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Remor, bradykinesia and axial scores) Intermediate Progression rate Intermediate depression, anxiousness and frontal cognitive impairment High NMS score (Urinary domain selectively impacted)Group 4 - MD (n = 20) 62 years at onset Higher UPDRS III score (with high bradykinesia and axial scores) Higher Progression rate High depression, anxiety and frontal cognitive impairment Intermediate NMS scoreIntermediate UPDRS III score (with mild Low UPDRS III score (with low tremor tremor and bradykinesia scores) and bradykinesia scores) Intermediate Progression rate Low Progression rate Absent depression, anxiousness and frontal cognitive impairment Extremely low NMS score (Memory, Sleep and Psychiatric domains selectively spared) doi:10.1371/journal.pone.0070244.t004 Mild depression, anxiousness and frontal cognitive impairment Intermediate NMS score (Sex domain selectively impacted)The Heterogeneity of Early Parkinson's DiseaseFigure 1. Summary of key features in the clusters in accordance with clinical involvement, severity and age at onset. doi:ten.1371/journal.pone.0070244.gscores measuring total NMS and NMS-D reflect additional the involvement of various non-motor domains, rather than an index of their severity. It implies that the NMD cluster would have widespread involvement of NMS-D, but milder non-motor severity (at the least concerning depression, anxiety and frontal impairment) when compared with MD group, possibly suggesting a mild to moderate dopaminergic degeneration (as also confirmed by the intermediate motor scores) plus the involvement of extra-dopaminergic systems, which as an alternative could be fairly spared in the MD group. The latter would consequently show an attitude for the involvement of such non-motor functions (i.e. frontal-type cognitive deficits and neuropsychiatric issues), which have been consistently linked towards the striatal dopaminergic denervation [12,40?4], whereas the NMD cluster would have a widespread involvement of several NMS-D, with possibly further underpinning mechanisms. 1 would suspect some NMS-D like urinary, gastrointestinal and cardiovascular (i.e. all domains which have been to supposed to become part of the autonomic technique) to travel collectively. We failed to determine clear patterns of non-motor grouping in such sense. A limitation which might accounts for this can be that the NMSQuest merely detects the involvement of various domains, such as for instance the gastrointestinal, which could be not particular for PD. Moreover, by considering disaggregated products in line with their own relevance (i.e., not the raw quantity of gastrointestinal symptoms but a measure of your intensity of each and every one particular of them), it may be attainable to disclose a lot more delineated non-motor grouping. The relative low frequency of some NMS (because of the nature of our cohort of de-novo patients) may possibly have further accounted for such lack of non-motor grouping. Nonetheless, we identified clear nonmotor variations involving groups. As an illustration, NMD is characterized by urinary issues although MD is characterized by cognitive/neuropsychiatric symptoms, suggesting that these twoNMS-D travel separately, in line with other reports [45]. It may additional indicate that such two groups (i.e., the ``advanced clusters, which to some extent share a popular pattern of motor disability) may be prone to develop either autonomic or neuropsychiatric issues, respectively, but this desires to become EMD 121974 site clarified in additional longitudinal research. Finally, the logistic regression showed that total UPDRS III, Sexual disturbances and Acting out d.