Large 15-year study links metabolic syndrome to increased risk of Parkinson's disease

A population-based study of 467,200 participants (mean age 57 years) published in the journal Neurology showed that the presence of metabolic syndrome (MetS) is associated with an approximately 40% higher risk of subsequently developing Parkinson's disease compared with people without MetS. Over a median follow-up of 15 years, 3,222 people were diagnosed with Parkinson's. The baseline incidence rates were 4.87 cases per 10,000 person-years in people without MetS versus 5.21 per 10,000 person-years in people with MetS. The association remained after adjusting for age, smoking, physical activity, and genetic predisposition to Parkinson's. The authors additionally collected a meta-analysis of previous studies: when taken together with eight earlier studies, people with MetS had a 29% higher risk of Parkinson's.

Background of the study

Parkinson's disease (PD) is increasingly being considered not only as a "local" neurodegeneration, but as a systemic disorder with metabolic and immune components. Evidence has accumulated that insulin resistance, energy failures, and inflammation in the brain increase the vulnerability of dopaminergic neurons: mitochondria are disrupted, oxidative stress increases, microglia are activated, and the aggregation of α-synuclein, the PD "signature" protein, is facilitated. These links link metabolic health with neurodegeneration and set a clear preventive vector: by improving metabolism, we potentially weaken the "soil" for PD.

In general medicine, metabolic syndrome (MetS) is one of the main markers of ill-being. According to the NCEP ATP III criteria, it is diagnosed with a combination of ≥3 of five components: abdominal obesity, high blood pressure, hyperglycemia/insulin resistance, high triglycerides, and low HDL cholesterol. MetS itself increases cardiovascular risks, but neurologists are increasingly interested precisely because this “package” of factors is modifiable: unlike age-related vulnerability or genetics, it can be specifically corrected by lifestyle and therapy.

Recent epidemiology supports the “metabolic ↔ PD” link. Meta-analyses report an increased risk of PD in people with type 2 diabetes and, to a lesser extent but still detectable, in prediabetes; some studies show that MetS itself is associated with a higher probability of incident Parkinson’s. Biologically, this is consistent with the idea of an “insulin-resistant brain” and is complemented by data on the gut-brain axis: dysbiotic shifts characteristic of cardiometabolic disorders can increase neuroinflammation and promote pathology along the “gut → brain” axis.

Against this background, a new prospective study in Neurology has become one of the largest tests of the hypothesis on “large numbers”: during an observation period of ≈15 years in 467 thousand participants, the presence of MetS was associated with an approximately 40% higher risk of a subsequent diagnosis of PD; a meta-analysis combined with previous studies gave a final estimate of ≈+29%. In practice, this means a simple thing: control of body weight, blood pressure, glycemia and lipids is not only about the heart and blood vessels, but also the potential for neuroprophylaxis, especially in people with a hereditary predisposition to PD.

What is metabolic syndrome and why is it important for the brain

MetS is a “package” of mutually reinforcing risk factors for cardiometabolic diseases. By definition, it is three or more of the following:

• abdominal obesity (excess waist size);
• high blood pressure;
• hyperglycemia (high fasting blood sugar/impaired glucose regulation);
• high triglycerides;
• low HDL cholesterol ("good" cholesterol).

The authors emphasize that metabolic health is modifiable, which is why finding a link to Parkinson's risk is important from a prevention and public health perspective. News-Medical

How It Was Studied: Design, Amendments, and Independent Review

The study was based on a large prospective database with long-term follow-up. The baseline exposure was the presence of MetS, the outcome was incident Parkinson's disease; regression models were adjusted for age, smoking, physical activity level, and Parkinson's polygenic risk (genetic predisposition). Key figures: 38% of participants had MetS at baseline; 3,222 new cases of Parkinson's were registered during the follow-up period; the relative risk in the MetS group was ~1.4 (≈+40%). To ensure that the signal was not unique to this cohort, the researchers conducted a meta-analysis of all available studies on the topic: the pooled estimate showed a +29% increase in risk in people with MetS.

What this means in practice: lessons for prevention

The connection does not prove causality, but it sets a vector of actions that are in themselves useful both cardiologically and neurologically:

• Reducing visceral fat: calorie deficit + moderate-intensity aerobic activity and strength training 2-3 times a week.
• Monitoring blood pressure, sugar and lipids: regular measurements, lifestyle modifications and (if indicated) drug therapy.
• Metabolism Diet: Less ultra-processed foods and sugars, more vegetables, whole grains, legumes, nuts, fish.
• Early work with prediabetes and dyslipidemia: the earlier the MetS components are corrected, the less “background” for vascular and neurodegenerative risks.

The authors separately note that the combination of MetS + an unfavorable genetic profile is associated with an even higher risk of Parkinson's - that is, maintaining metabolic health may be especially important for people with an increased genetic predisposition.

Where to be cautious: limitations and open questions

This is an observational study—it finds associations, not causation. The sample was predominantly white, so the generalizability of the results to other populations requires testing. Finally, the MetS is a graveyard of confounding factors (ranging from socioeconomics to access to care), and even with careful adjustments, residual confounding is possible. However, the consistency of the results with independent summaries and professional press materials strengthens the conclusions.

Context: how the new result fits into the field

Systematic reviews in recent years have suggested a possible link between components of the MetS (hyperglycemia, obesity, hypertension, dyslipidemia) and Parkinson’s risk, but the results have been uneven. The new work adds the largest cohort assessment to date with a long follow-up and highlights an important detail: risk modification by genetics. It argues for an interdisciplinary focus on “metabolic health for brain health.”

Study source: Zhang X. et al. Metabolic Syndrome and Incidence of Parkinson Disease. Neurology, published August 20, 2025; DOI: 10.1212/WNL.0000000000214033.