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Mitochondria are intracellular organelles responsible for oxidative phosphorylation. They contain their own DNA which encodes some components involved in oxidative phosphorylation. Mitochondrial DNA is very susceptible to mutations. Mitochondrial abnormalities have been observed in several disorders of muscle and brain. Alzheimer's disease is a form of dementia characterized by the formation of numerous neuritic plaques and neurofibrillary tangles. There is evidence suggesting a possible role for mitochondrial abnormalities in Alzheimer's disease. The goal of this project was to determine if there were quantitative changes in mitochondrial DNA content in large neurons from Alzheimer's disease patients, compared to age-matched control patients. The relative mitochondrial DNA content per unit area was assessed in brain sections from Alzheimer's disease subjects and age-matched control subjects using in situ hybridization to mitochondrial DNA. The results were not conclusive due to technical concerns with the in situ hybridization technique which are discussed. / Thesis / Master of Science (MS)

Yes / Alzheimer’s disease irrevocably challenges a person’s capacity to communicate with others. Earlier research on these challenges focused on the language disorders associated with the condition and situated language deficit solely in the limitations of a person’s cognitive and semantic impairments. This research falls short of gaining insight into the actual interactional experiences of a person with Alzheimer’s and their family. Drawing on a UK data set of 70 telephone calls recorded over a two-and-a-half year period (2006–2008) between one elderly woman affected by Alzheimer’s disease, and her daughter and son-in-law, this paper explores the role which communication (and its degeneration) plays in family relationships. Investigating these interactions, using a conversation analytic approach, reveals that there are clearly communicative difficulties, but closer inspection suggests that they arise due to the contingencies that are generated by the other’s contributions in the interaction. That being so, this paper marks a departure from the traditional focus on language level analysis and the assumption that deficits are intrinsic to the individual with Alzheimer’s, and instead focuses on the collaborative communicative challenges that arise in the interaction itself and which have a profound impact on people’s lives and relationships.

Yes / The aim was to investigate the comorbidity profile of people with dementia and examine the associations between severity of comorbidity, health-related quality of life (HRQoL) and quality of life (QoL). The improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort consisted of 1,547 people diagnosed with dementia who provided information on the number and type of comorbid conditions. Participants also provided ratings of their health-related and dementia-specific QoL. The majority of the sample were living with more than one chronic condition. Hypertension was commonly reported and frequently combined with connective tissue disease, diabetes and depression. The number of comorbid conditions was associated with low QoL scores, and those with severe comorbidity (≥5 conditions) showed the greatest impact on their well-being. Comorbidity is an important risk factor for poor QoL and health status in people with dementia. Greater recognition of the nature and impact of comorbidity is needed to inform support and interventions for people with dementia and a multidisciplinary approach to care provision is recommended. / The IDEAL study is funded by the Economic and Social Research Council (UK) and the National Institute for Health Research (UK) through grant ES/L001853/2 ‘Improving the experience of dementia and enhancing active life: living well with dementia’

Yes / . Negative impacts of the COVID-19 pandemic on people with dementia have been widely-documented, but most studies have relied on carer reports and few have compared responses to information collected before the pandemic. Objective. We aimed to explore the impact of the pandemic on community-dwelling individuals with mild-to-moderate dementia and compare responses with pre-pandemic data. Methods. During the second wave of the pandemic we conducted structured telephone interviews with 173 people with dementia and 242 carers acting as informants, all of whom had previously participated in the IDEAL cohort. Where possible we benchmarked responses against pre-pandemic data. Results. Significant perceived negative impacts were identified in cognitive and functional skills and ability to engage in self-care and manage everyday activities, along with increased levels of loneliness and discontinuity in sense of self and a decline in perceived capability to ‘live well’. Compared to pre-pandemic data there were lower levels of pain, depression and anxiety, higher levels of optimism, and better satisfaction with family support. There was little impact on physical health, mood, social connections and relationships, or perceptions of neighbourhood characteristics. Conclusion. Efforts to mitigate negative impacts of pandemic-related restrictions and restore quality of life could focus on reablement to address the effects on participation in everyday activities, creating opportunities for social contact to reduce loneliness, and personalised planning to reconnect people with their pre-COVID selves. Such efforts may build on the resilience demonstrated by people with dementia and carers in coping with the pandemic. / ‘Identifying and mitigating the individual and dyadic impact of COVID-19 and life under physical distancing on people with dementia and carers (INCLUDE)’ was funded by the Economic and Social Research Council (ESRC) through grant ES/V004964/1. Investigators: Clare, L., Victor, C., Matthews, F., Quinn, C., Hillman, A., Burns, A., Allan, L., Litherland, R., Martyr, A., Collins, R., & Pentecost, C. ESRC is part of UK Research and Innovation (UKRI). ‘Improving the experience of Dementia and Enhancing Active Life: living well with dementia. The IDEAL study’ was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR) through grant ES/L001853/2. Investigators: L. Clare, I.R. Jones, C. Victor, J.V. Hindle, R.W. Jones, M. Knapp, M. Kopelman, R. Litherland, A. Martyr, F.E. Matthews, R.G. Morris, S.M. Nelis, J.A. Pickett, C. Quinn, J. Rusted, J. Thom. ESRC is part of UK Research and Innovation (UKRI). IDEAL data were deposited with the UK data archive in April 2020 and will be available to access from April 2023. Details of how the data can be accessed after that date can be found here: http://reshare.ukdataservice.ac.uk/854293/ ‘Improving the experience of Dementia and Enhancing Active Life: a longitudinal perspective on living well with dementia. The IDEAL-2 study’ is funded by Alzheimer’s Society, grant number 348, AS-PR2-16-001. Investigators: L. Clare, I.R. Jones, C. Victor, C. Ballard, A. Hillman, J.V. Hindle, J. Hughes, R.W. Jones, M. Knapp, R. Litherland, A. Martyr, F.E. Matthews, R.G. Morris, S.M. Nelis, C. Quinn, J. Rusted. L. Clare acknowledges support from the NIHR Applied Research Collaboration South-West Peninsula. The views expressed are those of the author(s) and not necessarily those of the ESRC, UKRI, NIHR, the Department of Health and Social Care, the National Health Service, or Alzheimer’s Society. The support of ESRC, NIHR and Alzheimer’s Society is gratefully acknowledged.

