Phosphoinositides: Roles in the Development of Microglial-Mediated Neuroinflammation and Neurodegeneration

Microglia are increasingly recognized as vital players in the pathology of a variety of neurodegenerative conditions including Alzheimer’s (AD) and Parkinson’s (PD) disease. While microglia have a protective role in the brain, their dysfunction can lead to neuroinflammation and contributes to disease progression. Also, a growing body of literature highlights the seven phosphoinositides, or PIPs, as key players in the regulation of microglial-mediated neuroinflammation. These small signaling lipids are phosphorylated derivates of phosphatidylinositol, are enriched in the brain, and have well-established roles in both homeostasis and disease.Disrupted PIP levels and signaling has been detected in a variety of dementias. Moreover, many known AD disease modifiers identified via genetic studies are expressed in microglia and are involved in phospholipid metabolism. One of these, the enzyme PLCγ2 that hydrolyzes the PIP species PI(4,5)P2, displays altered expression in AD and PD and is currently being investigated as a potential therapeutic target.Perhaps unsurprisingly, neurodegenerative conditions exhibiting PIP dyshomeostasis also tend to show alterations in aspects of microglial function regulated by these lipids. In particular, phosphoinositides regulate the activities of proteins and enzymes required for endocytosis, toll-like receptor signaling, purinergic signaling, chemotaxis, and migration, all of which are affected in a variety of neurodegenerative conditions. These functions are crucial to allow microglia to adequately survey the brain and respond appropriately to invading pathogens and other abnormalities, including misfolded proteins. AD and PD therapies are being developed to target many of the above pathways, and although not yet investigated, simultaneous PIP manipulation might enhance the beneficial effects observed. Currently, only limited therapeutics are available for dementia, and although these show some benefits for symptom severity and progression, they are far from curative. Given the importance of microglia and PIPs in dementia development, this review summarizes current research and asks whether we can exploit this information to design more targeted, or perhaps combined, dementia therapeutics. More work is needed to fully characterize the pathways discussed in this review, but given the strength of the current literature, insights in this area could be invaluable for the future of neurodegenerative disease research.

Delivery of the Dementia Friends programme on the MPharm degree course: a qualitative exploration of pharmacy students’ perspectives

Introduction A person-centred approach to dementia care has been advocated1, but limited literature exists on integration of this into pharmacist undergraduate education. The Alzheimer’s Society Dementia Friends programme was developed to change peoples’ perceptions and promote understanding of living with dementia. In 2019, the School piloted provision of Dementia Friends training; Level 3 MPharm students (n=102) were invited by email to participate as an optional part of a Clinical Therapeutics module. Sixty-three students (61.8%) attended the workshop, which combined Dementia Friends training with an interactive session facilitated by a person living with dementia (PLWD). Aim To explore undergraduate pharmacy students’ views and experiences of the Dementia Friends pilot. Methods All students who had attended the workshop were invited by email to participate in a focus group during February 2020. Participants provided written informed consent. The topic guide focused on students’ views of workshop delivery, improvements that could be made, their understanding of person-centred care, and the impact of the workshop on their clinical practice. The focus group was audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results One focus group was conducted with eight students. Three overarching themes were identified: learning from an expert patient; importance of person-centred care; and dementia education during MPharm degree. Students valued the opportunity to learn from a PLWD and felt it allowed them to relate the condition to a real person: “it felt more personal so you could really connect with them [PLWD] and understand their experience”. Hearing about the ‘lived experience’ helped to contextualise learning from other methods of delivery, e.g. lectures: “you don’t know what’s going on in someone else’s life, and sometimes we’re all a bit quick to judge, I think [the workshop] put that into perspective”. Students described having greater understanding of person-centred care and taking a holistic approach to pharmaceutical care provision for PLWD: “it’s very important to take into account their quality of life…we can focus on the clinical but looking at the person as a whole actually helps their treatment” and “one of the things I found most interesting was that they might not remember the interaction but they will [retain] the feeling or emotion”. Students reported feeling more confident in engaging with PLWD following the workshop, which is something they would not have had the opportunity to learn from lectures alone: “If we hadn’t had that dementia training, I feel like I would still have no confidence chatting to dementia patients”. Students suggested that future Dementia Friends training should be delivered earlier in the MPharm degree course. Conclusion This study has shown that Dementia Friends training complemented students’ existing knowledge of dementia and increased their confidence to communicate with PLWD. The use of an expert patient was an effective way of supporting MPharm students to develop a person-centred approach to their professional practice. The study was limited to one university so findings may not be generalisable. However, these data provide a good basis for future development and evaluation of Dementia Friends training provision to MPharm students. References 1. Kitwood, T. M. Dementia reconsidered: the person comes first. 1997. Buckingham [England], Open University Press

