Aston Brain Health Cohort Study (ABaHCoS)

Aston Brain Health Cohort Study (ABaHCoS)

Funded by the Dunhill Medical Trust, the ExtraCare Charitable Trust and Aston University, this suite of 5 PhD studentship will explore the early prediction of dementia risk. 

The five students will work together to develop simple tests that can be administered as part of an eye test, hearing test, GP health screening visit or even in the home. These methods will span psychology, neuroscience, optometry, biology, and medicine bringing a multifaceted approach to the early detection of dementia.

New treatments are becoming available for dementia, but they work by slowing the progression of the disease and are therefore most effective when used early. By detecting the disease before symptoms become apparent, individuals will be able to adopt beneficial lifestyle changes, while health providers will be able to identify individuals for follow-up monitoring and treatment.

The ABaHCoS study revolves around the idea of a Brain Health Index that is this difference between chronological age and ‘brain age’. Brain age will itself be predicted by a suite of tests that are known to correlate with chronological age but also get worse in dementia, mild cognitive impairment, and similar conditions. Thus, if a person’s predicted brain age exceeds their chronological age they may be at risk of dementia even when no symptoms are present.

The students will each research a potential diagnostic test to confirm that it individually predicts both age and dementia. These tests will then be applied to a common cohort of adults to derive a more comprehensive and reliable overall measure. Students will work together to administer the tests to the cohort.

The projects

Projects span Cognitive Psychology, Neurophysiology, Neurovascular Function and Cellular Biology and will be awarded on a competitive basis while ensuring breadth across the four themes. The final five projects will be selected from those listed below and prospective students are encouraged to apply for the projects that best match their interests and experience. However, applicants who are uncertain as to which project to apply for can apply for the Open Project.

ABaHCoS Project

Students who are interested in researching the early detection of dementia but are uncertain which of the projects below to apply for can apply for a general place and will then be guided towards an appropriate project/supervisor. For this you should apply using the project title “Aston Brain Health Cohort Study (ABaHCoS)” and select Professor Andrew Schofield (a.schofield@aston.ac.uk) as supervisor. Please note this route does not allow prospective students to choose a topic outside of the list below.

Preferred degree subjects: Biological Sciences, Biomedical Science, Psychology, Neuroscience,  Medicine, Optometry, Computer Science, or a related discipline.

Cognitive Theme projects

Project 1: Developing theoretically informed cognitive markers for Alzheimer’s Disease (AD)

Main Supervisor: Dr Mathew Buckley, m.buckley@aston.ac.uk
Associate Supervisors: Prof Adrian Burgess, Dr Irundika Dias
External Advisors: Prof Anthony McGregor, Dr Tom James.
Co-funded by the ExtraCare Charitable Trust
Preferred degree subjects: Psychology, Neuroscience or a cognate discipline.
Preferred skills: Knowledge/experience of analysing EEG recordings.
Key words: Alzheimer’s disease, Navigation, EEG, biomarkers.

Cognitive markers of AD offer the potential for self-administered tests that act as gatekeepers for biological or neurophysiological assessment. However, many cognitive tests aimed to detect AD-related pathology are optimised to discriminate AD, MCI, and healthy ageing, such that individuals in the very early stages of AD appear cognitively normal on these tests. Moreover, one of the main rationales for advancing a given cognitive task as a potential marker for AD is that the tasks is thought to rely on the hippocampus, one of the first brain regions damaged by AD. But this is overly simplistic, given that early AD-related neuropathology is generally considered to be heterogeneous.

The successful candidate will work on a project in which various navigational tests will be administered via desktop virtual environments (to include both online and in-person testing). These tests have been designed to assess if reinforcement learning can offer a cognitive theoretical framework for understanding and predicting healthy and pathological ageing. The work in this studentship will also involve relating navigational assessments to biomarkers and genetic risk of AD, and an exploratory brain age measure using EEG alpha recordings, to determine if deficits in particular navigational behaviours are related to biological signals of early AD-pathology.

Project 2: Identifying the neurocognitive sources of age-related decline in cognition: A cognitive neuroscience approach.

