Psychiatry - Theses

Permanent URI for this collection

Search Results

Now showing 1 - 1 of 1
  • Item
    Thumbnail Image
    Memory decline and Aβ amyloid as markers of neurodegeneration in preclinical Alzheimer's disease
    Lim, Yen Ying ( 2013)
    Alzheimer’s disease (AD) is pathologically characterised by neurofibrillary tangles and beta-amyloid (Aβ) plaques. Clinically, it is characterised by a gradual decline in cognitive function, particularly in episodic memory. Current neuropsychological models emphasise the measurement of cognitive impairment to determine cognitive abnormality. However, as AD is a neurodegenerative disease, it has been suggested that the repeated assessment of cognitive function could provide important information about an individual’s performance over time, particularly as any changes in cognitive function in the very early stages of the disease are likely to be subtle. The overarching aim of this thesis was to investigate the relationship between a known marker of AD, Aβ amyloid, as determined by positron emission tomography (PET) neuroimaging using 11C-Pittsburgh Compound B, and decline in cognitive function as potential markers of neurodegeneration in the preclinical stages of AD. Additionally, the role of genetic polymorphisms in modifying the relationship between Aβ amyloid and cognitive decline were explored. First, the nature and magnitude of Aβ amyloid-related impairment in cognitive function was characterised cross-sectionally in both healthy older adults and adults with mild cognitive impairment (MCI). The data suggested that there were very small differences between healthy older adults with high and low levels of Aβ amyloid. Further, in adults with MCI, high Aβ amyloid was associated with a more focal impairment in episodic memory, but low Aβ amyloid was associated with additional impairments in executive function, attention and language, suggesting the presence of other underlying neurological or psychiatric processes. The relationship between Aβ amyloid and cognitive function in both healthy older adults and adults with MCI became clearer when studied prospectively. High levels of Aβ amyloid were associated with increased rates of cognitive decline, particularly in episodic memory, and this decline occurred at the same rate in both healthy older adults and in adults with MCI. High Aβ amyloid levels were also associated with higher risk of disease progression in both healthy older adults and adults with MCI. Carriage of the apolipoprotein E (APOE) ε4 allele did not moderate this relationship between Aβ amyloid and cognitive decline; although carriage of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele did. Low levels of Aβ amyloid were associated with stable cognitive function in both healthy older adults and adults with MCI, lending strength to the hypothesis that the underlying pathological process in adults with MCI and low Aβ amyloid is non-AD in nature. These findings have important implications for future clinical trials in AD as the data strongly suggest that healthy older adults with high levels of Aβ amyloid and objectively defined decline in memory are in the preclinical stages of AD, and are promising candidates for anti-amyloid therapies aimed at halting or modifying the neurodegenerative disease process in the early stages of the disease.