Introduction
This is an exciting opportunity to undertake a funded PhD in a novel area of dementia research, using genetic information to investigate the causes of non memory symptoms in Alzheimer’s disease and other dementias.
Background
Behavioural and neuropsychological symptoms are very common in dementias such as Alzheimer's Disease. These behavioural and neuropsychological symptoms cause considerable distress, are difficult to treat and the underlying biology remains unclear. For example depression affects 16% and psychosis afflicts 40% of individuals with Alzheimer's Disease during the course of their disease. Current treatments often do not work and have considerable side effects.
Other behavioural symptoms e.g., anxiety, aggression, apathy and euphoria, are also seen in patients with AD and other dementias and can have a dramatic effect on the patient’s quality of life. Apathy, which affects 49% of individuals with AD is one of the most severe symptoms, which is thought to be because it is particularly persistent.
These symptoms, have largely been studied in isolation, which does not reflect the experience of individuals with disease. Identifying and utilising patient specific-, symptom specific- profiles has the potential to elucidate homogeneous forms of disease with underlying genetic and biological aetiology. There is an urgent need to understand the mechanisms underlying the manifestation of behavioural symptoms within and across dementias to develop effective treatments.
Overall Aim of the PhD
This project aims to identify genes and biological pathways that associate with behavioural symptoms of dementia that will provide novel targets for therapeutic intervention improving quality of life for those living with dementia.
Objectives
The project’s primary objectives are:
- Identifying behavioural symptom profiles within and across forms of dementia.
- Test for genetic association with specific symptom profiles.
- Test for biological pathways enriched in the dataset.
- Test for overlap of symptom profiles within relevant disease in younger adults.
- Utilise longitudinal cohorts to test for early diagnostic markers
Methodology
The student will use data from several large studies which have genetic information generously given by people with dementia. These same people and/or their carers also answered questions about non-memory symptoms of dementia. This information was mostly collected using the Neuropsychiatric Inventory (also known as the NPI). The team in Cardiff have collected data from 5000 people with Alzheimer’s Disease, 325 people with Lewy Body Dementia and 3000 controls. Additional data will be available to the student through our collaborations abroad. This will give data from an additional ~40,000 people with dementia and ~60,000 controls.
The student will gain skills in the following techniques
- Factor Analysis: To identify which non-memory symptoms tend to occur together. This will generate groups of symptoms.
- Genome-wide Association Study: To assess whether any of these groups of symptoms are associated with genetic changes.
- Pathway Analysis: To group together genes that are associated with groups of symptoms into protein pathways and to test these for excess association signal compared to
- random genes.
- Overlap Analysis: GCTA will be used to identify genetic overlap between groups of symptoms and across different types of dementia.
- Longitudinal Data: Using regression to identify if anything in earlier life predicts these symptoms
University of Bristol, Bristol Medical School
Bristol Medical School is the largest and one of the most diverse Schools in the University of Bristol, with approximately 930 members of staff and over 300 postgraduate doctoral research students. The School is a leading centre for research and teaching across Population Health Sciences and Translational Health Sciences. Research in the School is collaborative and multi-disciplinary, with staff coming from a wide range of academic disciplines and clinical specialties.
The 2021 Research Excellence Framework (REF) confirmed the University of Bristol’s position as a leading centre for health research. In the REF 2021, the results of which have only just been published 49% of research in psychology, psychiatry and neuroscience was 4* (world leading) and 35% was 3* (internationally excellent). Overall the Bristol results placed it 5th in the UK for research excellence. Within the Medical School are several major research centres, groups and programmes. More details can be found on the Medical School website.
How to apply
Apply online. Select “Population Health Sciences” PhD programme and state in the application that you are applying for funding from the James Tudor Foundation. Please ensure you have read our admissions statement before making an application. We request a 2 page research proposal from you as part of the application. This should be in your own words and an outline of the project as you understand it.
Applicants should hold (or be about to obtain) at least an upper second class honors degree or Masters degree (or equivalent) in biological sciences or a related discipline, with an genetics and/or dementia neuroscience. Candidates who have previous laboratory or bioinformatic research experience are particularly encouraged to apply. Pre-application enquires are encouraged.
Shortlisted applicants will be invited for interview in September 2022.
Enquiries: Dr Lindsey Sinclair [Email Address Removed] and Professor Patrick Kehoe [Email Address Removed]
The supervisory team also includes two honorary supervisors from Cardiff University
Closing Date: 31st August 2022
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