Gallagher, DA; (2013) Non-motor and neuropsychiatric features of Parkinson's disease. Doctoral thesis , UCL (University College London).

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Abstract

This thesis focuses on non-motor symptoms (NMS) of Parkinson’s disease (PD), particularly the neuropsychiatric symptoms of visual hallucinations, apathy and impulse control disorders. A clinical cohort study and pathology study were performed. PD patients (N=94) were recruited and each underwent neurological examination for motor aspects of the disease, detailed multi-domain cognitive assessment including executive and visuoperceptive function, and a battery of validated non-motor assessments for symptoms including mood, apathy, sleep, fatigue, psychosis, autonomic function, disability and health-related quality of life (QOL). A subgroup (N=50) also had detailed ophthalmological examination. In the autopsy study, the presence of ante-mortem visual hallucinations (VH) in PD donors was correlated with Lewy body (LB) density and distribution at different cortical locations. The clinical study examined the impact of NMS on QOL and found that NMS, particularly depression, had stronger association with QOL than motor scores, but despite this NMS were often under-reported by their treating neurologist. A significant proportion of pathologically confirmed PD patients presented exclusively with NMS and this led to misdiagnosis and, in some cases, inappropriate investigations and treatment. An aetiological model of VH was proposed and examined; factors investigated included dopaminergic medication, higher cortical function, sleep and ophthalmic pathology. Clinical associations of VH were rapid eye movement sleep behaviour disorder, autonomic function, and executive and visuoperceptive cortical function. There was however no clear association with co-existing ophthalmic pathology. In the post-mortem analysis, LB involvement at corresponding cortical areas was confirmed, including frontal (executive) and temporal and trans-entorhinal (visuoperception) cortices. A meta-analysis of studies reporting pathological gambling was performed and an association with dopaminergic medication, particularly dopamine agonist therapy, and co-existing psychopathology was confirmed.

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