An integrated epidemiological approach to understanding the relationship between lung health and multi-morbidity

The UK spends 70% of its healthcare budget caring for patients with multiple long-term health conditions such as dementia and chronic obstructive pulmonary disease (COPD); driven by aging populations and lifestyle factors, this figure is expected to rise. Chronic lung disease and dementia are therefore key global health challenges.

Cognition describes mental abilities, such as thinking, problem solving and remembering. Problems with cognition (cognitive dysfunction) can lead to dementia and appear very common in people with chronic lung disease. Although cognitive dysfunction may be mild and unnoticed at first, it may gradually make it more difficult for patients to perform their daily activities including taking medicines correctly. Cognitive dysfunction in chronic lung disease eventually leads to worse health, more time in hospital and shorter survival.

Individuals with chronic lung disease may be at increased risk of mild cognitive impairment (MCI) and dementia due to a combination of factors, which are both more frequent among those with lung disease and known to negatively impact on cognition (e.g., smoking and high blood pressure) or as a direct result of lung disease (e.g., low oxygen levels). However, there does seem to be a consistent link between cognitive impairment and lung disease independent of these shared factors, suggesting mechanisms specific to respiratory limitation.

The aim of this project is to determine whether chronic lung disease and cognitive impairment share a common causal pathway. It will do this by bringing together interdisciplinary expertise in epidemiology and statistics, to understand the complex interaction between genetic, developmental and early life events which determine lung health and cognition (MRC strategic aim 4).

It will also explore the relationship between early life cognition, co-morbidity and lung function trajectories using a population-based life course perspective applied to the Avon Longitudinal Study of Parents And Children (ALSPAC) cohort. (MRC strategic aim 1).

The objectives are:
a) Apply integrated genetic epidemiological methods developed by our team (2 sample Mendelian Randomisation) from large European populations to determine the causal association between lung function, cognitive impairment and risk of dementia
b) Determine if early life changes in lung function are associated with cognitive dysfunction and multi-morbidity using existing data from the ALSPAC cohort.

Benefits and applications are:
1) Help to identify modifiable risk factors and potential therapeutic targets to reduce the risk of developing dementia.

2) Advance our understanding behind the mechanisms of cognitive dysfunction in chronic lung disease.

3) Initiate the development of new ways to detect, prevent or delay progression of cognitive dysfunction in at risk populations. This will help patients to manage their treatment, maintain their health and keep out of hospital. It could also prolong survival.

4) Increase our understanding about early life risk factors for chronic lung disease and multi-morbidity

5) Inform public health policy through engagement with organisations responsible for health services delivery and management of two major long-term conditions, Chronic Obstructive Pulmonary Disease (COPD) and Dementia.
a. Awareness of cognitive dysfunction & multi-morbidity
b. Inform self-management and education
c. Keeping people with COPD and Dementia healthy at home

6) Inform and open new research questions about the interaction between long-term conditions and lung health such as cardiovascular disease, depression and diabetes.

The WHO estimates that dementia will affect 80 million people in 20 years, so there is an urgent need to identify modifiable risk factors. Mild cognitive impairment is associated with a 5-10% annual conversion rate to dementia but is considered a potentially reversible state.
3 million people live with COPD in the UK, the majority have two or more long-term health conditions, it is therefore a disease of 'multi-morbidity'. (MRC strategic theme 'living a long and healthy life')
The majority of observational studies provide evidence for an independent association between lung function and cognitive impairment. However a number of unmeasured or unaccounted confounders are likely to bias this relationship.
Objectives & Methods
Part 1: Two-sample Mendelian Randomisation using existing Genome Wide Association Studies to determine the causal association between lung function, cognitive impairment and risk of dementia
Mendelian Randomization (MR) is a form of analysis that uses genetic variants as instrumental variables. Using summary data from GWAS consortia in two-sample MR increases statistical power, particularly in relation to testing effects on binary disease outcomes, such as Alzheimer's Disease (AD) or Cognitive Impairment (CI).
Part 2: Determine if early life course lung function trajectories are associated with cognitive dysfunction and multi-morbidity using existing longitudinal data from the ALSPAC cohort.
Several measures of functional cognition and comorbidity are available from the ALSPAC clinic at 24 years. Four FEV1 trajectories from childhood to early adulthood were identified in using latent profile modelling: persistently high (4%), normal (45%), below average (44%), and persistently low (7%).
Setting the normal FEV1 trajectory as the baseline group, we will use multinomial logistic regression model to investigate the risk (betas & 95%CIs) of the membership of other trajectories per unit increase of a continuous measure of functional cognition.

This research project has the potential for far reaching impact. It aims to help identify modifiable risk factors and potential treatments to reduce the risk of developing dementia and advance our understanding of the mechanisms that cause cognitive dysfunction and multi-morbidity in chronic lung disease.
Ultimately this should allow development of new ways to detect, prevent or delay progression of cognitive dysfunction in chronic lung disease, thereby helping patients to manage their treatment, maintain their health and keep out of hospital. It could also prolong survival.

National & International policy makers:
There will be policy implications relating to findings that may lead to improved recognition or enhanced screening for dementia and multi-morbidity in high-risk populations (such as those with chronic lung disease). In addition this could lead to improved healthcare advice and public health interventions to lessen the risk of adverse outcomes. Although these are likely to include tobacco control and cardiovascular risk reduction there are other modifiable factors of potential importance, including diet, obesity and physical activity that are not currently recognised as adverse factors for future lung health.

Health Professionals & Commissioners:
Clinicians including GPs, specialists in respiratory & elderly medicine, and memory clinics will benefit from an increased awareness and understanding about early life risk factors for chronic lung disease and multi-morbidity and dementia.
It also has implications for the organisation of health services delivery. Specifically, these include regional clinical commissioning groups (CCG) and NHS England who are working on sustainability and transformations plans (STPs) in key themes of respiratory, dementia and long-term conditions such as COPD and Dementia.
This work on cognition and co-morbidity in chronic lung disease will also benefit front line clinical staff to develop new ways of supporting people with COPD to self-manage and deliver effective education.

Charities and research funding bodies:
This project addresses the key global health challenges highlighted by the NIHR, MRC and British Lung Foundation. It will allow these funding bodies to prioritise and allocate resources appropriately for future research and improve communications and support for patients and carers who may be affected by chronic lung disease and dementia.

The general public:
3 million people live with COPD in the UK but only 1 million have been diagnosed, meaning many miss out on the opportunity for the help and support of healthcare professionals. The wider public will benefit from a raised awareness of the increasing health challenge and implications of living longer with multiple health conditions. It will allow people to consider the lifestyle changes that they may be able to take in order to protect themselves. The findings could also be used to help people with COPD and Dementia and their carers better understand what is needed to stay healthy and manage their long terms conditions to stay in their own home

We will use 'PolicyBristol', a dedicated policy unit working with researchers to enhance the influence and impact of research from across the University of Bristol on policy and practice at the local, national and international level. On a practical level this is achieved through Policy Briefings and Reports, Events such as a policy workshop or seminar and Communications: including via social media platforms such as blogs and Twitter