Relationship-centred CogniCare: an academic–digital–dementia care experts interface

Purpose This paper aims to reports on an academic–industry service development innovation to advance the symptom monitor and track feature within the CogniCare app to support family carers of people living with dementia. Expert opinion from dementia care professionals identified key monitoring strategies for enhanced carer competence and confidence in the early identification of relevant symptoms that would help facilitate meaningful hospital/social care consultations. Design/methodology/approach A co-production approach between industry and academia included stakeholder representation from NHS Highland and Alzheimer Scotland. Dementia care experts validated items to be included for symptom monitoring and tracking using a newly developed A2BC2D2EF2 framework as part of this project and recommended additional strategies for monitoring symptom change, including carer well-being. Findings Dementia care experts perceived the symptom monitoring and track feature to have the potential to support family carers with dementia care at home and foster a relationship-centred approach to dementia care to facilitate meaningful hospital/social care consultations. Originality/value The CogniCare app is the first platform of its kind that aims to support family carers to care for people living with dementia at home. This unique service development collaborative combined dementia and digital expertise to create innovative digital solutions for dementia care. The proposed monitoring and tracking feature is perceived by dementia care experts as a tool with the potential to enhance carer confidence and thus enable safe and effective dementia care within the home environment.

Periodontal disease and incident dementia

ObjectiveTo test the hypothesis that periodontal disease would be associated with increased risk for dementia and mild cognitive impairment (MCI) by assessing dementia/MCI outcomes after a baseline periodontal examination.MethodsParticipants enrolled in the Atherosclerosis Risk in Communities study with a clinical periodontal examination (or edentulous participants) at visit 4 (1996–1998; mean ± SD age 63 ± 6 years, 55% female, 21% black) and adjudicated dementia outcomes through 2016 were included (n = 8,275). A subgroup of 4,559 participants had adjudicated dementia and MCI assessments at visit 5 (2011–2013). Participants received a full-mouth periodontal examination and were classified into periodontal profile classes (PPCs) based on the severity and extent of gingival inflammation and attachment loss. MCI and dementia were determined via neurocognitive testing, neurological examination and history, informant interviews, and brain MRI in a subset. Cox proportional hazards models regressed incident dementia on PPCs. Relative risk regression models were used for the composite of MCI/dementia.ResultsThe cumulative incidence and incidence density of dementia during follow-up (average 18.4 years) were 19% (n = 1,569) and 11.8 cases per 1,000 person-years. Multivariable adjusted hazard ratios for incident dementia among participants with severe PPC or edentulism (vs periodontal healthy) were 1.22 (95% confidence interval [CI] 1.01–1.47) and 1.21 (95% CI 0.99–1.48), respectively. For the combined dementia/MCI outcome, adjusted risk ratios among participants with mild/intermediate PPC, severe PPC, or edentulism (vs periodontal healthy) were 1.22 (95% CI 1.00–1.48), 1.15 (95% CI 0.88–1.51), and 1.90 (95% CI 1.40–2.58). Results were stronger among younger (≤62 years) participants (p for interaction = 0.02).ConclusionPeriodontal disease was modestly associated with incident MCI and dementia in a community-based cohort of black and white participants.

Structural validity and internal consistency of the Qualidem in people with severe dementia

ABSTRACTBackground:Since its development, the Qualidem has had items that were considered unsuited for people with very severe dementia. This study attempted to investigate the applicability of all Qualidem items in people with all stages of dementia severity.Methods:Four data sets that contained Qualidem observations on people with dementia were combined. Dementia severity was categorized based on the Global Deterioration Scale (GDS), with a dichotomization of very severe dementia (GDS 7) and others (GDS 1–6). Unidimensional latent-trait models (Mokken scaling) were estimated to fit the Qualidem responses in the overall sample and the dichotomized groups. Scalability was assessed using coefficients of homogeneity (Loevinger's H), while reliability was assessed with Cronbach's α and ρ.Results:Combining the four databases resulted in 4,354 Qualidem measurements. The scalability of all scales was considered acceptable in the overall sample, as well is in the subgroups (all H > 0.3). Additionally, the reliability was good–excellent in the scales: “positive affect,” “positive self-image,” “care relationship,” and “negative affect.” Reliability was questionable–acceptable for “feeling at home,” “social relations,” “social isolation,” and “restless tense behavior.” Reliability was poor for “having something to do.”Conclusions:Statistical considerations allow using all Qualidem items in all dementia stages. Future research should determine balance of statistical- versus conceptual-based reasoning in this academic debate.