Medicine (RMH) - Theses
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ItemMedication use of anti-cholesterol drugs and cognitive decline in ageing( 2022-08)Projections estimate 131.5 million will be living with dementia by the year 2050. Alzheimer’s disease is the leading cause of dementia, accounting for about two-thirds of all cases and is a global public health priority. Alzheimer’s disease risk escalates with age and lacks efficacious drugs. Statins are prescribed to lower cholesterol levels and the risk of adverse cardiovascular events. Some epidemiological studies have linked statin use to improved cognitive functioning. Nonetheless, literature in this field is conflicting. Thus, investigations of long-term statin use from midlife have been suggested in recent systematic reviews. To the best of our knowledge, only one study has examined a female-specific cohort, and only few studies have investigated this relationship over a period of at least ten years, and prior to this thesis, no study has examined this relationship in women over a 24-year period. Chapters 1 and 2 examined the current literature regarding statin-cognition relationship. Previous systematic review suggests a mixed and inconclusive relationship between statins and cognitive outcome: however, this thesis provided the first evidence of this relationship extending to the prodromal phase of neuropathological change. A comprehensive systematic review and meta-analysis into statin and cognition found that the significant difference reported in the current statin studies was mainly driven by male statin users. This review highlighted the importance of having long-term statin studies and the urgent need to focus on female statin users. Chapter 4 presented a cross-sectional analysis of the relationship between statin and cognition in participants of the Women’s Healthy Ageing Project. Independent of underlying vascular risk, current statin users, initiation of statin use by women (1-4 years of use) was associated with the greatest deterioration in global cognitive function. This effect is not simply reflective of the lipid levels in the women. Chapters 5 and 6 investigated the longitudinal effect of statin consumption on the cognition of Australian ageing women over time. Participants from the longitudinal Women’s Healthy Ageing Project completed assessments from 1992 to 2016. Statin use by women was associated with greatest decline in episodic memory, global cognitive function and visuospatial ability. Non-statin users were also mostly seen to have a better cognition than statin users across this 24-year period. Type of statins do appear important and the effect of statins on cognition could take up to many years before it is noticeable, highlighting the importance of needing an extensive duration (more than 20 years) of longitudinal studies. This thesis presented the first systematic review and meta-analysis in highlighting the paucity of statin studies with long duration and lack of inclusion of female participants, who are at a much greater risk than their male counterparts. This thesis was the first to examine this relationship in a female only cohort in more than 20 years of follow-up. The results of this thesis, in concert with previous literature, suggest statin has a substantial role in jeopardizing our cognition and the detrimental effects of statins could take many years to be apparent. However; it is clear that the complex connection between statin and brain health requires further research to elucidate the underlying mechanism governing this relationship.
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ItemBiological assessment of geriatric rehabilitation inpatients( 2022)Chronological age is a major risk factor for the development of chronic diseases and frailty. The growing ageing population has imposed a heavy burden on healthcare systems which are being inundated with geriatric patients. In clinical practice, older adults are assessed and managed by the Comprehensive Geriatric Assessment (CGA), a multidimensional and interdisciplinary clinical tool that evaluates medical conditions and functional capacity in multiple domains. While the CGA contains several detailed clinical tools, it currently does not involve any biological assessment. A biological assessment could identify individuals with an accelerated ageing process, provide additional information about their health status and ultimately help early diagnosis, prevention and recovery of age-related diseases. This PhD project investigated the biological determinants of adverse health outcomes in geriatric rehabilitation inpatients using clinical pathology data. The unresolved inflammation characterized by high C-reactive protein and low albumin, vitamin D deficiency and higher biological age determined by combined blood biochemistry markers were associated with frailty, institutionalization and mortality. In addition, a literature review that encompasses cell cycle regulators as cellular senescence markers in human peripheral blood cells was conducted, showing the potential as a biological assessment clinically. This thesis highlighted the predictive value of pathology parameters for adverse health outcomes and the importance of ensuring the resolution of inflammation and adequate levels of vitamin D during geriatric rehabilitation. Future studies are required to investigate the association of senescence burden in blood samples with clinical phenotype and rehabilitation outcomes, and evaluate the utility of CGA integrated with biological assessments in care planning.