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Visual system vulnerability in dementia: from detection to determinants

A fully funded PhD studentship at the EPSRC Centre for Doctoral Training in Digital Health Technologies

听Visual system vulnerability in dementia: from detection to determinants

Key information

Lead supervisors: and
Application deadline:听28听础耻驳耻蝉迟听2024
Interview dates:听Please note that interviews will be provisionally held on 5th and/or 6th September 2024
Project start date: 01 October 2024 or soon after
Project duration: 4听测别补谤蝉
Studentship funding:听Home tuition fees (currently 拢6,035/year) and maintenance听stipend (currently 拢22,237/year) for 4听测别补谤蝉

Background

The challenges for healthcare systems are unprecedented, exacerbated by the burdens of infectious and chronic disease, ageing populations, inequalities, fragmented systems and workforce shortages. New technological approaches are needed to harness the potential of routine and novel health data and digital solutions to enable transformational improvement of care pathways and outcomes.

Our doctoral training programme听听will address this deficit by creating a new coordinated training curriculum, partnering world-leading academic and NHS organisations and industry, such that graduates can co-create and ideate, design, develop, evaluate and implement evidence-based digital health technologies.

PhD project description

Cortical visual impairments (鈥榖rainsight鈥, not eyesight loss) are disabling consequences of dementia associated with particular diagnostic and management needs. Such impairments have been reported in the majority of people with Alzheimer鈥檚 disease, particularly in posterior cortical atrophy (鈥榲isual-led dementia鈥) where these symptoms precede loss of memory, language and insight.

People with dementia-related visual impairment are usually seen first by eye health professionals. They are frequently misdiagnosed with eye or psychological conditions, repeatedly change glasses or undergo surgery before determining their visual loss arises from cortical, rather than ocular deficits. Tests of cortical visual function are used rarely except by highly specialised neurology/neuro-ophthalmology diagnostic services. These diagnostic scenarios often delay diagnosis and treatment for years.

Key knowledge gaps and significance:

  • There is a lack of tests to detect brainsight loss and distinguish this from eyesight loss.
  • There is a gap in evidence-based tests to diagnose brainsight loss caused by dementia. There is a gap in tests suitable across eye and dementia clinic settings.
  • The reasons behind why some people with dementia are more susceptible to brainsight loss are largely unknown.

Determining the causes and consequences of visual system vulnerability in dementia has important fundamental and translational implications for understanding variable disease onset and progression.

Project outcomes include promoting equitable access to novel disease-modifying therapies targeting Alzheimer鈥檚 disease (the most common atypical form of Alzheimer鈥檚 disease is visual-, not memory-led).

Project aims and objectives

Aim 1: Improve detection of visual-led dementia
Objective: Develop a test to detect dementia-related visual impairment in eye and dementia clinics

Aim 2: Evaluate factors associated with cortical visual function in UK Biobank
Objective: Derive a cortical visual factor in UK Biobank and evaluate candidate associated risk factors

Aim 3: Evaluate factors associated with visual system vulnerability in dementia
Objective: Compare genetic variants associated with cortical visual functioning and visual-led dementia

This studentship will incorporate neuropsychological and visual psychophysics, statistical and imaging genetics methodologies across three Projects:

Project 1: Developing and validating a cortical visual test
We have developed a digital test (Graded Incomplete Letter Test [GILT]) to rapidly detect and distinguish cortical visual from ocular losses. The GILT is adapted from standard tests to diagnose cortical visual impairment but is optimised for sensitivity and specificity. You will support validation of the GILT in ageing cohorts (UKB n=60,000) and dementia and eye clinic patients (National Hospital of Neurology and Neurosurgery, Moorfields Eye Hospital). You will relate GILT performance to clinical diagnoses and MRI and evaluate approaches to increase GILT sensitivity to damage to visual cortex.

Project 2: Confirmatory factor analysis
You will derive a cortical visual factor score in UK Biobank using confirmatory factor analysis. This factor will index cortical visual integrity by incorporating visual tests (similar to a 鈥榣anguage factor鈥 incorporating tests of vocabulary, comprehension and reading speed) and MRI measures. Analyses will be informed by separate confirmatory factor analysis of existing visual and MRI 香港六合彩中特网 patient data. You will evaluate relationships between this cortical visual factor score, Alzheimer鈥檚 disease risk factors and UK Biobank measures of functional status (e.g. time spent driving, walking pace).

Project 3: Discovery analysis
You will conduct a genetic analysis (known as genome wide association analysis or GWAS) to discover genetic markers (known as SNPs) associated with the Project 2 factor score. You will compare SNP effects with genetic profiles of visual-led dementia using adjusted logistic and linkage disequilibrium score regression. Visual-led dementia groups will include the posterior cortical atrophy sample at 香港六合彩中特网 and Alzheimer鈥檚 disease patients with predominant visual loss participating in data-sharing initiatives.

Person specification

  • Applicants are preferred to have a first-class undergraduate and/or master鈥檚 degree (or equivalent) in a numerate discipline, preferably in mathematical, computational, biological, engineering or physical sciences subjects or a related discipline, with an interest in using technology to solve health problems.
  • Excellent organisational, interpersonal and communication skills, along with an interest in interdisciplinary research, are essential.
  • Experience in computer programming is essential.
  • Fluency and clarity in spoken English as well as good written English in accordance with 香港六合彩中特网 English requirements (TOEFL>92 or IELTS>6.5).

Eligibility

Please note that the available funding supports听tuition fees at the Home/UK rate (currently 拢6,035听per year). Students who are eligible to pay fees at the UK rate are welcome to apply听(e.g. UK听students or EEA or Swiss听nationals听who are 鈥渟ettled鈥 or 鈥減re-settled鈥 within the UK in accordance with the听EU Settlement Scheme).听Please refer to our website for further information about Home tuition fee eligibility.

Applicants whose first language is not English are required to meet 香港六合彩中特网's English language entry requirements.

Please refer to this webpage for full eligibility criteria:听Mechanical Engineering MPhil/PhD

How to apply

Eligible applicants should听听by 28th August 2024. You will need a CV, academic transcript, contact details of at least two academic referees, and a personal statement giving your reasons for applying and an outline of your research interests.

  • Please select: 鈥榊ear of entry: 2024-2025 and 鈥楻esearch Degree: Mechanical Engineering鈥
  • The duration of the PhD is four years
  • The funding for this studentship is the 鈥榯ech4health programme鈥
  • You do not need to upload a 鈥榬esearch proposal鈥
  • Please write 鈥楧r Keir Yong鈥 in the 鈥榩roposed supervisor鈥 box on the application form

The supervisory team will arrange interviews for short-listed candidates.听Please note that interviews will be provisionally held on听5th and/or 6th September 2024.