Abstract
Parkinson's disease covers a wide spectrum of symptoms, ranging from early non-motor symptoms to the characteristic bradykinesia, tremor and rigidity. Although differences in the symptomatology of Parkinson's disease are increasingly recognized, there is still a lack of insight into the heterogeneity of the pre-diagnostic phase of Parkinson's disease. In this perspective, we highlight three aspects regarding the role of population-based studies in providing new insights into the heterogeneity of pre-diagnostic Parkinson's disease. First we describe several specific advantages of population-based cohort studies, including the design which overcomes some common biases, the broad data collection and the high external validity. Second, we draw a parallel with the field of Alzheimer's disease to provide future directions to uncover the heterogeneity of pre-diagnostic Parkinson's disease. Finally, we anticipate on the emergence of prevention and disease-modification trials and the potential role of population-based studies herein. In the coming years, bridging gaps between study designs will be essential to make vital advances in elucidating the heterogeneity of pre-diagnostic Parkinson's disease.
Highlights
Parkinson’s disease (PD) covers a wide spectrum of symptoms, ranging from early non-motor symptoms, such as constipation, REM-sleep behavior disorder (RBD) and hyposmia [1, 2], to the characteristic motor symptoms bradykinesia, tremor and rigidity [3]
A similar appearing Parkinson syndrome can result from many different causes and even one specific cause can bring about heterogeneous symptomatology [4]
We will elaborate on lessons learned from population-based studies in the field of Alzheimer’s disease (AD) to provide future directions for understanding the diversity of risk factors and prodromal symptoms of PD
Summary
Parkinson’s disease (PD) covers a wide spectrum of symptoms, ranging from early non-motor symptoms, such as constipation, REM-sleep behavior disorder (RBD) and hyposmia [1, 2], to the characteristic motor symptoms bradykinesia, tremor and rigidity [3]. Preclinical biomarkers and prodromal symptoms in case-control studies is methodologically challenging For these type of study questions regarding pre-diagnostic PD, the design of population-based cohort studies offers several important advantages. Multiple enriched risk cohort studies are ongoing, including the Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration (TREND) study, the Parkinson Associated Risk Study (PARS), the Parkinson’s Progression Markers Initiative prodromal cohort (PPMI) and the Oxford Parkinson’s Disease Centre (OPDC), which provide insight into early phases of PD and create platforms to recruit subjects for trials [8, 11, 53] These studies include various populations with a high risk of PD, such as asymptomatic mutation carriers, people with RBD or people with composite prodromal features. Collaboration between trial initiatives and observational population-based studies is essential to make the first steps toward PD prevention
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