Objective: To explore which symptoms contribute to the future development of freezing of gait (FOG) in Parkinson’s disease (PD) patients without FOG.

Background: Prospective studies describing the natural history of FOG in PD are limited and it is not yet clear who are the subjects that will develop FOG as the disease progresses.

Methods: Fifty seven PD patients without FOG (age 65.2±9.5 yrs; 32% female; disease duration: 4.4±2.6 yrs) at baseline were re-evaluated five years later. At baseline, disease severity (UPDRS on and off medication), gait under single and dual task, balance, cognitive function and non-motor symptoms were assessed. The new-FOG-questionnaire (NFOG-Q) was used to distinguish people who developed freezing 5 years later (FOG+) from those who did not, i.e., non-freezers (FOG-). Multivariate binary logistic regression determined independent predictors of FOG.

Results: At follow-up, 26 subjects (46%) had FOG (NFOG-Q>0) while 31 participants remained non-freezers (NFOG-Q=0). At baseline, FOG+ and FOG- were similar (p>0.10) with respect to age, gender, disease duration, levodopa equivalent daily dose, and the Montreal cognitive assessment scores. However, FOG+ had worse scores (p<0.05) on the Geriatric Depression Scale (GDS) (FOG+:5.2±3.7; FOG-:2.4±2.0), PDQ-39, the NMS-questionnaire, UPDRS-I, UPDRS-III (off), and the Berg Balance Scale. In binary logistic regression, GDS scores and UPDRS-III at off were the only significant independent predictors of future FOG (GDS: OR=1.42, 95% CI:1.12-1.81; p=0.004, UPDRS-III: OR=1.07, 95% CI:1.01-1.13; p=0.02). Moreover, 80% of the subjects who had marked depressive symptoms at baseline (GDS≥5) developed FOG within the 5 years follow-up. In contrast, among those with few depressive symptoms at baseline (GDS<5), only 27% developed FOG (p<0.001).

Conclusions: Although FOG is typically considered a motor disturbance, non-motor features, especially depressive symptoms, apparently precede the development of FOG. This early marker may promote the elucidation of the mechanisms that lead to FOG and help clinicians to estimate a patient’s risk of developing freezing of gait in the future.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/depressive-symptoms-may-predict-the-future-development-of-freezing-of-gait-in-patients-with-parkinsons-disease-findings-from-a-5-year-prospective-study/