Longitudinal Prediction of Freezing of Gait in Parkinson's Disease: A Prospective Cohort Study

Abstract

Objective: Freezing of gait (FOG) is a disabling complication in Parkinson's disease (PD). Yet, studies on a validated model for the onset of FOG based on longitudinal observation are absent. This study aims to develop a risk prediction model to predict the probability of future onset of FOG from a multicenter cohort of Chinese patients with PD.Methods: A total of 350 patients with PD without FOG were prospectively monitored for ~2 years. Demographic and clinical data were investigated. The multivariable logistic regression analysis was conducted to develop a risk prediction model for FOG.Results: Overall, FOG was observed in 132 patients (37.70%) during the study period. At baseline, longer disease duration [odds ratio (OR) = 1.214, p = 0.008], higher total levodopa equivalent daily dose (LEDD) (OR = 1.440, p < 0.001), and higher severity of depressive symptoms (OR = 1.907, p = 0.028) were the strongest predictors of future onset of FOG in the final multivariable model. The model performed well in the development dataset (with a C-statistic = 0.820, 95% CI: 0.771–0.865), showed acceptable discrimination and calibration in internal validation, and remained stable in 5-fold cross-validation.Conclusion: A new prediction model that quantifies the risk of future onset of FOG has been developed. It is based on clinical variables that are readily available in clinical practice and could serve as a small tool for risk counseling.

Levodopa use in Australia: an analysis of Pharmaceutical Benefits Scheme 10% data

“…FOG is generally partially responsive to dopaminergic medication, and episodes are therefore more frequent and of longer duration when dopaminergic medication has worn off. Paradoxically, it has been found that higher daily doses of levodopa at baseline in a cohort study has been shown to predict worse FOG over time 26…”

Gait Declines Differentially in, and Improves Prediction of, People with Parkinson’s Disease Converting to a Freezing of Gait Phenotype

“…Prior reports of multivariable modeling also reflect a significantly diverse set of 40 features predicting FOGConv (Supplementary Table 3). Of these, 4 studies reported disease duration [49,51,57,62] and depression scores [48,49,52,62]; 3 datasets in 5 studies reported some variation of greater postural instability gait disorder (PIGD) scores [49,55,56,59,60]; and 2 studies reported age [49,60], LEDD [47,62] and gait speed [48,52] as predictors of FOG conversion. Two studies, both using the PPMI dataset, also reported lower CSF A␤ 42 levels [55,59] while one group reported decreased dopamine transporter tracer binding in two publications [55,56] as significant predictors of FOG conversion.…”

“…However, FOG has been reported in a percentage of patients even prior to initiation of levodopa therapy [56]. Phenotypic conversion to FOG has been associated with earlier levodopa use [61] and higher daily levodopa dose on univariate [49,50,57,61] and multivariable [47,62] analyses. In our study, duration of levodopa use and LEDD also both had AUC values of 0.775 and 0.815 respectively for classifying the noFOG and FOGConv groups (Supplementary Table 5), however these AUC values were lower than those for progression rates of gait parameters.…”

“…Several studies have now been published longitudinally monitoring conversion from a noFOG to a FOG phenotype [6,42,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] and are summarized in Supplementary Table 1. In the majority of these studies the focus was on motor and non-motor features at an initial enrollment visit that were not monitored longitudinally.…”

“…Univariate analysis from these studies identified 36 potential predictors (Supplementary Table 2), with greater age [59][60][61], higher levodopa equivalent dose [49,50,57,61], greater non-tremor dominant (TD) phenotype [49,55,59,60], higher non-motor scale or subscale scores [57,[59][60][61], higher depression rating scale scores [49,57,60,61], higher anxiety rating scale scores [49,57,61] and lower cognition scores [55,59,60] each noted as predictors in at least 3 studies. Multivariable analysis (Supplementary Table 3) similarly identified 40 different potential predictors, with disease duration [49,51,57,62] depression rating scale scores [48,49,52,62], greater postural instability gait disorder (PIGD) scores [49,55,56,59,60], age [49,60], levodopa equivalent daily dose (LEDD) [47,62], gait speed [48,…”