Brain health in ageing and Parkinson's disease
Age-related decline in brain health appears to be inevitable to some extent. In some people, ageing is also associated with additional burden of neurodegenerative diseases, such as Parkinson’s disease (PD). However, distinguishing between normal and pathological ageing trajectories is complicated, a...
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| Format: | Thesis |
| Language: | English |
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2021
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| _version_ | 1797107645769842688 |
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| author | Nobis, L |
| author2 | MacKay, C |
| author_facet | MacKay, C Nobis, L |
| author_sort | Nobis, L |
| collection | OXFORD |
| description | Age-related decline in brain health appears to be inevitable to some extent. In some people, ageing is also associated with additional burden of neurodegenerative diseases, such as Parkinson’s disease (PD). However, distinguishing between normal and pathological ageing trajectories is complicated, as neither are well characterised. This thesis quantifies effects of normal and pathological ageing on mood, motivation, and brain structure, with a focus on PD.
In the first part of the thesis, I estimate general effects of healthy ageing on mood and brain structure. I address whether mood generally improves or whether age-related changes to the brain increase risk for mood disorders. I calculate trajectories of grey matter atrophy, and present norm values for one of the most vulnerable brain areas in ageing, the hippocampus. In the second part of the thesis, I investigate how PD affects mood, motivation, and brain structure differently from healthy ageing. Debilitating mood symptoms like apathy and depression are often reported in PD, but it is unclear whether they might be secondary to the disability that patients live with, or a direct result of PD-related pathology. This is tested formally by analysing prevalence of these symptoms and taking into account levels of disability, as well as by investigating effects of serotonergic modulation on affective processing and decision-making. Finally, I evaluate whether these potential differences in PD can be linked to brain structure.
The results demonstrate that normal ageing is on average more likely to be associated with improvements in mood. In contrast, PD was linked to higher rates of neuropsychiatric symptoms, even when accounting for levels of disability. This supports the hypothesis that neuropsychiatric symptoms in PD are primarily the result of PD-related brain pathology, rather than due to secondary effects. Serotonergic modulation during behavioural testing further revealed a role for serotonin in apathy that may depend on levels of baseline intrinsic motivation. Finally, while healthy ageing is associated with strong declines in volume in almost all areas of the brain, no robust specific effects of PD on brain structure were found. Together, this work contributes to the search for MRI-based biomarkers of neurodegeneration, as well as the understanding of mood disorders in Parkinson’s disease. |
| first_indexed | 2024-03-07T07:17:27Z |
| format | Thesis |
| id | oxford-uuid:dd97dd96-adcb-43d1-b58e-0c6be170d098 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:17:27Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:dd97dd96-adcb-43d1-b58e-0c6be170d0982022-08-25T08:53:10ZBrain health in ageing and Parkinson's diseaseThesishttp://purl.org/coar/resource_type/c_db06uuid:dd97dd96-adcb-43d1-b58e-0c6be170d098EnglishHyrax Deposit2021Nobis, LMacKay, CHusain, MAge-related decline in brain health appears to be inevitable to some extent. In some people, ageing is also associated with additional burden of neurodegenerative diseases, such as Parkinson’s disease (PD). However, distinguishing between normal and pathological ageing trajectories is complicated, as neither are well characterised. This thesis quantifies effects of normal and pathological ageing on mood, motivation, and brain structure, with a focus on PD. In the first part of the thesis, I estimate general effects of healthy ageing on mood and brain structure. I address whether mood generally improves or whether age-related changes to the brain increase risk for mood disorders. I calculate trajectories of grey matter atrophy, and present norm values for one of the most vulnerable brain areas in ageing, the hippocampus. In the second part of the thesis, I investigate how PD affects mood, motivation, and brain structure differently from healthy ageing. Debilitating mood symptoms like apathy and depression are often reported in PD, but it is unclear whether they might be secondary to the disability that patients live with, or a direct result of PD-related pathology. This is tested formally by analysing prevalence of these symptoms and taking into account levels of disability, as well as by investigating effects of serotonergic modulation on affective processing and decision-making. Finally, I evaluate whether these potential differences in PD can be linked to brain structure. The results demonstrate that normal ageing is on average more likely to be associated with improvements in mood. In contrast, PD was linked to higher rates of neuropsychiatric symptoms, even when accounting for levels of disability. This supports the hypothesis that neuropsychiatric symptoms in PD are primarily the result of PD-related brain pathology, rather than due to secondary effects. Serotonergic modulation during behavioural testing further revealed a role for serotonin in apathy that may depend on levels of baseline intrinsic motivation. Finally, while healthy ageing is associated with strong declines in volume in almost all areas of the brain, no robust specific effects of PD on brain structure were found. Together, this work contributes to the search for MRI-based biomarkers of neurodegeneration, as well as the understanding of mood disorders in Parkinson’s disease. |
| spellingShingle | Nobis, L Brain health in ageing and Parkinson's disease |
| title | Brain health in ageing and Parkinson's disease |
| title_full | Brain health in ageing and Parkinson's disease |
| title_fullStr | Brain health in ageing and Parkinson's disease |
| title_full_unstemmed | Brain health in ageing and Parkinson's disease |
| title_short | Brain health in ageing and Parkinson's disease |
| title_sort | brain health in ageing and parkinson s disease |
| work_keys_str_mv | AT nobisl brainhealthinageingandparkinsonsdisease |