Experiences of adversity and risk of dementia

Adverse childhood experience (ACE) is a term pertaining to adverse or traumatic events during childhood. These usually include experiences of abuse, household dysfunction, residential care, and victimization. Acting as a potent chronic stressor, ACEs may affect the mind and body during critical periods of development resulting in lifelong impacts.

There is growing evidence to suggest that ACEs are associated with numerous health conditions. ACEs appear to be associated with increased risk of Alzheimer's disease and have been associated with many dementia risk factors, which could potentially reflect mediating pathways. However, little is known about how the association between ACEs and dementia develops, or what factors fall on the causal pathway. Additionally, numerous dementia risk factors have been shown to interact with genetic risk for dementia. However, to our knowledge this is yet to be investigated with regard to ACEs.

Most research regarding dementia and traumatic experiences focusses on those that occur during childhood. However, psychological distress in midlife has also been shown to increase dementia risk. Additional research is required to establish whether traumatic experiences in adulthood also influence risk of dementia.

This project aims to investigate the role of ACEs as a dementia risk factor, identifying mediating factors and considering the interplay with genetic risk. Additionally, we shall consider adversity beyond childhood to consider the role of trauma later in life.

To identify potential mediators of the relationship between adverse experiences and dementia, a systematic review will be completed to synthesize existing research on the association between adverse experiences and dementia risk factors. This review shall focus on social and mental health factors, including depression, education, and social isolation.

Following this, we shall use UK Biobank data to investigate associations between adverse life experiences and dementia risk. Analysis will look at individual measures of adversity to determine whether particular experiences are associated with increased risk. The analysis will be repeated using a composite measure of adverse experiences to see if an accumulation of these negative experiences results in a larger association with dementia. Within this work, we shall consider an interaction by APOE-e4 group to establish whether there is an interplay between adverse experience and genetic risk.

To develop a greater understanding of how adverse experiences associate with dementia, a causal mediation analysis shall be conducted. Mediators considered shall be driven by the results of the systematic review.

Through this work, we hope to establish how traumatic experiences throughout life influence dementia risk. We aim to develop a greater understanding of how adverse experiences earlier in life translate to poor life brain health in later life. Identification of mediating factors could enable points for intervention, potentially attenuating associations amongst those who had experienced trauma.

Risks associated with this project include a lack of statistical power within analysis. Both dementia incidence and adverse experiences are relatively uncommon in the UK Biobank dataset. To overcome this, I will consider the use of proxy measures including fluid intelligence.