Differential effects of cholesterol levels on cognition according to body mass index in Parkinson’s disease

Background: Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson’s disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD. Methods: This study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion. Results: TC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (β = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (β = − 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014). Conclusions: This study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD.