Impact of APOE genotype and age on large-scale MTL neurocognitive networks

Lissaman, Rikki 2021. Impact of APOE genotype and age on large-scale MTL neurocognitive networks. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Research on medial temporal lobe (MTL) function converges on the notion that the hippocampus and perirhinal cortex (PRC) are specialised for different types of representational content: scenes and objects. The evolutionary accretion model advances this further, proposing that these MTL structures constitute key nodes within the extended hippocampal navigation and feature networks, respectively. The former network is considered more vulnerable to the impact of age and age-related neurodegenerative disease, including Alzheimer’s disease (AD). Additionally, young carriers of the apolipoprotein E (APOE) ε4 allele – an AD risk factor – have been shown to exhibit alterations within this network, supporting lifespan accounts of cognitive decline. Recently, however, this network-selective vulnerability has been challenged by reports of object-related impairments in ageing and AD risk. This thesis therefore investigated the impact of APOE genotype – especially APOE ε4 – and age on these two neurocognitive networks and their representations. To achieve this, web-based cognitive testing (Chapter 2), magnetic resonance imaging (MRI)-based structural covariance analysis (Chapter 3), and diffusion MRI-based tractography (Chapter 4) were used. In middle-aged and older adults, APOE ε4 and APOE ε2 – a risk-reducing allele – were associated with divergent age trends in perceptual discrimination independent of condition (Chapter 2). Conversely, in a sample spanning the adult lifespan, age and gender/sex – but not APOE ε4 – were associated with the structural covariance of the hippocampus and PRC (Chapter 3). Finally, in younger adults, APOE ε4 impacted the lateralisation of inferior longitudinal fasciculus (ILF) microstructure – a key tract in the feature network (Chapter 4). The findings of this thesis provide evidence that APOE genotype and age impact aspects of these networks and their representations, but it remains challenging to interpret them collectively. Nonetheless, this research addresses pre-existing limitations, and provides a foundation for studies that could aid our understanding of age- and APOE-related impact(s) on the brain and cognition.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology
Date of First Compliant Deposit:	8 November 2021
Date of Acceptance:	8 November 2021
Last Modified:	08 Nov 2021 15:19
URI:	https://orca.cardiff.ac.uk/id/eprint/145364

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