Objective: Freezing of gait (FOG) is one of common and disabling gait impairments of Parkinson's disease (PD). White matter hyperintensity (WMH) and lacunes, as common manifestations of cerebral small vessel diseases (CSVD), have been reported to be associated with gait function in PD patients. However, in the cases with FOG which present with extensive WMH or lacunes, it actually is difficult to distinguish pure PD pathology from vascular origin or combined effects. So far little is known about the correlation between enlarged perivascular space (PVS) and FOG in PD patients. This study aims to explore the role of enlarged PVS in FOG in PD patients.Methods: A total of 95 patients with PD in the absence of obvious WMH and lacunes were included in our study, which were divided into PD-FOG (+) group and PD-FOG (-) group. Demographic and clinical data were investigated. Enlarged PVS in the centrum semiovale (CSO) and basal ganglia (BG) were assessed. The association between enlarged PVS and FOG in patients with PD was analyzed using the multivariate models and the Spearman's correlation.Results: There were 36 PD patients grouped into PD-FOG (+) (37.9%), with an older age, a longer PD disease duration, and larger numbers of enlarged PVS in CSO and BG compared with PD-FOG (-) group. The highest-severity degree of enlarged PVS burden in CSO was independently associated with FOG in patients with PD [adjusted odds ratio (OR), 3.869; p = 0.022 in multivariable model]. The percentages of FOG case increased accompanied by the aggravation of enlarged PVS located in CSO. The grade and count of enlarged PVS in CSO and BG both correlated with FOGQ score in PD patients.Conclusion: Enlarged PVS, particularly in CSO, are associated with FOG in patients with PD, which provides a novel perspective for the mechanisms of FOG in PD.

Purpose: Parkinson’s disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. This study aims to explore the cognitive profiles stratified by education using MoCA in PD patients with FOG. Patients and Methods: PD patients with FOG (FOG+, n = 52) and without FOG (FOG-, n = 71) were included in our study. MoCA items were categorized into five subsections (attention/working memory, executive function, episodic memory, language, and visuospatial function) referring to previously published criteria. Cognitive assessments were compared based on five subsections between groups stratified by three education levels (0– 6 years, 7– 12 years, and > 12 years). The association of cognitive measurements with FOG were analyzed using binary logistic regression models with adjustment for variables. Results: The total scores and subscores of each subsection of MoCA were similar between two groups of each education level. Further detailed analysis showed that a composite measure labeled “Attention/working memory-Composite” (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition), were lower significantly in FOG+ group compared with FOG- group in patients with education year ≤ 6 years. The significant association of Attention-C with FOG held true when controlling for disease duration, but not for H-Y stage, MDS-UPDRS III, HAMA, and HAMD. Conclusion: Overall, our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which will need to be validated in future studies. Plain Language Summary: Parkinson’s disease (PD) patients with freezing of gait (FOG) may present with complex and heterogeneous cognitive profiles. Owing to limited access to comprehensive neuropsychological battery in ordinary clinical practice, the Montreal Cognitive Assessment (MoCA) is likely to be easily available cognitive data for comparisons among studies. To the best of our knowledge, our study is the first to investigate the cognitive profiles using MoCA stratified by education in Chinese PD patients with FOG. We proposed a novel composite measure derived from MoCA labeled “Attention/working memory-Composite” (abbreviated to Attention-C), consisting of the scores of four items (target detection task, serial sevens, digit forward and backward, and sentence repetition). We found a significant association of Attention-C with FOG existed in PD patients with education year ≤ 6 years when controlling for disease duration, but disappeared for H-Y stage, MDS-UPDRS III, HAMA, and HAMD. It may be attributed to a large extent to the relatively small size of our study population. Our findings gave a hint that Attention-C derived from MoCA might be a potential factor associated with FOG in PD patients with lower education level (education year ≤ 6 years), which need to be further explored and validated in expanded studies with different international populations. Thus, the present study could provide critical implications for ordinary clinical practice where comprehensive neuropsychological batteries are not easily accessible to clinicians.