Clinical subtypes of Parkinson's disease

Abstract

The clinical heterogeneity of Parkinson's disease (PD) may point at the existence of subtypes. Because subtypes likely reflect distinct underlying etiologies, their identification may facilitate future genetic and pharmacotherapeutic studies. Aim of this study was to identify subtypes by a data-driven approach applied to a broad spectrum of motor and nonmotor features of PD. Data of motor and nonmotor PD symptoms were collected in 802 patients in two different European prevalent cohorts. A model-based cluster analysis was conducted on baseline data of 344 patients of a Dutch cohort (PROPARK). Reproducibility of these results was tested in data of the second annual assessment of the same cohort and validated in an independent Spanish cohort (ELEP) of 357 patients. The subtypes were subsequently characterized on clinical and demographic variables. Four similar PD subtypes were identified in two different populations and are largely characterized by differences in the severity of nondopaminergic features and motor complications: Subtype 1 was mildly affected in all domains, Subtype 2 was predominantly characterized by severe motor complications, Subtype 3 was affected mainly on nondopaminergic domains without prominent motor complications, while Subtype 4 was severely affected on all domains. The subtypes had largely similar mean disease durations (nonsignificant differences between three clusters) but showed considerable differences with respect to their association with demographic and clinical variables. In prevalent disease, PD subtypes are largely characterized by the severity of nondopaminergic features and motor complications and likely reflect complex interactions between disease mechanisms, treatment, aging, and gender.

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

“…Several studies indicated that the clinical course and progression of PD are very variable, suggesting the presence of different PD subtypes with a different evolution [26] and [27]. Young age at PD onset has been associated with a slow-progressive disease, with few non-levodopa-responsive symptoms but a higher incidence of motor fluctuations and dyskinesias [28], while a clinical phenotype characterized by the presence of postural instability and gait difficulty (PIGD) seems to be linked to a rapidly-progressive PD course [29].…”

Urinary dysfunction with detrusor hyperactivity in women with Parkinson's disease cannot be blamed as a factor of worsening motor performance

“…The issue of clinical heterogeneity has been studied by analyzing subgroups distinguished by age, progression, and clinical symptoms associated with motor patterns, such as dementia, depression, and autonomic symptoms. In a recent European systematic review conducted by van Rooden et al 23 , clinical forms have been grouped into four subtypes categorized by differences in severity of nondopaminergic aspects and motor complications 23 . Characterization of subtypes and the evolution of the disease can define the prognosis and determine therapeutic strategies, creating a growing demand to identify nonmotor clinical aspects of PD such as urinary dysfunction and determine its role as a prognosis factor.…”

Parkinson's disease – pathology, aetiology and diagnosis

“…130 A further analysis has suggested that PD sub-types can be largely characterized by the severity of non-dopaminergic features and motor complications and are likely explained by interactions between disease mechanisms, treatment, ageing and gender. 131 Another recent study (PD PROMS group) has looked at the association between motor subtypes and mood. Regression models suggested an increased risk of anxiety in patients with younger age-of-onset and motor fluctuations.…”