Main Supervisor: Dr Dan Shaw, d.j.shaw@aston.ac.uk
Associate supervisors: Dr Craig Hedge, Dr Charlottle Pennington Dr Matthew Buckley
Co-funded by the Dunhill Medical Trust
Preferred degree subjects: Psychology, Neuroscience, or a related discipline.
Preferred skills: Experience with cognitive neuroscience research methods (using functional MRI/MEG/EEG). Programming skills (MATLAB, Python, R or similar). Knowledge of general statistics for data analysis. Key words: Ageing, brain health, social cognition, spatial navigation, executive functioning.

Ageing is associated with declines in a range of cognitive abilities, including Theory of Mind (ToM), spatial navigation, executive functioning and processing speed. In all these domains, an accelerated rate of decline is observed in dementia. 
A challenge to the development of efficient cognitive assessments for brain health is that there is both unity and diversity in our cognitive architecture. For example, while ToM tasks attempt to assess our specific ability to attribute mental states to others, age-related difficulties in these tasks appear to reflect upstream disruptions to domain-general response speed, attention, and working memory. Similarly, navigation is believed to be underpinned by these executive functions. This project will determine if so-called “domain-specific” cognitive abilities (i.e. ToM, spatial navigation) decline with age in parallel, or whether they share one or more domain-general root causes. 

The project will utilise behavioural and neuroimaging data. The cognitive domains highlighted above are associated with distinct neural substrates and characteristics, which may mediate age-related changes in cognition above and beyond task performance.  For example, age-related changes in processing speed, which underpin deteriorations in executive functions, have been linked to decreased myelination. A series of studies complimenting will examine whether the relationship between age-related decline on tasks measuring ToM and spatial navigation can be accounted for by reduced executive functioning and processing speed. This will enable us to identify optimal predictors of brain age that can be applied to detect the very early signs of dementia.

Project 3: Improving early diagnosis of dementia: Self-administered, repeatable cognitive measures and relationship with chronological age and biomarkers.   

Main Supervisor: Dr Cristina Romani.  C.Romani@aston.ac.uk
Associate Supervisors: Dr Nathan Ridout, Dr Craig Hedge, Dr Lucy Bastin,
External Advisor: Dr Andrew Olson.
Co-funded by the Dunhill Medical Trust
Preferred degree: Psychology, Neuroscience or Computer Science.
Preferred skills: requirements include knowledge/experience of cognitive testing, statistical analyses, computer presentation of cognitive tasks (e.g., using Pavlovia, PsychoPy, Eprime, etc.), using large databases. 
Key words: Dementia, neurocognitive disorders, mild cognitive impairments, early diagnosis, cognitive assessment, neuropsychology, biomarkers

This PhD offers a fully-funded, unique opportunity to advance our understanding of neuro-cognitive degenerative diseases.  The successful candidate will focus on identifying optimal cognitive measures for early detection of impairment, but s/he will work in close collaboration with other students of the Aston Brain-Health-Cohort Study to gather neuroimaging, perceptual, neurovascular, and cellular-health measures from the same participants.  This will allow the project to validate cognitive measures using independent biomarkers of disease and, at the same time, to identify biomarkers which have functional consequences. 

Cognitive testing is crucial for early detection of neurodegeneration and for assessing the efficacy of pharmacological treatment.  However, the literature has reported limited sensitivity for commonly used batteries and tasks because of several limitations. 

1. Commonly used batteries include only a limited number of tasks, while people differ in the cognitive areas and tasks which are impaired in the initial stages of disease.  This project will use a comprehensive set of tasks but reduce the burden of administration by digitalization.  
2. Individual Impairment is generally established against a comparison population.  However, cognitive abilities are very variable, even when age and education are controlled.  This project will repeat testing within the same individual using matched versions of tasks to assess deterioration.
3. Mood disorders may affect cognition, complicating diagnosis. We take possible depression and anxiety into consideration. In the literature, validation is often through related cognitive tests.  This project will allow validation through independent biomarkers.

The successful student will: 

• Learn to administer gold-standard neuropsychological tasks available in the ‘toolbox’ of clinical/experimental neuropsychologists. These tasks will cover areas such as executive functions (e.g., with tasks such as the trail-making test, verbal fluency, the Stroop task, monitoring and go-no-go tasks), memory (e.g., digit span, Corsi span, the Rey Auditory-Verbal-Learning-Test), speed of processing of visual attention (e.g., search tasks), and language (e.g., lexical decision, naming to definition and spelling).   
• Learn to devise new tasks and/or modify existing tasks following the needs and the feedback of potential uses (e.g., probing more areas such as navigational and prospective memory).  
• Develop skills to digitalize tests so that they can be easily administered and scored.
• Acquire background knowledge in closely related areas (e.g., neuroimaging).  

