Kazmi, Hiba; (2019) Late onset depression: Association with clinical and imaging indicators of prodromal Parkinson’s disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The pathology of late onset depression (LOD) is unclear, with vascular and structural abnormalities reported through the use of magnetic resonance imaging (MRI). Parkinson’s disease (PD) can be preceded by LOD several years before overt motor symptoms. Use of the Dopamine Transporter Single Photo Emission Computerised Tomography (DAT SPECT) has been approved by the Food and Drugs Administration (FDA) for imaging pre synaptic dopaminergic dysfunction; aiding diagnosis in disorders such as PD. We investigated; a) presence of early clinical features associated with PD in patients with LOD (pLOD), b) dopaminergic functioning in pLOD, c) structural and vascular pathology associated with LOD. This thesis also compared visual and semi quantitative analysis (SQA) methods when rating DAT SPECTs. When compared with healthy controls (HC) (n=30) overall, pLOD (n=36) scored significantly higher on symptoms of apathy, REM sleep behaviour disorder (RBD), sleep symptoms associated with PD and autonomic and motor dysfunction. Seven pLOD were visually rated with abnormal uptake in comparison to one HC, also confirmed by the SQA which additionally found that overall, pLOD (n=29 with a DAT SPECT) had significantly lower binding in the caudate nuclei (CN). The pLOD with visually abnormal SPECTs had significantly lower clinical scores relating to olfactory dysfunction, cognition and autonomic dysfunction compared to pLOD with normal SPECTs. There were no significant group differences in structural or vascular pathology. There were significant correlations between age and left and right hippocampi (HIPP) and amygdala (AMY) and global white matter (WM) and grey matter (GM) volumes in pLOD (n=28 with an MRI). Overall, in controls (n=25), age and gender correlated with global WM. Severity of depression was not associated with regional volumes. An audit of the correct use of clinical indications for the DAT SPECT at an NHS trust confirmed correct use in all cases (n=74) and a comparison of visual and SQA methods when rating DAT SPECTS in clinical cases also confirmed very good agreement between methods.

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