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.
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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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ABSTRACT: Parkinson's disease (PD) is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) subtypes. However, objective measures of gait (e.g., stride length, variability) and balance have not been well studied in these subtypes. To better understand these motor subtypes, we objectively quantified gait and balance and their behavioral correlates. 110 patients with PD underwent a clinical evaluation and were stratified into PIGD and TD subtypes. Participants walked under single and dual task conditions while wearing a single body-fixed sensor, both "OFF" and "ON" medications and at home for 3 days. We also examined performance-based tests of mobility, balance, and fall risk. Stricter criteria were also applied, dividing the subjects into predominant representative subgroups: p-PIGD and p-TD. Both the PIGD (n = 62) and TD (n = 42) groups and the p-PIGD (n = 31) and p-TD (n = 32) subgroups were similar with respect to basic disease characteristics (e.g., disease duration, p > 0.69). Surprisingly gait speed, stride length, and variability did not differ between the PIGD and TD groups (p > 0.05). In contrast, the p-PIGD group had reduced gait speed (under single and dual task conditions), shorter strides, increased stride variability, and decreased stride regularity (regularity: p-PIGD 0.66 ± 0.10; p-TD 0.74 ± 0.08; p = 0.003). The p-PIGD group also scored worse on performance-based tests, compared to the p-TD. Clinical assessments of the disturbances seen in patients with the PIGD subtype are not consistent with objective measures; overlapping between the groups is seen in many objective features of gait and balance. These findings suggest that the proposed alternate classification scheme may be useful.Journal of Neurology 09/2014; DOI:10.1007/s00415-014-7513-6 · 3.84 Impact Factor
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ABSTRACT: Purpose Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. Methods [I-123]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Results Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p<0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p<0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. Conclusion The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor.European journal of nuclear medicine and molecular imaging 05/2014; 41(10). DOI:10.1007/s00259-014-2796-5 · 5.22 Impact Factor