We are looking for an ambitious and motivated student with excellent academic and interpersonal skills who aims to become a leader in the assessment and treatment of neuro-cognitive disorders and who will thrive in a vibrant interdisciplinary research community of experienced supervisors and equally motivated students.  The studentship will train a well-rounded neuropsychologist with an excellent multidisciplinary background who will be equally at ease working in a variety of settings from clinical, to academic, to third sector (advocacy, commercialization of neuropsychological assessment tools).  

Neurophysiological theme

Project 4: Estimating Brain Age using a motion judgement task and magnetic resonance imaging (MRI).

Main Supervisor: Dr Samantha Strong, s.strong2@aston.ac.uk
Associate Supervisors: Prof Stephen Mayhew s.mayhew@aston.ac.uk, Prof Andrew Schofield, Dr Valia Rodriguez, Dr Adrian Burgess.
Co-funded by the Dunhill Medical Trust 
Preferred degree: Psychology, Neuroscience, Optometry, or a closely related discipline.
Preferred skills: Knowledge/experience of psychophysical testing, statistical analyses, and computer presentation of perceptual tasks (e.g., PsychoPy, Eprime, MATLAB).
Keywords: visual processing, brain age, ageing, dementia, neuroimaging, MRI

This project will combine behavioural and neuroimaging assessments of visual cortex function to produce quick, easy, computer-based radial motion tasks to be used during pre-screening within eyecare settings to predict the degree of healthy ageing within an individual. This estimate of ‘brain’ age will be compared with an individual’s chronological age, hypothesising that discrepancies between the two indicate early age-related cognitive decline or dementia.  

Many aspects of visual processing alter in older age, due to changes in the eye as well as neural and vascular changes in the brain. Older adults show more pronounced neural deficits when tasks require more processing steps and are less able to interpret complex motion, whilst ability to interpret simple motion is preserved. Older adults show large individual differences in both motion perception task performance and in the balance of excitation and inhibition (EIB) in sensory cortex. EIB assessed by functional magnetic resonance imaging (MRI) alters as early as 40 years of age, but a subset of older individuals showed maintained EIB levels, suggesting a potential protective mechanism.  This project aims to elucidate the mechanisms underlying these effects and develop tests to probe them, whilst controlling for age-related optical deterioration by considering lens clarity, pupil size, and contrast sensitivity as covariates. Young adult behaviour will also be modelled, using filters to simulate ageing, to help predict ‘healthy’, optical, deterioration.  

Older adults will discriminate the direction of radial motion in random dot displays using an adaptive threshold estimation measure similar to hearing tests. Whilst this task is well established for normal visual processing it has not previously been used to assess neural decline.

MRI will provide non-invasive quantification of brain parameters to understand age-related changes in visual perception vis measurement of EIB, controlling for changes in neurovascular coupling, and providing wider metrics of brain health such as alterations in functional and structural connectivity across whole-brain networks.  

This project will acquire a unique battery of neuroimaging and psychophysical measures which can identify the most important neurobiological parameters of brain health and the onset of dementia, as well as providing neuroimaging correlates with cognitive and biological parameters obtained in other ABaHCoS projects.

Neurovascular theme

Project 5: Haemostatic dysregulation as a marker of blood-brain barrier malfunction – a novel predictor of brain age

Main Supervisor: Dr Caroline Kardeby, caroline.kardeby@aston.ac.u
Associate Supervisors: Dr Lissette Sanchez-Aranguren sanchel2@aston.ac.uk, Dr Valia Rodriguez, Dr Irundika Dias
Co-funded by the Dunhill Medical Trust
Preferred degree: biomedical sciences, biological sciences, pharmacology, neurosciences, or medicine.
Preferred skills: 1. Knowledge/experience of working with human samples, particularly serum and plasma. 2. Experience in culturing human cells, preferably primary endothelial cells.  
Keywords: Brain-health, blood-brain barrier, endothelial dysfunction, platelet reactivity, lipid oxidation, vascular health

An important driver in the pathophysiology of dementia is the breakdown and malfunction of the blood-brain barrier (BBB). When the BBB becomes damaged, the vascular permeability increases leading to blood cells and inflammatory components being able to infiltrate the brain. In dementia, especially Alzheimer’s disease, the BBB weakens and up to 78% of patients experience microbleeds in the brain. Moreover, a steady decrease in the function of the BBB is accompanied by endothelial dysfunction which further enhances the pathological process of slowly proceeding to dementia. The changes to the BBB leading to dementia are slow, silent, and progressive in nature. We believe that the changes could be detected earlier in life before the onset of clinical signs and symptoms. 

