Motor functioning strongly impacts the ability to maintain functional independence, in particular among the elderly. The detrimental influence of motor impairments on functional independence is painfully noticeable in individuals with neurodegenerative movement disorders, in particular in those with the most widely recognized among these disorders: Parkinson’s Disease (PD). As the number of elderly individuals is expected to grow due to ageing of populations worldwide, there is now a growing sense of urgency to unravel determinants of motor functioning and PD. This thesis provides novel insight on determinants of motor functioning and PD.
Intriguingly, deterioration of motor functioning begins well before individuals are clinically diagnosed with PD, as a result of accumulating pathology in the brain, in the ‘prediagnostic’ phase of the disease. This thesis describes the identification of risk factors (both genetic and non-genetic) and prodromal features of PD, which adds to our understanding of the prediagnostic phase of PD. Furthermore, this thesis examines modalities to identify individuals at high risk of PD.
Progressive motor impairments may also occur in the prediagnostic phase of other neurodegenerative diseases than PD, including those that are primarily characterized by dementia. Motor impairments are often accompanied by cognitive deficits across neurodegenerative diseases, typically adding to the loss of functional independence. This thesis seeks to fill the gap on knowledge on overlap of cognitive and motor impairments in the prediagnostic phase of neurodegenerative diseases and on overlap in their lifetime risk by presenting observational data from the general population. Taken together, these observations add to our understanding of determinants of motor impairments, which has implications not only for PD but also for other neurodegenerative diseases.
This thesis concludes by placing its main observations in a broader clinical context, pointing out methodological considerations that merit attention in the interpretation of these observations, and offering directions for future research.

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M.A. Ikram (Arfan) , P.J. Koudstaal (Peter) , M.K. Ikram (Kamran)
Erasmus University Rotterdam
hdl.handle.net/1765/116600
Department of Neurology

Darweesh, S. (2019, May 29). Motor Functioning and Parkinson’s Disease: Insights from the general population. Retrieved from http://hdl.handle.net/1765/116600