Parkinson's disease subtypes: Lost in translation?

Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Ontario, Canada.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 09/2012; 84(4). DOI: 10.1136/jnnp-2012-303455
Source: PubMed


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.

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    • "One study found that non-tremor dominant cases were more likely to have neocortical Lewy body disease, whereas tremor dominant cases were more likely to have brainstem/limbic pathology (Marras and Lang 2013; Selikhova et al. 2009). Insecticides and fungicides may be more particularly associated with tremor-dominant PD because of the vulnerability of dopaminergic neurons in the substantia nigra to mitonchondrial inhibitors and oxidative stressors; further work is needed to better understand the etiology of PD subtypes. "
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    ABSTRACT: Pesticides have been associated with Parkinson's disease (PD), but there are few data on important exposure characteristics such as dose-effect relations. It is unknown whether associations depend on clinical PD subtypes. We examined quantitative aspects of occupational pesticide exposure associated with PD and investigated whether associations were similar across PD subtypes. As part of a French population-based case-control study including men enrolled in the health insurance plan for farmers and agricultural workers, cases with clinically confirmed PD were identified through antiparkinsonian drug claims. Two controls were matched to each case. Using a comprehensive occupational questionnaire, we computed indicators for different dimensions of exposure (duration, cumulative exposure, intensity). We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CI) among exposed male farmers (133 cases, 298 controls). We examined the relation between pesticides and PD subtypes (tremor dominant/non-tremor dominant) using polytomous logistic regression. There appeared to be a stronger association with intensity than duration of pesticide exposure based on separate models and a synergistic interaction between duration and intensity (p-interaction = 0.04). High intensity exposure to insecticides was positively associated with PD among those with low intensity exposure to fungicides and vice versa, suggesting independent effects. Pesticide exposure in farms specialized in vineyards was associated with PD (OR = 2.56; 95% CI: 1.31, 4.98). The association with intensity of pesticide use was stronger, although not significantly (p-heterogeneity = 0.60), for tremor dominant (p--trend < 0.01) than for non-tremor dominant PD (p--trend = 0.24). This study helps to better characterize different aspects of pesticide exposure associated with PD, and shows a significant association of pesticides with tremor dominant PD in men, the most typical PD presentation.
    Environmental Health Perspectives 03/2015; DOI:10.1289/ehp.1307970 · 7.98 Impact Factor
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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 [1] [2]. Patients with young disease onset often have a benign disease course and a lower rate of dementia compared to those with later disease onset [3], and previous studies show that genetic factors influence both the age of onset [4] [5] and clinical subtypes of PD [6] [7] [8]. "
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    ABSTRACT: Background: α-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 α-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 "
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    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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