Depressive Symptoms May Increase the Risk of the Future Development of Freezing of Gait in Patients with Parkinson's Disease: Findings from a 5-year Prospective Study

Introduction: Prospective studies identifying predictors of freezing of gait (FOG) in Parkinson's disease (PD) are limited. We aim to explore which symptoms are associated with future development of FOG in non-freezers.

Methods: Fifty-seven PD patients without FOG at baseline were re-evaluated after a mean of five years. At baseline, disease severity [Unified Parkinson's Disease Rating Scale (MDS-UPDRS)], gait under single and dual-tasking, balance, cognition and other non-motor symptoms were assessed. The new-FOG-questionnaire (NFOG-Q) determined FOG. Multivariate binary logistic regression determined independent predictors of FOG.

Results: At follow-up, 26 subjects (46%) had FOG while 31 remained non-freezers. At baseline, non-freezers (FOG-) and future freezers (FOG+) were similar (p > 0.10) with respect to age, gender, disease duration, dopaminergic medications, and cognitive function. However, FOG + had significantly worse scores on the Geriatric Depression Scale (GDS) (FOG+:5.2 ± 3.7; FOG-:2.4 ± 2.0, p = 0.005), PDQ-39, the NMS-questionnaire, UPDRS-part I, UPDRS-part III (off), and the Berg Balance Scale. In binary logistic regression, GDS, gait speed and UPDRS-III (on vs. off) were the only significant independent predictors of future FOG (GDS: OR = 10.93, p = 0.003, ΔUPDRS-III: OR = 1.34, p = 0.006). Moreover, 80% of the subjects who had marked depressive symptoms at baseline (GDS≥5) developed FOG at follow-up. In contrast, only 27% of those with few depressive symptoms at baseline became freezers (p < 0.001).

Conclusions: Depressive symptoms apparently precede the development of FOG. While elucidation of the relationship between depression and FOG needs further study, our findings offer another perspective regarding the pathophysiology of FOG and may help clinicians to estimate the risk of developing this debilitating phenomenon.