How Cognition and Motivation “Freeze” the Motor Behavior in Parkinson’s Disease

Abstract

ObjectiveFreezing of gait (FoG) is a debilitating problem in patients with PD. The multifactorial pathogenesis of FoG remains poorly understood. We aimed to find which factors are most strongly associated with the occurrence of FoG.MethodsThree hundred five PD patients were enrolled and subdivided according to the presence (FoG +, n = 128) or absence (FoG-, n = 177) of FoG. Several clinical, functional, and neuropsychological data were collected and compared between groups. The association between the probability of presence of FoG and possible explanatory variables was assessed by logistic regression analysis.ResultsFoG + patients were younger at the diagnosis (p = 0.04), and their mean daily dose of dopaminergic drugs (p < 0.0001) was higher in comparison with FoG- patients. FoG + patients get worse in Frontal Assessment Battery (p = 0.005), had higher scores in Apathy Evaluation Scale (p = 0.03), and were much more impaired on Wisconsin Card Sorting Test (WCST) (p = 0.018), Trail Making Test A (p = 0.0013), and Ray Auditory Verbal Learning Test (p = 0.012). Levodopa equivalent dose, age (direct), age at disease onset (inverse), and WCST were significant predictors of FoG (p = 0.01, p = 0.0025, p = 0.0016, and p = 0.029, respectively).ConclusionFoG + patients show more deficits in executive functions and in motivation. The main explanatory variables of FoG occurrence are levodopa equivalent dose, age, age at disease onset, and WCST. These data suggest that a specific involvement of frontal cortical circuits in PD is responsible for certain cognitive–behavioral alterations related to the occurrence of FoG.

Freezing of Gait in Parkinson’s Disease: Risk Factors, Their Interactions, and Associated Nonmotor Symptoms

“…We found FOG in PD to be unrelated to sex and only weakly associated with patient age, consistent with the majority of other prospective studies [ 4 , 8 , 10 – 12 , 30 ]. On the other hand, supporting extensive literature, we found disease duration to be strongly associated with FOG [ 4 – 7 , 9 , 12 , 13 , 31 ].…”

“…Levodopa equivalent dose was strongly correlated with motor complications ( p < 0.0001), supporting previous studies showing a strong relationship between levodopa dose and development of both wearing-off symptoms and dyskinesias [ 39 ], and was also confirmed as a significant independent risk factor for FOG in our logistic regression analysis. Levodopa dose has previously been linked to FOG in PD [ 7 , 8 , 10 ] and, in at least one study, was also shown to exert an effect on FOG independent from that of motor complications [ 8 ]. In our study, participants with motor complications who had a higher LED (≥750 mg) had more frequent freezing (67% versus 33%, p =0.009) but similar severity of freezing relative to those receiving a lower LED.…”

“…Although its pathophysiology remains incompletely understood, it is thought to reflect dysfunction in an integrated network of brain regions involved in locomotion [ 2 , 3 ]. Previously identified factors predisposing to FOG in PD include longer disease duration [ 4 – 7 ], more severe motor disability [ 6 – 8 ], higher nontremor score or PIGD phenotype [ 4 , 5 , 8 , 9 ], higher levodopa dose [ 7 , 8 , 10 ], motor fluctuations [ 6 – 8 ], hallucinations [ 8 , 11 , 12 ], and cognitive dysfunction, especially executive impairment [ 10 – 14 ]. The relative importance of these various factors in the genesis of FOG in PD and the ways in which such factors might interact has only recently started to receive attention [ 15 ].…”

Cross-sectional associations between cognition and mobility in Parkinson’s disease

“…Cognitive decline, especially in executive functions, has been associated with gait disorders and risk of falling. 16 , 20 The association between executive functions and bradykinesia has been reported in individuals with PD, 3 , 18 as well as the correlation between the ability to divide attention between two tasks and balance. 30 …”

“… 19 Executive function deficit, mainly inhibitory control and mental flexibility, has been associated with gait impairment and freezing of gait (FOG). 11 , 20 , 21 Another study revealed that gait and balance are related to specific cognitive skills, suggesting similar cerebral cortical circuitry for mobility and cognitive function. 13 …”