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Title: Olfaction in Parkinson's Disease
Author: Silveira Moriyama, L.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2009
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This thesis examines the clinical and pathological involvement of the olfactory system in Parkinson’s Disease (PD). The main aim is to investigate the practical use of smell identification tests (SITs) in parkinsonism and tremor. A secondary objective is to investigate the pathological involvement of the rhinencephalon. Commercially available SITs were used to differentiate PD patients from control subjects in the UK, Brazil and Sri Lanka, showing SITs have combinations of sensitivity and specificity greater than 80%. Based on the data obtained a traffic light ruler was devised to determine the likelihood of a patient having PD at the time of the initial consultation. This was then used to interpret SITs in 34 patients with possible parkinsonism, showing 86.4% sensitivity and 80.0% specificity of SITs when compared to dopamine transporter imaging using single photon emission computed tomography (SPECT) as the gold-standard for detecting nigrostriatal dopamine denervation. Olfaction was shown to be severely impaired in parkinsonism related to LRRK2 mutations, moderately impaired in subjects with pure autonomic failure, multiple system atrophy and progressive supranuclear palsy (PSP) and normal in patients with essential tremor, dystonia and in subjects who had been diagnosed as having PD, but were found to have normal scans. This indicates that SITs will be more useful in differentiating PD from non-degenerative tremors than from atypical parkinsonism. Neuropathological changes were investigated in the rhinencephalon and it was demonstrated that α-synuclein accumulation in the primary olfactory cortex is heterogeneous, being more severe in the temporal subdivision of the piriform cortex. The piriform cortex had Lewy body pathology in all 10 PD cases studied, as well as in 7 control cases who presented incidental Lewy body pathology and four cases of LRRK2 related parkinsonism. The piriform cortex had abnormal tau accumulation in 6 PSP patients, suggesting tauopathy in the rhinencephalon is a possible substrate for hyposmia in PSP.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available