Dunhill Medical Trust Doctoral Training Programme for Ageing Research

The DTP for Ageing Research in Exeter will focus on two main areas and here we provide examples of potential PhD projects. (1) Improving our understanding of the mechanisms of ageing and age-related conditions In the UK, it is estimated that over 70% of older people have some form of cognitive impairment (Richardson et al., 2019).

However, there are also older people who exhibit resilience to age-dependent cognitive dysfunction.

Epigenomic changes are thought to underlie many age-associated diseases, including age-associated cognitive decline (Maity et al., 2021). It is not known how these molecular changes result in abnormal connections (synapses) between brain cells.

It is critical to understand the mechanisms responsible for cognitive decline and resilience and to start evaluating interventions that target the salient mechanisms.

Among those with cognitive impairment, there is an increasing recognition of the additional psychiatric and psychological burden that individuals face.

For example, psychotic symptoms in Alzheimer’s dementia occur in up to 50% of people and is a major driver of poor quality of life (Ismail et al., 2022).

When newly emergent in later life, psychosis confers a significantly increased risk of cognitive impairment and dementia but individuals presenting primarily with these symptoms are often not considered for memory clinic referrals, causing delays to access the right care (Creese et al., 2023, Ismail et al., 2023).

Potential PhD projects: • Linking epigenetic and synaptic mechanisms in age-associated cognitive decline and resilience.

Supervisory team: Albert Basson, Katie Lunnon and Adam Smith We recently developed robust methods to study deficits in memory updating in aged mice. Memory updating is more relevant to human ageing, as humans rarely encode completely de novo information.

We have identified specific epigenomic changes in the aged mouse hippocampus and have identified a lead compound that can normalise these abnormalities.

The aim of this project is to determine if these epigenomic changes are responsible for memory updating deficits and if specific drugs can rescue these deficits and the abnormal synapses in the aged brain.

This project will significantly advance our understanding of the age-associated changes that underlie cognitive decline. • Investigating the neurodegenerative substrates of late-life onset psychotic symptoms in cognitively normal people. Supervisory Team: Byron Creese, Zahinoor Ismail.

In older people who do not have memory problems, experiences like mild paranoid thoughts or suspiciousness are linked with a higher risk of later dementia.

Identifying people with early-stage disease is important because it could help doctors manage care better and help recruit people into trials of new drugs for diseases like Alzheimer's. This project aims to identify whether mild paranoid thoughts are associated with brain changes found in early dementia.

If we can confirm this, then we may be able to identify people with early disease through a simple questionnaire in the future. (2) Preventing, delaying or reducing health and social care needs, maintaining functional independence Around a third of older people and half of care home residents fall each year with significant impact on the individual and families, the NHS, and social care services.

Walking frames can provide structural support during walking and are used by many older people.

Counter-intuitively, a systematic review identified general walking aid use to be a risk factor for falling and those who self-report using frames remain more likely to fall than people who do not (Deandrea et al., 2010).

Incorrect walking aid use is associated with falling (Thies et al., 2020a) and 60% of users report problems with their walking frame (Skymne et al., 2012). Clearly there is scope for improving safe mobility in walking aid users.

There is a lack of ecologically valid research investigating safe movement in real-world scenarios e.g. the home, community or healthcare settings in older people who often have reduced sight, hearing, proprioception and mobility. Potential PhD projects • Using walking aids safely in hospital.

Supervisory team: Helen Dawes, Mae Mansoubi, Sibylle Thies Our team have carried out studies that have determined the biomechanics of safe walking frame use and important aspects regarding how to best train walking aid use, in people with and without cognitive impairments, and developed a simple monitoring/feedback technology (Thies et al., 2020b, Lee et al., 2022, Thies et al., 2020a, Lee et al., 2023).

Recent advances in technology mean that walking aid use can be objectively monitored in clinical settings.

When older people go into hospital, they may be trained by physiotherapists how to use a walking frame to reduce their risk of falling. Training requires regular practice with feedback on safe use. Currently, practice is limited by therapy time.

This PhD aims to 1) validate the simple technology to monitor safe and unsafe frame use in older people in hospital settings and 2) determine the usability of the frame training technology to augment current physiotherapy services in hospitals. The PhD will lead to a feasibility trial of the system. • Life space mobility and wellbeing of care home residents.

Supervisory team: Vicki Goodwin, Abi Hall, Jo Day Mobility is the ability to move around in an environment including the home, the community and beyond and can be defined in terms of ‘life space’.

Being outdoors and trips outside the care home to improve residents’ well-being were identified as important by care home residents and their families as part of engagement activities we have undertaken.

However factors, such as staffing, safety concerns and having appropriate clothing can impact on whether residents have opportunities to go outside (van den Berg et al., 2020).

Research on mobility in care homes has tended to focus on walking, physical activity and activities of daily living within the care home environment. There is limited research on broader concepts of mobility and life-space outside of the care home environment.

This mixed methods project aims to co-develop and co-design an intervention to improve life space mobility amongst care home residents and test for feasibility and acceptability.