Disease progression in Parkinson subtypes: the PPMI dataset

Area of Science:

• Neurology
• Neuroscience
• Movement Disorders

Background:

• Parkinson disease (PD) progression patterns vary, with suggested subtypes like tremor-dominant (TD) and postural instability gait disorder (PIGD).
• Clinical classification of PIGD is unstable, with only 40% retaining the subtype over time.
• Longitudinal studies require consideration of this clinical variability.

Purpose of the Study:

• To compare the longitudinal clinical progression of PIGD versus TD subtypes in Parkinson disease.
• To analyze progression using a stricter definition of PIGD/TD subtypes to account for classification instability.

Main Methods:

• Analysis of longitudinal clinical data from the Parkinson Progression Markers Initiative (PPMI) cohort.
• Inclusion of patients consistently classified as PIGD or TD across all 4-year visits.
• Application of linear mixed-effects models to assess progression in 51 dependent variables.

Main Results:

• PIGD patients (36/254) exhibited more severe motor disease at baseline compared to TD patients (144/254).
• PIGD showed faster progression in non-motor symptoms: cognitive impairment, hallucinations, and psychosis with Drug-Induced Sleep (DDS) features.
• PIGD also demonstrated a faster increase in average time with dyskinesia.

Conclusions:

• PIGD subtype in Parkinson disease is associated with greater baseline severity and accelerated cognitive progression.
• PIGD patients experience more frequent hallucinations, psychosis, and DDS features, indicating broader cortical and subcortical involvement.
• Stricter PIGD/TD classification criteria offer valuable insights for clinical trial design and outcome measure development in Parkinson disease research.