Determinants of functional decline, multimorbidity and neurodegenerative diseases: a triangulation approach

Longer life expectancy has led to a greater number of people being at risk of functional decline and conditions such as multimorbidity or neurodegenerative disease that increase the risk of disability at older ages. The challenge from a public health perspective is to identify determinants of maintenance of functional capacity as long as possible to reduce the risk and postpone disability onset. In this context, this project aims to identify determinants of functional decline, multimorbidity, and neurodegenerative disease as well as factors involved in progression from these health conditions to death.
Data from the UK Biobank cohort will be used to examine the associations of sociodemographic, behavioural, and health-related factors with change in cognitive, physical, and sensory function over time and risk of onset of multimorbidity, neurodegenerative disease and their progression to death. In order to examine the consistency of findings in different sub-groups, these associations will also be investigated in groups defined by sociodemographic factors (age, sex, ethnicity, education) or health characteristics (obesity, hypertension, diabetes, frailty status). We will also examine the directionality (is it the exposure that influences the health outcome or the reverse?) and the biological plausibility of the associations found. Mendelian randomisation will be used to examine the causal role of exposure in health outcomes. The biological plausibility of the association will be tested by examining whether microvascular function and metabolites play a role in the identified associations.
Taken together, this project will use a comprehensive approach to allow triangulation of findings and provide robust knowledge for future evidence-based personalised prevention interventions.