Freezing of gait is a risk factor for cognitive decline in Parkinson's disease

Backgrounds Freezing of gait (FOG) and cognitive impairment are serious symptoms of Parkinson's disease (PD). Understanding the association between FOG and cognition may help formulate specific interventions for PD individuals. Objectives We aimed to investigate the associations of cognitive impairment in different domains with FOG status using multiple neuropsychological tests. Methods Two cohorts including 691 and 104 participants were recruited from Parkinson's progression markers initiative (PPMI) and central China, respectively. All participants underwent FOG assessment and neuropsychological tests, and 595 individuals from PPMI and 51 from central China were enrolled for longitudinal observation. Cross-sectional and longitudinal associations between cognition and FOG status were evaluated using multivariable-adjusted models. Results Worse cognitive performances were observed in patients with FOG compared to those without FOG in both cohorts (beta = - 0.020, p < 0.001) using multivariate-adjusted models. Moreover, patients with progressive FOG during follow-up manifested more serious cognitive declines (HR = 1.40, 95% CI = 1.07-1.80). The FOG was mainly associated with the decline of executive, attention, and orientation. Furthermore, FOG was associated with higher levels of cognition-related biomarkers including T-tau, P-tau, and NfL in cerebrospinal fluid (p < 0.050). Conclusions FOG is a risk factor for cognitive decline in PD, which emphasizes the need for early detection and monitoring of cognitive changes and interventions on cognitive impairments in PD patients with FOG.