Journal of Parkinson's disease
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Parkinson's disease (PD) is currently clinically defined by a set of cardinal motor features centred on the presence of bradykinesia and at least one additional motor symptom out of tremor, rigidity or postural instability. However, converging evidence from clinical, neuropathological, and imaging research suggests initiation of PD-specific pathology prior to appearance of these classical motor signs. ⋯ Currently, several nonmotor symptoms have been associated with an increased risk to develop PD in otherwise healthy individuals and ongoing research is aimed at validating a variety of candidate PD biomarkers based on imaging, genetic, proteomic, or metabolomic signatures, supplemented by work on tissue markers accessible to minimally invasive biopsies. In fact, the recently defined MDS research criteria for prodromal PD have included combinations of risk and prodromal markers allowing to define target populations of future disease modification trials.
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Currently, several α-synuclein immunotherapies are being tested in experimental Parkinson's disease models and in clinical trials. Recent research has revealed that α-synuclein is not just an intracellular synaptic protein but also exists extracellularly. ⋯ The revelation that α-synuclein is present outside cells has increased the interest in antibody-based therapies and opens up for the notion that microglia might play a key role in retarding Parkinson's disease progression. The objectives of this review are to describe and contrast the use of active and passive immunotherapy in treating α-synucleinopathies and highlight the likely important role of microglia in clearing misfolded α-synuclein from the extracellular space.
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Multicenter Study
Associations between Cerebrospinal Fluid Biomarkers and Cognition in Early Untreated Parkinson's Disease.
Mild cognitive impairment and dementia are common, clinically important features of Parkinson's disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments. ⋯ The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson's disease are associated with the risk of future cognitive decline and dementia.
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In the Netherlands, the largest health technology assessment (HTA) program funds mainly (cost-)effectiveness studies and implementation research. The cost-effectiveness studies are usually controlled clinical trials which simultaneously collect cost data. The success of a clinical trial typically depends on the effect size for the primary outcome, such as health gains or mortality rates. ⋯ This trial showed no effects for the primary outcome, but the ParkinsonNet concept tested in this study was nevertheless met with great enthusiasm and was rapidly implemented throughout an entire country, and meanwhile also internationally. We applied the capability approach to the ParkinsonNet concept, and this analysis yielded additional benefits within several capability domains. These findings seems to substantiate the claim that richer policy debates may ensue by applying the capability approach to clinical trial data, in addition to traditional outcomes.
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Review
An update of the impact of deep brain stimulation on non motor symptoms in Parkinson's disease.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for patients with Parkinson's disease (PD), especially those with advanced motor complications. The effect of STN DBS on non motor symptoms (NMS) of PD is less well studied. In this article, we review the pertinent literature on the impact of STN DBS on NMS when they co-exist with disabling motor symptoms in PD patients. We also present evidence that the number and the severity of most NMS decrease after STN DBS which can have a major impact on patients' quality of life.