CONCLUSIONS: Together, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a 'Warburg like' endophenotype that is observable in young females decades prior to clinically manifest AD.

Palliative care for community patients diagnosed with dementia: a systematic review.

Despite many efforts made by health organisations to deliver effective end-of-life care to patients with dementia, research indicates that palliative care is predominantly aimed at patients with terminal cancer, and that patients with dementia face challenges in accessing end-of-life care. This article explores the views of health professionals on providing palliative care to those patients diagnosed with dementia within the community setting. A systematic review of seven qualitative studies was performed to identify the best available evidence. The findings show that effective palliative care for patients with dementia continues being affected by many barriers and challenges. Good practice seems to be inconsistent and fragmented throughout the UK and European countries, and many health professionals are faced with difficulties associated with services and financial implications, training and education, staff support, communication, family support and dementia care.