Metabolic Syndrome and Parkinson’s Disease: Two Villains Join Forces

Background. Metabolic syndrome and Parkinson’s disease share common pathophysiological mechanisms. This study aimed to investigate the metabolic syndrome’s contribution to Parkinson’s disease progression and the genetic traits associated with PD and MetS. Methods. Four hundred and twenty-three newly diagnosed drug-naïve PD patients were analyzed from the Parkinson’s Progression Markers Initiative (PPMI) database. We compared changes in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score and subscores in Parkinson’s patients with or without metabolic syndrome during the first 5 follow-up years. Then, we compared the frequency of PD-related variants in patients with or without MetS. Results. At baseline, Parkinson’s patients with MetS were typically men (p<0.01), and older (p=0.04), with a higher Hoehn and Yahr score (p=0.01) compared with their counterparts without MetS. They showed higher Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total scores at baseline and in follow-up years 2, 3, 4, and 5 (all p-values <0.05) as analyzed by the Generalized Estimating Equation model. This was due to an increased motor — MDS-UPDRS Part III — score (p<0.01). MetS was associated with a higher frequency of the ZNF646.KAT8.BCKDK_rs14235 variant and a lower frequency of the variants NUCKS1_rs823118 and CTSB_rs1293298. Conclusions. PD patients with MetS had worse motor symptomatology. Both diseases shared genetic background, including mutations in genes participating in lipids metabolism (BCKDK), autophagy and inflammatory responses (CTSB), and chromatin regulation (NUCKS1).