Neurology. 2025 Sep 23;105(6):e214033. doi: 10.1212/WNL.0000000000214033. Epub 2025 Aug 20.
ABSTRACT
BACKGROUND AND OBJECTIVES: The association between metabolic syndrome (MetS) and incident Parkinson disease (PD) remains equivocal. We aimed to investigate the association of MetS and its components with the risk of PD and to explore the role of genetic background in the MetS-PD association.
METHODS: This prospective cohort study included PD-free adults aged 37-73 years from the UK Biobank. MetS was defined as presence of 3 or more of the following: elevated waist circumference (≥102 cm for men; ≥88 cm for women), hypertension (systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥85 mm Hg, or use of antihypertensive medication), dyslipidemia (high-density lipoprotein cholesterol <1.04 mmol/L for men or <1.30 mmol/L for women or use of lipid-lowering medication), hypertriglyceridemia (triglycerides ≥1.70 mmol/L or use of lipid-lowering medication), and hyperglycemia (HbA1c ≥ 5.7%). PD was diagnosed based on information from medical records. PD-related polygenic risk score (PRSPD) was calculated based on the presence of 26 PD-related alleles and categorized as low, moderate, or high. Data were analyzed using Cox regression. In addition, a meta-analysis was conducted by integrating the present UK Biobank data with findings from 8 other observational studies.
RESULTS: The study included 467,200 participants (mean age 56.53 ± 8.09 years; 54.26% female), 177,407 (37.97%) of whom had MetS. Over the follow-up (6,605.9 × 1,000 person-years), 3,222 participants developed PD (5.01 [95% CI 4.84-5.18] per 10,000 person-years, age-specified and sex-specified). The hazard ratio of PD was 1.39 (1.11-1.74) for participants with MetS compared with those who were MetS-free. Furthermore, having a higher number of MetS components was dose-dependently associated with higher PD risk (HR: 1.14 [1.05-1.24]; p for trend = 0.001). In addition, PD risk was highest among participants with MetS and high PRSPD (HR: 2.58 [2.12-3.14]; p for interaction = 0.002). In a meta-analysis of 24,789,538 participants with 98,582 incident cases of PD, the pooled relative risk of PD was 1.29 (1.15-1.44) for participants with MetS.
DISCUSSION: Supported by evidence from meta-analysis, MetS was associated with higher risk of incident PD, especially in people with a high genetic predisposition for PD.
PMID:40834329 | DOI:10.1212/WNL.0000000000214033
