Risk factors for the development of freezing of gait in Parkinson’s disease patients

By Dr. Chinta SidharthanDec 6 2023Reviewed by Lily Ramsey, LLM

In a recent study published in the journal Npj Parkinson’s Disease, researchers meta-analyzed data obtained from a systematic review to understand the risk factors that influence the development of freezing of gait or FOG — a debilitating condition that occurs in some Parkinson’s disease patients.

Study: A meta-analysis identifies factors predicting the future development of freezing of gait in Parkinson’s disease. Image Credit: Chinnapong/Shutterstock.com

Background

One of the conditions that contributes to decreased mobility, increased risk of falls, and reduction in overall quality of life of individuals with Parkinson’s disease is FOG.

While numerous models and theories have been proposed to explain the development of FOG, the mechanistic triggers of FOG remain unclear.

Various therapies, such as medications for Parkinson’s disease, exercise, cueing, and non-invasive and invasive brain stimulation, have been applied to reduce the severity and frequency of FOG.

Studies have also investigated aspects related to depression, anxiety, executive function improvements, and various other domains of cognition to reduce the severity of FOG.

Although these therapies often lower the severity of FOG in the short term, the condition continues to worsen over time.

Given the numerous unsuccessful attempts to find effective therapies for FOG, a preventative approach by identifying potential risk factors that can be targeted and modified might prove to be effective. This requires a thorough understanding of the factors linked to the incidence of FOG.

About the study

In the present study, the researchers conducted a systematic review of studies reporting risk factors and early signs associated with FOG development among Parkinson’s disease patients.

Studies that had a prospective or retrospective cohort design involving adult Parkinson’s disease patients with a baseline diagnosis of no FOG were included in the review. The studies were also required to have baseline measurements of FOG predictors and follow-ups to assess incident FOG to be included in the review.

The general definition of FOG used in these studies was an episodic or brief absence or notable reduction in the forward progression of the feet, even with attempts to walk.

FOG was detected subjectively and objectively in the studies included in the review. Subjective detections were through self-reported responses to a question on whether the patient felt like their feet were glued to the floor and responses to various FOG questionnaires with and without showing the patients videos about freezing episodes. Objective assessments were conducted via neurological examinations or clinical observations.

The meta-analyses included assessment of baseline characteristics and calculations of standard mean difference for the continuous variables and risk ratio for categorical variables. Hazard ratios were calculated for characteristics without baseline data. The analyses were also stratified based on characteristics such as whether or not the patients were on medications at baseline.

A statistical homogeneity test was used to understand the included studies' variability and determine the heterogeneity's magnitude. Additionally, subgroup analyses were conducted for studies of high and low quality, retrospective or prospective design, short or long follow-ups, and short or long duration of Parkinson’s disease in the patient at baseline.

Results

The results indicated that factors such as increased age at the onset of Parkinson’s disease, anxiety, depression, low cognitive status, severe motor symptoms, and the use of catechol-O-methyltransferase (COMT) inhibitors or levodopa significantly increased the risk of FOG.

Furthermore, the subgroup analyses also reported robust results suggesting that in subsets of Parkinson’s disease patients, the changes linked to the incidence of FOG can be detected as early as 12 years before the manifestation of the condition.

Furthermore, many of the factors identified in the Parkinson’s disease patients who later developed FOG varied across individuals. A few of the risk factors were modifiable, highlighting potential avenues for preventing FOG.

While the mechanical relationships among the incidence, duration, and severity of FOG are complex, the results did find that the risk of developing FOG was higher when the duration of Parkinson’s disease was longer, and the severity was higher.

However, even in patients who had a shorter disease duration, a combination of other factors such as disease severity, balance impairment, depression, and anxiety could increase the risk of developing FOG in the future.

Conclusions

Overall, the findings suggested that the development of FOG in individuals with Parkinson’s disease could be predicted based on various risk factors, such as the duration and severity of the disease and the presence of anxiety, balance impairment, or depression.

Furthermore, these risk factors varied across individuals, but a few of them were modifiable, suggesting a potential for the prevention of FOG.