Apolipoprotein e4 influences on scene representation in young adults

Episodic memory for past and future events, scene imagination, visual scene perception, and navigation, are all supported by a set of brain regions in the medial temporal lobe (MTL)and posteromedial cortex (PMC). It has been proposed that the construction of scenes, also supported by these brain regions, may provide a scaffold which underpins these many related cognitive processes. Consistent with pathology in the MTL and PMC, Alzheimer's patients are impaired in many of these cognitive processes, including scene construction. APOE e4 is the strongest known genetic risk factor for the development of late onset Alzheimer's Disease. Alterations in brain activity have been found in young adult APOE e4 carriers during scene perception and episodic memory tasks, with however, cognitive performance matched across groups. This thesis combined behavioural, genetic and imaging approaches in order to answer an overarching question: do young adult (age ~20 years) APOE e4 carriers show early behavioural (Chapters 2 and 3) and brain alterations (Chapter 4), compared to non-carriers, on sensitive cognitive paradigms assessing scene representation ability? Chapter 2 and 3 of this thesis did not detect a significant difference between APOE e4 carriers and non-carriers in overall scene representations. However, APOE e4 carriers were found to describe fewer sensory details about their imagined scenes, suggesting that subtle differences between groups may exist, but subjective experience may not be a sensitive method to detect these. In a further computerised perceptual illusion task, APOE e4 carriers showed a (non-significant) attenuation of the illusionary effect, reflecting alterations in scene representation required for strength of the illusion. Finally, I used ASL imaging (Chapter 4) to investigate scene-selective alterations in APOE e4 carriers during a visual perception task. This study failed to find a significant scene-selective functional difference between APOE e4 carriers and non-carriers, but confirmed that further work is needed to understand BOLD response alterations in young APOE e4 carriers. The findings of this thesis pave the way for further investigation to understand functional brain changes in young APOE e4 carriers, which aligned to a specific cognitive hallmark of AD, could provide a marker for increased genetic risk, but further, could help us to better understand the influence of genetic risk on brain health