There is sufficient evidence that a neurodegenerative process in Parkinson’s Disease (PD) starts many years before the clinical diagnosis. The progression of PD is generally slow and, because it is diagnosed based on established motor features, it is probable that subtle motor manifestations appear in the pre-diagnostic phase of PD. Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a condition known to be part of the prodromal phase of PD. The PREDICT-PD study is a population-based cohort which aims to identify individuals at risk of PD based on the presence and absence of risk factors. The first project of this thesis investigated the association between first presentation of motor symptoms (tremor, rigidity and balance difficulties) and subsequent PD in a large primary care dataset in East London, including almost 3 decades of clinical information from over a million individuals. People who went on to develop PD reported motor symptoms up to 10 years before PD diagnosis. Tremor had the highest association with future PD followed by balance difficulties and rigidity. The second project aimed to identify the range of motor features in the elderly population participating in the PREDICT-PD cohort study and document their rate of progression over time. People classified as having a higher risk of future PD (using the PREDICT-PD algorithm) were more likely to have early parkinsonian signs than the lower risk group. Six years later, they also showed a bigger motor decline compared with people in the lower risk group. The third project was focused on developing two new objective motor tools, the Distal Finger Tapping test and the Slow-Motion Analysis of Repetitive Tapping. Both tests were able to detect abnormal patterns of movement amongst people with early PD. Finally, a motor battery was created and implemented in a group of patients with iRBD. A higher proportion of patients with iRBD had early parkinsonian signs compared with controls. The motor battery was able to detect early patterns of motor dysfunction not captured by standardised clinical scales. The work presented in this thesis demonstrates that motor features start in the pre-diagnostic phase of PD and describes new motor signatures in the prodromal phase of PD