Dysfunctional primary haemostasis is an emerging observation that strongly links to dementia. Lesions in BBB result in inflammation which activates platelets as a physiological response to cover the vascular lesions.  In 2022, a study showed that increased platelet reactivity is associated with dementia and can be detected 20 years before the onset of disease. Together with data from 2019 that show that platelet hyperreactivity exists in subgroups of younger healthy volunteers, we believe that it is important to further explore the role of platelet reactivity in BBB breakdown. 

The PhD candidate will use blood samples from the ABaHCoS cohort to study platelet reactivity and quantify blood biomarkers, e.g., proteins involved in inflammation-driven thrombosis (thromboinflammation). The candidate will mimic the BBB in vitro using brain microvascular endothelial cells and assess the plasma-effect on the barrier function by investigating tight junctions, cell viability, migration, proliferation, and mitochondrial function. In addition, digital thermal monitoring, a non-invasive technique to assess vascular function in our participants will be used to allow us to correlate vascular health status with our mechanistic results.

 

Project 6: Understanding the link between vascular health, ageing, and early declines in the battle against Dementia.

Main Supervisor: Dr Valia Rodriguez, v.rodriguez@aston.ac.uk
Associate Supervisors: Dr Irundinka Dias, Prof Stephen Mayhew, Dr Lissette Sanchez-Aranguren, Dr Caroline Kardeby.
Co-funded by the Dunhill Medical Trust
Preferred degree: medicine, psychology, neuroscience, neurophysiology, biology, biomedical sciences, optometry
Preferred skills: Prior research experience, ability to work collaboratively in a team, good grasp of statistical analysis and quantitative methods, along with excellent communication skills. Computational skills are desirables. We expect the candidate to have an interdisciplinary mindset and a genuine passion for understanding the intricacies of the nervous system and its functions.
Keywords: ageing, functional decline, neurovascular ageing, inflammation, brain, retina, MRI, OCTa, EEG

Neurovascular ageing involves natural changes in the structure and function of brain blood vessels during the ageing process. This includes modifications in the vascular system, affecting blood flow, vessel integrity, and the response to regulatory signals. The process is linked to age-related conditions like cognitive decline and vascular dementia, as well as Alzheimer's disease. Understanding neurovascular ageing is vital for identifying and developing interventions to enhance brain health in the ageing population and prevent conditions such as dementia.

This project will investigate the connection between neurovascular ageing and early age-related decline in waking speed and memory. The decline in walking speed (WS) is one of the leading causes of functional deterioration at an older age, provoking falls, dependence, and early death. Interestingly, waking speed deterioration has been associated with the development of cognitive decline and with transitioning from mild cognitive impairment (MCI) to dementia.  On the other hand, subjective memory complaint (SMC)  -also called self-reported memory decline- is another type of age-related early deterioration that has also been found to be related to the risk of future dementia.
Under the hypothesis that these declines are linked to accelerated neurovascular ageing resulting from chronic inflammatory responses, we plan to study a cohort of healthy older adults and samples from older individuals experiencing WS decline and SMC. As part of your PhD, you will use cutting-edge brain and retina imaging techniques to characterise the participants’ brain vascular profile linked to their functional status. You will also investigate the correlation between inflammation markers present in blood and the vascular profile.

Besides contributing to a better understanding of neurovascular ageing, this project will identify potential targets for early diagnosis and rehabilitation of early declines, aiming to prevent dementia and bridge the gap between health and life span.

