Association between Cognitive Impairment and Freezing of Gait in Patients with Parkinson’s Disease

Abstract

Background: Freezing of gait (FOG) is a common disabling symptom in Parkinson’s disease (PD). Cognitive impairment may contribute to FOG. Nevertheless, their correlations remain controversial. We aimed to investigate cognitive differences between PD patients with and without FOG (nFOG), explore correlations between FOG severity and cognitive performance and assess cognitive heterogeneity within the FOG patients. Methods: Seventy-four PD patients (41 FOG, 33 nFOG) and 32 healthy controls (HCs) were included. Comprehensive neuropsychological assessments testing cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function were performed. Cognitive performance was compared between groups using independent t-test and ANCOVA adjusting for age, sex, education, disease duration and motor symptoms. The k-means cluster analysis was used to explore cognitive heterogeneity within the FOG group. Correlation between FOG severity and cognition were analyzed using partial correlations. Results: FOG patients showed significantly poorer performance in global cognition (MoCA, p < 0.001), frontal lobe function (FAB, p = 0.015), attention and working memory (SDMT, p < 0.001) and executive function (SIE, p = 0.038) than nFOG patients. The FOG group was divided into two clusters using the cluster analysis, of which cluster 1 exhibited worse cognition, and with older age, lower improvement rate, higher FOGQ3 score, and higher proportion of levodopa-unresponsive FOG than cluster 2. Further, in the FOG group, cognition was significantly correlated with FOG severity in MoCA (r = −0.382, p = 0.021), Stroop-C (r = 0.362, p = 0.030) and SIE (r = 0.369, p = 0.027). Conclusions: This study demonstrated that the cognitive impairments of FOG were mainly reflected by global cognition, frontal lobe function, executive function, attention and working memory. There may be heterogeneity in the cognitive impairment of FOG patients. Additionally, executive function was significantly correlated with FOG severity.

Structural network topology correlates with cognitive impairment in Parkinson’s disease

“…In PD patients, blood perfusion was significantly decreased in right anterior cingulate cortex compared with the normal controls [49]. Furthermore, amplitude of low-frequency fluctuation in right anterior cingulate cortex was positively correlated with freezing of gait [50], which was causally associated with cognitive impairment in PD patients [4, 33]. Taken together, these findings suggested that right anterior cingulate cortex might play an essential role in the development of cognitive impairment in PD patients.…”

“…It can occur at any disease stage, even at the prodromal phase and early stage of the disease [2, 3]. It is associated with faster disease progression and worse prognosis [1, 4], which draws plenty of attention to promote the early diagnosis and treatment of cognitive impairment during PD management. According to previous literature, PD patients can display the impairments of multiple cognitive domains, spanning episodic memory [5], verbal memory [6], executive function [7], visuospatial ability [8], and processing speed [9].…”

Striatal dopamine depletion drives disease progression and network topology aberrations specifically by impairing left M1 network

“…[18][19][20][21] Cognitive impairment was also one of the most common non-motor features of PD patients 73 and associated with disease progression and outcome. [73][74][75] Cognitive impairment could occur at the early stage and even prodromal phase of PD. 73,[76][77][78] According to previous studies, PD patients could exhibit impairments of multiple cognitive domains, including verbal memory, [79][80][81] executive function, 82,83 visuospatial function, 84,85 episodic memory, [86][87][88] and processing speed.…”

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

“…Early hypotension, but not its symptom severity, increased dementia risk in PD patients by 14% while not being associated with other clinical or neuropathological variables [ 94 ]. PD patients with freezing of gait (FOG), an important risk factor for CI, exhibit worse global cognition, EF/attention, language memory and visuospatial functions [ 95 , 96 , 97 ]. Another risk factor for PDD is the overuse of anticholinergic drugs, especially in older PD patients with multimorbidities [ 98 ].…”