Yes / Global initiatives that promote public health responses to dementia have resulted in numerous countries developing new national policies. Current policy guidelines in England, for example, recommend that people diagnosed with mild-to-moderate dementia receive information and psychosocial interventions to improve their ability to ‘live well’. However, it remains unclear to what extent these recommendations are being achieved. Methods: Self-reported information from 1537 people living with dementia and informant-reported information from 1277 carers of people living with dementia was used to quantify receipt of community-based dementia support services, including health and social care services provided by statutory or voluntary-sector organisations, in Britain from 2014 to 2016. Demographic factors associated with differences in receipt of support services were also investigated to identify particularly vulnerable groups of people living with dementia. Results: Both self- and informant reports suggested that approximately 50% of people living with dementia received support services for dementia. Receipt of support services was lower among people living with dementia who are older, female, and have fewer educational qualifications. Receipt of support services also differed according to diagnosis and carer status, but was unrelated to marital status. Conclusions: Limited receipt of dementia support services among people living with dementia in Britain provides a baseline to assess the efficacy of current policy guidelines regarding provision of information and support. Targeted efforts to facilitate receipt of support services among the particularly vulnerable groups identified in the current study could improve the efficacy of dementia support services both in Britain and internationally, and should inform policy development. / The IDEAL study’ was funded jointly by the Economic and Social Research Council (ESRC) and the National Institute for Health Research (NIHR) through grant ES/L001853/2. The IDEAL‐2 study’ is funded by Alzheimer's Society, grant number 348,AS‐PR2‐16‐001.

Yes / This qualitative study was designed to understand the impact of social distancing measures on people with dementia and carers living in the community in England and Wales during a period of social restrictions before the COVID-19 vaccination roll-out. We conducted 12 semi-structured interviews with people with dementia aged 50-88 years, living alone or with a partner, and 10 carers aged 61-78 years, all living with the person with dementia. Three of the interviews were with dyads. Participants were recruited during November and December 2020. We used framework analysis to identify themes and elicit suggestions for potential solutions. We identified three interrelated themes. People with dementia experienced a fear of decline in capabilities or mood and attempted to mitigate this. Carers noticed changes in the person with dementia and increased caring responsibilities, and for some, a change in the relationship. Subsequently, reduced confidence in capabilities to navigate a new and hostile environment created a cyclical dilemma of re-engaging where an inability to access usual activities made things worse. People with dementia and carers experienced neglect and being alone in their struggle, alongside feeling socially excluded during the pandemic, and there was little optimism associated with the upcoming vaccine programme. People found their own solutions to reduce the effects of isolation by keeping busy and being socially active, and practising skills deemed to help reduce the progression of dementia. This and some limited local public initiatives for the general public facilitated feelings of social inclusion. This study adds understanding to existing evidence about the longer-term experience of social isolation several months into the pandemic. It highlights the importance of health and community groups and suggests how services can find ways to support, include, and interact with people with dementia and carers during and after social restrictions. / Economic and Social Research Council. Grant Numbers: ES/V004964/1, L001853, V004964. National Institute for Health and Care Research. Grant Number: ES/L001853/2. Department of Health. UK Research and Innovation. Health and Care Research Wales

Epidemiological studies are the prototype for elucidating patterns of disease based on known exposures. In this thesis, study of both case-control and cohort epidemiological studies were analyzed in the sector of Alzheimer's disease. More specifically, the scope of research involved the exposure of race, black or white, and the onset of disease. This research is significant because white based studies are predominant in Alzheimer's disease and minimal research has been done that links the relationship between race and the disease. Several epidemiological studies which include a substantial portion of the black community were reviewed and discussed. Quantitative and qualitative research in this study determined that blacks have a much higher risk than their white counterparts for obtaining the onset of Alzheimer's disease, with some studies producing an RR of 2.9 when comparing the two races. The relative risks for elucidation of causation between this linkage produced in each study varied significantly. One study analyzed and presented provided results that were largely inconsistent with other data in this project. Studies presented allowed epidemiologists and physicians to concentrate on more elusive risk factors such as the apolipoprotein e4 allele after black populations that had more of a risk of the onset of Alzheimer's disease were isolated through epidemiological research found in this thesis. In short, this project explored and discussed a sector of Alzheimer's disease that is largely unexplored and fuels additional research centering race and the disease given the projected increase in black elderly populations in the community and need for advancements in the field.