Parkinson's disease subtypes: Lost in translation?
ABSTRACT Like many neurodegenerative disorders, Parkinson's disease (PD) is clinically highly heterogeneous. A number of studies have proposed and defined subtypes of PD based on clinical features that tend to cluster together. These subtypes present an opportunity to refine studies of aetiology, course and treatment responsiveness in PD, as clinical variability must represent underlying biological or pathophysiological differences between individuals. In this paper, we review what subtypes have been identified in PD and the validation they have undergone. We then discuss what the subtypes could tell us about the disease and how they have been incorporated into studies of aetiology, progression and treatment. Finally, with the knowledge that they have been incorporated very little into PD clinical research, we make recommendations for how subtypes should be used and make some practical recommendations to address this lack of knowledge translation.
- SourceAvailable from: Yue Huang
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- "Parkinson's disease (PD) is the most common neurodegenerative movement disorder in the elderly (approximately 2% of the population aged over 60) with an average age of onset of 60 years and a variety of different subtypes  . Patients with young disease onset often have a benign disease course and a lower rate of dementia compared to those with later disease onset , and previous studies show that genetic factors influence both the age of onset   and clinical subtypes of PD   . "
ABSTRACT: Background. í µí»¼-Synuclein (SNCA) and microtubule-associated protein tau (MAPT) are the two major genes independently, but not jointly, associated with susceptibility for Parkinson's disease (PD). The SNCA gene has recently been identified as a major modifier of age of PD onset. Whether MAPT gene synergistically influences age of onset of PD is unknown. Objective. To investigate independent and joint effects of MAPT and SNCA on PD onset age. Methods. 412 patients with PD were recruited from the Australian PD Research Network (123) and the Neurology Department, Ruijin Hospital Affiliated to Shanghai Jiaotong University, China (289). MAPT (rs17650901) tagging H1/H2 haplotype and SNCA (Rep1) were genotyped in the Australian cohort, and MAPT (rs242557, rs3744456) and SNCA (rs11931074, rs894278) were genotyped in the Chinese cohort. SPSS regression analysis was used to test genetic effects on age at onset of PD in each cohort. Results. SNCA polymorphisms associated with the onset age of PD in both populations. MAPT polymorphisms did not enhance such association in either entire cohort. Conclusion. This study suggests that, in both ethnic groups, SNCA gene variants influence the age at onset of PD and í µí»¼-synuclein plays a key role in the disease course of PD.BioMed Research International 08/2014; 2015. DOI:10.1155/2015/135674 · 2.71 Impact Factor
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- "These approaches have been attempted for motor, cognitive and psychopathological features of PD patients, while, they have not been attempted on findings of neuropathological and neuroimaging assessments. A recent comparison of the empirically assigned and data driven classification approaches (Marras and Lang, 2013) underlined how the former has the advantages of small number of subtypes, ease of implementation and assignment of patients to one or another subtype; on the contrary clusters derived "
ABSTRACT: Parkinson's disease (PD) is a neurological disorder, associated with rigidity, bradykinesia, and resting tremor, among other motor symptoms. In addition, patients with PD also show cognitive and psychiatric dysfunction, including dementia, mild cognitive impairment (MCI), depression, hallucinations, among others. Interestingly, the occurrence of these symptoms-motor, cognitive, and psychiatric-vary among individuals, such that a subgroup of PD patients might show some of the symptoms, but another subgroup does not. This has prompted neurologists and scientists to subtype PD patients depending on the severity of symptoms they show. Neural studies have also mapped different motor, cognitive, and psychiatric symptoms in PD to different brain networks. In this review, we discuss the neural and behavioral substrates of most common subtypes of PD patients, that are related to the occurrence of: (a) resting tremor (vs. nontremor-dominant); (b) MCI; (c) dementia; (d) impulse control disorders (ICD); (e) depression; and/or (f) hallucinations. We end by discussing the relationship among subtypes of PD subgroups, and the relationship among motor, cognitive, psychiatric factors in PD.Frontiers in Systems Neuroscience 12/2013; 7:117. DOI:10.3389/fnsys.2013.00117
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- "The easy method implemented in this study for characterizing motor subtypes may be a step forward to respond to the growing need and importance of classifying the PD subtypes in large clinical studies, due to the increasing evidence for biological and pathophysiological differences in the two subtypes , , . "
ABSTRACT: In this study, the use of an instrumented balance test based on inertial sensors was evaluated in patients with Parkinson's disease (PD). We aimed to objectively characterize motor subtypes of PD (tremor dominant, TD and postural instability gait difficulty, PIGD), to help to quantitatively classify the PD subjects into motor subtypes. Subjects were studied performing postural tests, while wearing a device including a tri-axial accelerometer on the lower back, in four different experimental conditions that depended on feet position (feet-together or semi-tandem) and vision (eyes open or closed). Postural measures, after a reliability check, were tested to identify their sensitivity to the disease, to the PD subtypes, and to the experimental conditions. The results highlight the possibility of distinguishing between the TD and PIGD subtypes by means of objective postural measures that are able to detect tremor and PIGD features and are able to classify a subject as TD or PIGD with good accuracy. Feet position influences frequency measures, whereas eyes closure influences the displacement measures and enhances differences between PD and control subjects, suggesting that postural displacement measures may be capable of detecting different adaptation processes to external sensory conditions between patients with PD and control subjects.IEEE transactions on neural systems and rehabilitation engineering: a publication of the IEEE Engineering in Medicine and Biology Society 12/2013; 22(5). DOI:10.1109/TNSRE.2013.2292496 · 2.82 Impact Factor