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Abstract
Inflammation plays important roles in ageing and neurodegenerative diseases. Although studies have shown the association of increased inflammatory markers with brain structural and functional degeneration in ageing, the implication for clinical practice is often restricted by the examination of selected inflammatory markers and inconsistent findings across different studies. This Ph.D. thesis aims to examine the impacts of inflammation on ageing brains in community-based older individuals aged 70-90 years, using multimodal MRI data.
In order to assess how inflammation associates with ageing brains, I first examined age-related brain structural changes over two years in the study sample. The findings showed widespread atrophy across brain grey (GM) and white matter (WM), which is comparable to previous longitudinal studies in similar age range.
Next, all inflammatory markers available to the study sample (n = 11) were examined for their associations with brain structural indices. The results showed that higher macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels were associated with lower GM and WM volumes. The inflammatory markers were then categorised into cytokine, acute phase and vascular factors using principal component analysis. Higher levels of the acute phase factor were associated with heavier WM hyperintensity (WMH) burdens, whereas higher levels of the vascular factor were linked to greater GM and WM atrophy.
The relationship of MIC-1/GDF15 levels with brain was then investigated in more details using multimodal MRI data in both cross-sectional and longitudinal settings. The findings indicated that higher MIC-1/GDF15 serum levels were associated with GM and WM deterioration, and decline in WM microstructural integrity. Over two years, individuals with more increase in MIC-1/GDF15 levels had greater atrophy in cortices and subcortical structures.
In conclusion, this thesis started with examining the association of eleven inflammatory markers with ageing brains, and then focused on MIC-1/GDF15 in relation to various brain structural measures. It identified an inverse relationship between MIC-1/GDF15 and integrity of the ageing brains. The findings have practical implications for using MIC-1/GDF15 as a diagnostic and therapeutic target for age-related brain degeneration.