Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by motor dysfunctions because of death of dopaminergic cells in the basal ganglia (BG). It is usually treated with the dopamine precursor levodopa and/or deep brain stimulation (DBS) where electrical stimulus pulses are delivered to parts of the BG.

Despite much research into potential biomarkers, current diagnosis and disease staging remains reliant on the clinical assessment of motor symptoms using rating scales. This causes several problems: assessments are subject to inter-observer variability; rating scales are nonlinear; and the scales only enter their working range once more than half of the dopamine producing cells in the brain have died.

New treatments, and in particular disease modifying drugs (DMDs), are desperately needed. Only around one in 10 newly developed drugs survives rigorous assessment in trials, which are both time consuming and very costly. Failures must be recognised quickly so that resources can be transferred to the next candidate agent. When evaluating DMDs investigators are looking for small changes in disease trajectory. The more sensitive a biomarker, and the less affected it is by noise, the sooner a difference will be seen after treatment commences. A sensitive and noise resistant measure is therefore critical to minimising resource consumption in the evaluation of doomed drugs. An additional problem arises when the measurement is affected by background symptomatic medication, which the great majority of PD patients are treated with. Symptomatic treatment can obscure progression in motor scales almost completely, rendering them completely insensitive to changes in disease trajectory.

Thanks to novel technology we are now able to quantify motor disturbances rapidly, accurately, non-invasively, and objectively using wearable sensors. Due to its portable and easily operable nature, wearable sensors are replacing motion detection systems and force plates to give quick clinical measurements. This thesis examines the usefulness of precise measurements of gait and balance as a means of quantifying PD. The aim is to identify and characterise features that change significantly over periods of months rather than years., are not noisy, and are relatively unaffected by the presence of symptomatic medication. Gait measurements will be taken from both PD patients and age-matched controls every three months for two years. In addition, cross-sectional studies will be conducted to examine gait in patients’ on- and off- medication and DBS states to allow rapid evaluation of which features show the greatest change and thus warrant the examination from inducing abrupt shifts in parkinsonian state.