Relationships between Freezing of Gait Severity and Cognitive Deficits in Parkinson’s Disease

Abstract

Freezing of gait (FOG) is one of the most debilitating motor symptoms experienced by patients with Parkinson’s disease (PD), as it can lead to falls and a reduced quality of life. Evidence supports an association between FOG severity and cognitive functioning; however, results remain debatable. PD patients with (PDFOG+, n = 41) and without FOG (PDFOG–, n = 39) and control healthy subjects (n = 41) participated in this study. The NIH toolbox cognition battery, the Montreal Cognitive Assessment (MoCA), and the interval timing task were used to test cognitive domains. Measurements were compared between groups using multivariable models and adjusting for covariates. Correlation analyses, linear regression, and mediation models were applied to examine relationships among disease duration and severity, FOG severity, and cognitive functioning. Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG– exhibited differences in Dimensional Change Card Sort (DCCS) test, interval timing task, and MoCA scores. After adjusting for covariates in two different models, PDFOG+ and PDFOG– differed in both MoCA and DCCS scores. In addition, significant relationships between FOG severity and cognitive function (MoCA, DCCS, and interval timing) were also found. Regression models suggest that FOG severity may be a predictor of cognitive impairment, and mediation models show the effects of cognitive impairment on the relationship between disease severity and FOG severity. Overall, this study provides insight into the relationship between cognitive and FOG severity in patients with PD, which could aid in the development of therapeutic interventions to manage both.

Functional Connectivity in Patients With Parkinson’s Disease and Freezing of Gait Using Resting-State EEG and Graph Theory

“…Interestingly, recent studies have shown a significant relationship between gait dysfunction/FOG and cognitive impairment in PD patients. 26,46 This relationship has been characterized by reduced midfrontal low-frequency oscillations in delta and theta frequency bands in PDFOG+ compared to PDFOG−. 6,7 Consistent with these reports, our PDFOG+ group showed lower MOCA scores compared to PDFOG−, suggesting higher cognitive deficits.…”

“…Similar to our previous studies, all participants with PD were tested while ON their usually prescribed dose of anti-parkinsonian medication, approximately 60 to 90 minutes from the last dose because fall risk is higher in unmedicated PDFOG+ patients and ON state is how people with PD are in daily life, so it is worth studying them in that state. 6,26 Disease and FOG severity in PD participants were assessed via the motor part of the Unified Parkinson’s Disease Rating Scale 27 and FOG questionnaire, respectively. 28 Similar to our previous studies, 6,7,26 PDFOG+ were grouped if they met both of the following criteria: (i) participants confirmed they had problems starting, stopping, and turning during walking; (ii) their FOGQ (number 3) score was >0, suggestive of at least 1 FOG episode in the past month.…”

“…6,26 Disease and FOG severity in PD participants were assessed via the motor part of the Unified Parkinson’s Disease Rating Scale 27 and FOG questionnaire, respectively. 28 Similar to our previous studies, 6,7,26 PDFOG+ were grouped if they met both of the following criteria: (i) participants confirmed they had problems starting, stopping, and turning during walking; (ii) their FOGQ (number 3) score was >0, suggestive of at least 1 FOG episode in the past month. Characteristics of all the participants have been described in Table 1.…”

Abnormal neural oscillations during gait and dual-task in Parkinson’s disease

“…Domellof and colleagues assessed gait stability, as quantitative gait assessment of UPDRS subitems, and observed a consistent association with visuospatial abilities ( Domellof et al, 2011 ). Our recent study using regression models suggests that FOG severity may be an indicator of a more global cognitive impairment, and that disease severity is correlated with both FOG and abnormal cognitive functioning scores ( Scholl et al, 2021 ). Consequently, cognitive training has been shown to improve gait functions in PD patients with FOG (PDFOG+), compared to PD patients without FOG (PDFOG–) ( Walton et al, 2018 ).…”

“…As the disease progresses, PD patients also exhibit more expressed deficits during dual-task activities compared to single-task testing, since a more pronounced cognitive impairment can be seen in the advanced stages of the disease ( Kelly et al, 2012a , b ; Stegemoller et al, 2014 ; Scholl et al, 2021 ). Recent studies have demonstrated the contribution of cortical and subcortical neural activity to single- and dual-task lower-extremity motor and gait performances ( Singh et al, 2013 , 2020 ; Pizzamiglio et al, 2017 ; Singh, 2018 ).…”