The greatest genetic factor in how well we age cognitively is Apolipoprotein E (APOE), a single nucleotide polymorphism with three allelic variants: epsilon-2, epsilon-3 and epsilon-4 (hereafter ε2, ε3, ε4). The ε4 allele is associated with an increased risk of cognitive disadvantage in later life, however, the effects of this variant are not isolated to old-age, with some studies reporting cognitive advantages in youth. This thesis investigates the influence of APOE ε4 on cognition from mid-adulthood, a point in the lifespan when the detrimental effects of this allele may be emerging. This thesis begins with a systematic review and meta-analysis of the literature to-date, and suggests attention may be sensitive to ε4 differences in mid-adulthood, however, effects of the allele are not consistently shown, perhaps due to methodological limitations including the use of insensitive neuropsychological batteries (Chapter 1). Next, behavioural paradigms providing a sensitive index of both selective (Chapter 2) and executive attention (Chapter 3), suggest many attentional processes are intact in mid-age (45-55 years) ε4 carriers. Subtle deficits, however, are apparent on prospective memory (PM) and Stroop-switch paradigms, indicating a goal maintenance disadvantage. In addition, a proxy of cognitive reserve was found to moderate the effects of ε4 on executive attention in mid-adulthood (Chapter 4). Follow-up research used paradigms that target the distinct processes supporting focal and non-focal PM to interrogate the profile of change observed in mid-age ε4 carriers, identifying a profile of disadvantage consistent with that observed in pathological ageing (Chapter 5). PM, however, was not found to differentiate ε4 carriers in older individuals at heightened risk of converting to dementia (Chapter 6). Collectively, this research provides evidence for a profile of accelerated ageing in ε4 carriers, with subtle disadvantages apparent in executive attention by the end of the 5th decade.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:737647 |
| Date | January 2018 |
| Creators | Lancaster, Claire |
| Publisher | University of Sussex |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://sro.sussex.ac.uk/id/eprint/73536/ |
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