Characterising brain network differences during scene perception and memory in young adult APOE-e4 carriers: multi-modal imaging in ALSPAC

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Approximately 850,000 people in the UK have dementia; by 2025, this will increase to over one million, and by 2050 is projected to exceed 2 million. The annual financial cost of neurodegenerative disease to the UK economy is over £24 billion and rising; yet delaying dementia onset by just 5 years could reduce these costs by half. The earlier that potential interventions can be implemented, therefore, the greater the benefit for improving health and the greater the opportunity to reduce the economic and societal burden of dementia. Key to knowing when and in whom to apply preventative interventions is the identification of at-risk individuals prior to the onset of age-related cognitive decline. Here, we view 'vulnerability' to poorer cognitive health in later life as not exclusively related to 'aging', but instead, to the accumulation of risks across the lifespan. This account predicts that some of the cognitive and brain differences evident in later life can be predicted by early life factors, and lends itself to the study of young healthy individuals who are at heightened risk of age-related cognitive decline via possession of genes associated with cognitive disorders of ageing. In this research proposal, we focus on the potential influence of one such common semi-dominant risk allele, APOE-e4, by asking: (a) whether healthy APOE-e4 carriers in early adulthood show selective brain and behavioural differences (compared to non-carriers) that are consistent with the early cognitive and anatomical markers of detrimental aging, and (b) how such early life effects may be moderated by cognitive reserve, gender and lifestyle factors.A large-scale neuroimaging study will be undertaken in young adults from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, including novel application of 7T MRI which allows detailed assessment of key brain structures in the medial temporal lobe (e.g., hippocampus). This approach, which is founded on strong pilot evidence for early life brain network changes in young APOE e4 carriers (particularly during scene perception and memory) will identify the circumstances under which such cognitive changes in young at-risk individuals are seen, ask whether these brain network alterations are linked to behavioural performance (e.g., successful perception and memory), and determine how this early life cognitive vulnerability may be moderated by gender, lifestyle and cognitive reserve.