Executive functioning and serum lipid fractions in Parkinson’s disease—a possible sex-effect: the PACOS study

Abstract

The association between dyslipidemia and cognitive performance in Parkinson’s disease (PD) patients still needs to be clarified. Aim of the study was to evaluate the presence of possible associations between serum lipids fractions and executive dysfunction also exploring the sex-specific contribute of lipids level on cognition. Patients from the PACOS cohort, who underwent a complete serum lipid profile measures (total cholesterol-TC, low-density lipoprotein cholesterol-LDL, high-density lipoprotein cholesterol-HDL and triglycerides-TG) were selected. Adult Treatment Panel III guidelines of the National Cholesterol Education Program were used to classify normal/abnormal lipid fractions. Executive functioning was assessed with the Frontal Assessment Battery (FAB). Logistic regression was performed to assess associations between lipids fractions and FAB score. Correlations between lipids fractions and FAB score were explored. Sex-stratified analysis was performed. Three hundred and forty-eight PD patients (148 women; age 66.5 ± 9.5 years; disease duration 3.9 ± 4.9 years) were enrolled. Women presented significantly higher TC, LDL and HDL than men. In the whole sample, any association between lipid profile measures and FAB score was found. Among women, a positive association between hypertriglyceridemia and FAB score under cutoff was found (OR 3.4; 95%CI 1.29–9.03; p value 0.013). A statistically significant negative correlation was found between the FAB score and triglyceride serum levels (r = − 0.226; p value 0.005). Differently, among men, a statistically significant negative association between hypercholesterolemia and FAB score under cutoff (OR 0.4; 95%CI 0.17–0.84; p value 0.018) and between high LDL levels and FAB score under cutoff (OR 0.4; 95%CI 0.18–0.90; p value 0.027) were found. Our data suggest a sex-specific different role of lipids in executive functioning.

Sex Differences in Parkinson’s Disease: From Bench to Bedside

“…Particular circulating NAPE species serum levels are significantly lower in PD patients compared to healthy controls, with a stronger decrement in female PD patients [ 6 ]. Luca et al evaluated the role of serum lipid fractions as potential biomarkers for cognitive decline in a large cohort of PD patients, finding a sex-specific different contribute of lipids fractions on cognitive performance in PD, i.e., the association between hypertriglyceridemia and executive dysfunction only in women [ 7 ].…”

“…(3) Fear recognition was positively related with estrogen levels in female patients Luca [7] Cross (2) Among men, an inverse association was found between hypercholesterolemia and normal FAB performance. The main effect of APOE4 on the change in the MoCA score was not significant for either men or women.…”

Sex differences in alpha-synucleinopathies: a systematic review

“…In lipid profiling studies, there is a mutual agreement on sex-specific lipid profiling and functioning in cognitive manifestations of PD ( 96 , 97 ). For example, in female PwP, a positive association between hypertriglyceridemia and cognitive performance on the Frontal Assessment Battery (FAB) task was found ( p = 0.013) and a negative correlation between triglyceride serum levels and cognitive performance on FAB task ( p = 0.005) ( 96 ). However, in male PwP, a negative association was found between hypercholesterolemia and normal FAB performance and between high low-density lipoprotein cholesterol levels and FAB score ( p = 0.027) ( 96 ), suggesting a differential functional role of lipids in sex-specific phenotype presentation of symptoms.…”

“…Metabolites and lipoproteins could also serve as sensitive biomarkers in identifying sex-specific profiles of PD (95)(96)(97)(98)(99). In lipid profiling studies, there is a mutual agreement on sex-specific lipid profiling and functioning in cognitive manifestations of PD (96,97).…”

“…Metabolites and lipoproteins could also serve as sensitive biomarkers in identifying sex-specific profiles of PD (95)(96)(97)(98)(99). In lipid profiling studies, there is a mutual agreement on sex-specific lipid profiling and functioning in cognitive manifestations of PD (96,97). For example, in female PwP, a positive association between hypertriglyceridemia and cognitive performance on the Frontal Assessment Battery (FAB) task was found (p = 0.013) and a negative correlation between triglyceride serum levels and cognitive performance on FAB task (p = 0.005) (96).…”