Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach

Abstract

Objective: To investigate the heterogeneity of idiopathic Parkinson's disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established diagnostic criteria. Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I-III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored. Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment. Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson's disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment.

Parkinson's disease motor subtypes and mood

“…Motor subtype was identified as PIGD or tremor dominant/indeterminate [40] and as tremor dominant or non-tremor dominant (akineticrigid). [10] Patients were also classified according to whether they reported postural instability and falls (PIF) (UPDRS Part II item 13>1) and freezing of gait (FOG) (UPDRS Part II item 14>1). [16] Rate of disease progression was estimated from cross-sectional data by dividing the UPDRS-III total by duration of disease since diagnosis in years [10] and dichotomized on the sample median.…”

“…[10] Patients were also classified according to whether they reported postural instability and falls (PIF) (UPDRS Part II item 13>1) and freezing of gait (FOG) (UPDRS Part II item 14>1). [16] Rate of disease progression was estimated from cross-sectional data by dividing the UPDRS-III total by duration of disease since diagnosis in years [10] and dichotomized on the sample median. Motor complications of treatment (present or absent) were defined as motor fluctuations and/or sudden onset fluctuations (UPDRS Part IV).…”

“…[9] Depression has been linked to the akinetic-rigid form of PD compared to patients with a tremor dominant profile [10][11][12][13], and in patients with postural instability and gait disturbance (PIGD) particularly falls, versus those with a non-PIGD profile [13][14][15][16]. Depression has also been associated with more rapid progression [10;17;18], and with motor complications of therapy [15;19] although not in all studies.…”

Parkinson's disease severity and motor subtype influence physical capacity components

“…Lewis et al, 2005): akinetic-rigidity (AR) and tremor-dominant (TD) subtypes. AR is mainly characterized by a reduction in the movement velocity (bradykinesia), difficulties in the initiation of movements (akinesia) and an increase in muscle tone (rigidity).…”

Different patterns of cardiac sympathetic denervation in tremor-type compared to akinetic-rigid-type Parkinson’s disease: Molecular imaging with 123I-MIBG

“…The motor part of the UKPDSBB criteria was used to assess the severity of disease (10). On the basis of the predominant motor features in UPDRS III motor examination section score, patients were subtyped into one of two clinical groups, ART and TDT, following the methods described in previous studies (11)(12)(13)(14). The Mini Mental State Examination (MMSE) did not reveal any cognitive deficit.…”