Motor, affective, cognitive, and perceptual symptom changes over time in individuals with Parkinson’s disease who develop freezing of gait

Freezing of gait (FOG) affects up to 80% of individuals living with advanced Parkinson’s disease and approximately 20% in early stages. Associated with motor, affective, cognitive, and sensory difficulties, FOG is challenging to treat due to its unknown etiology. Approaches and findings in research studies predicting FOG remain inconsistent. To help address discrepant methods and results, this prospective, longitudinal study evaluated motor, affective, cognitive, and perceptual predictors of FOG. Data from 120 individuals with idiopathic Parkinson’s disease from the Ontario Neurodegenerative Disease Research Initiative cohort were analyzed across two years to evaluate the strongest FOG predictors. Over this period, 25 individuals developed FOG (transitional freezers), 71 remained non-freezers, and the remaining 24 participants experienced freezing at baseline and follow-up (continuous freezers). Two-way Time*Group ANOVAs and non-parametric equivalents assessed data longitudinally. Separate logistic regression models evaluated FOG predictors one and two years prior to onset. Transitional freezers showed lower baseline immediate verbal recall z-scores than non-freezers. Transitional freezers’ dyskinesia severity, postural instability/gait difficulty, and depression increased, and attentional set-shifting and delayed visuospatial memory declined. Motor symptoms and longer disease duration predicted FOG two years prior, with affective and cognitive measures predictive one year prior. Models had high specificity (2 years: 97.0%, 1 year: 90.4%) but not sensitivity (2 years: 43.8%, 1 year: 52.9%), with accuracies of 86.7% and 81.2%, respectively. These findings highlight the change in FOG predictors relative to its onset time, which might explain conflicting findings to date. Future work should consider whether predictors vary by disease stage or FOG ‘subtype’.