Cellular biology theme

Project 7: Role of extracellular vesicles (EV) in neuron-astrocyte intercellular communication in neuronal death

Main Supervisor: Dr Mariaelena Repici, m.repici@aston.ac.uk
Associate Supervisor: Prof Andrew Devitt
Co-funded by the Dunhill Medical Trust
Preferred degree: Biology, Biomedical Sciences or Neurosciences
Preferred skills: knowledge/experience of cell culture and microscopy
Keywords: extracellular vesicles, neuron-astrocyte communication, oxidative stress, cell death
 

Astrocytes are the most abundant glial cells in the mammalian brain. They have a neuroprotective effect on neurons by providing antioxidative function through glucose metabolism, releasing neurotrophic factors, reducing pro-inflammatory cytokines and removing toxic aggregates. On the other hand, in stress conditions, stimuli released from damaged neurons can induce neurotoxic / damaging astrocytes that trigger neuronal death. Recently, the discovery of extracellular vesicles (EV) as important intercellular communicators has introduced a new perspective to this network. EV are heterogeneous populations released by neurons and glia, and play a key role in synaptic activity, morphological plasticity, and neurovascular integrity. EV can also transfer disease-related molecules across the blood-brain barrier and can be detected in patients’ blood.

The aim of the project is to define the functional significance of EV components in neuroprotection/neurodegeneration, to identify the role of EV-mediated neuron-astrocyte intercellular communication.  We hypothesise that EV from healthy astrocytes (astrocyte-derived extracellular vesicles) protect neurons from oxidative stress and that this mechanism is perturbed in aging as well as neurodegeneration. The identification of the functional molecular cargo of astrocyte-derived extracellular vesicles in stress conditions will provide us with essential tools to identify early neuronal death and will help to define new strategies to prevent neurodegeneration.

To achieve this aim, we will:

1. generate differentiated neuron and astrocyte mono or co-cultures from human iPSC and validate their sensitivity to oxidative stress  
2. evaluate the effect of EV from healthy astrocytes on co-cultures of neurons and astrocytes in  in oxidative stress conditions, as well as the effect of EV from degenerating neurons on co-cultures of neurons and astrocytes in in control conditions
3. define the functional significance of the molecular cargo (proteomic, enzymatic activity, RNA sequencing) of such EV 
4. Investigate changes in neuronal derived EV in the brain cohort to validate our in vitro results  

The successful student will gain training in a multitude of techniques, ranging from iPSC generation and differentiation of neurons and astrocytes, confocal imaging, isolation and analysis of extracellular vesicles, western blot, flow cytometry, as well as specialized techniques including liquid chromatography mass spectrometry (LC/MS) and proteomic analysis. 

Support and training

These studentships include a fee bursary to cover the Home fees rate, plus a maintenance allowance. The allowance for 2024/5 is yet to be announced, but it is expected to be around £19,000. Up to £17750 of research and training support will also be provided over the period of the project. 

Students will benefit from a tailored training programme including a range of research methodologies, open science, and research integrity training as well as dementia awareness training and placement visits provided by our partner ExtraCare.

Entry requirements

Candidates should have been awarded, or expect to achieve, EITHER: a] a First or Upper Second Class award in their Undergraduate Degree (Bachelors or UG Masters) from a UK institution, in a subject judged by Aston to be relevant to the proposed research. OR b] a Merit (or above)* in a Postgraduate Masters degree in a relevant subject AND an Undergraduate Degree (Bachelors or UG Masters), both from UK institutions. Please see individual project descriptions for preferred degree subjects.

Qualifications from overseas institutions will be also considered but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria. For financial reasons, These studentships are only available to Home students.

*where applicable

Desirable skills for all projects include:

• Research project in a related area of study. 
• Strong organisation and time-management skills.
• Strong commitment, flexibility and independence.
• A positive problem-solving attitude and strong teamwork skills.
• Strong communication skills including excellent English language skills see here for more details). 

Application Process

Prospective students are encouraged to apply for one of the five competitive studentship listed above. Applications should be made to the Aston Graduate School. On the initial application portal:

1. Select the College of Health and Life Sciences, 
2. October Entry, 
3. Full-Time attendance, 
4. Postgraduate Research. 
5. Under degree programme select Research in Health Sciences. 
6. When asked to provide a project proposal, please indicate the title of the project and the name of the supervisor as listed above. Then detail how your knowledge and experience will benefit the project accompanied by a brief review of relevant research literature. 

Students who are uncertain as to which project to apply for and therefore wish to apply for the Open Project should use the title “Aston Brain Health Cohort Study (ABaHCoS)” and select Professor Andrew Schofield their initial supervisor and then outline their skills and experience together with a more general literature review on dementia diagnosis.