Lewy Body Dementia and the Role of Inflammation
University of Cambridge
Doctor of Philosophy (PhD)
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Surendranathan, A. (2018). Lewy Body Dementia and the Role of Inflammation (Doctoral thesis). https://doi.org/10.17863/CAM.30607
Background: Lewy body dementia (LBD), consisting of Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), is known to make up more than 15% of dementia cases at autopsy, however the clinical prevalence rate is reported to be much lower at around 5-6%. Difficulties with diagnosis and/or lack of specific treatments may contribute to this difference. This study investigated the diagnosis and management pathways of LBD and whether inflammation could play a role in the pathophysiology and hence provide a route for future diagnostic and treatment pathways. Methods: Clinical diagnostic rates of LBD in clinics across several NHS trusts in East Anglia were reviewed, followed by an in-depth notes review of patients identified with LBD together with age and gender matched controls. A literature review of the current evidence for inflammation in LBD, preceded a case control study to investigate further. Nineteen DLB patients together with 16 age and gender matched healthy controls underwent [11C]PK11195 PET imaging, and the same cohorts, plus an additional 10 matched control subjects underwent peripheral cytokine analysis. Results: The clinical prevalence rate of LBD was low compared to the known pathology rates, with delays identified in the diagnosis of DLB compared to other dementia subtypes. Delays were also seen between the onset of dementia symptoms and the clinical diagnosis of dementia in Parkinson’s disease (PD). The literature review identified studies providing evidence of inflammation in PD but few studies had been carried out in DLB. PET imaging revealed microglial activation negatively correlated with disease severity in DLB, suggesting inflammation occurs early in the disease. DLB patients also showed evidence of differences in cytokine levels compared to healthy controls. Conclusion: The study showed evidence of inflammatory changes in DLB, providing a potential target for treatment and/or biomarkers, that could assist in increasing clinical diagnostic rates.
Lewy Body Dementia, Inflammation, PET Imaging, Cytokines, Diagnosis
Some of the work (chapters 2 & 3) was carried out as part of the Diamond Lewy study, funded by the NIHR (Grant Reference Number DTC-RP-PG-0311-12001). The work described in Chapter 6 was primarily funded by the National Institute for Health Research Cambridge Biomedical Research Centre (NIHR, RG64473), Alzheimer’s Research UK and the Bury Free Press (Liffe Media Publishing Limited).
This record's DOI: https://doi.org/10.17863/CAM.30607
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