Noyce · Annals of neurology 2012 · systematic review and meta-analysis · n=?

Meta-analysis of early nonmotor features and risk factors for Parkinson disease.

Cited 781 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of observational studies evaluating risk factors and prodromal symptoms

PubMed 23071076 · doi:10.1002/ana.23687 · record verified 2026-08-30

What was done

A systematic review and meta-analysis of observational studies evaluating risk factors and early nonmotor symptoms amenable to population-based screening for later diagnosis of Parkinson disease (PD).

What was found

The strongest positive associations with a subsequent PD diagnosis were having any relative with PD (OR 4.45, 95% CI 3.39–5.83), a first-degree relative with PD (OR 3.23, 95% CI 2.65–3.93), any relative with tremor (OR 2.74, 95% CI 2.10–3.57), and a history of constipation (RR 2.34, 95% CI 1.55–3.53). Current smoking was inversely associated with PD compared to never smoking (RR 0.44, 95% CI 0.39–0.50). Additional significant positive associations included anxiety or depression, pesticide exposure, head injury, rural living, farming, well-water drinking, and beta-blocker use. Inverse associations were identified for coffee drinking, hypertension, NSAIDs, calcium channel blockers, alcohol, and elevated serum urate. No significant associations were found for diabetes, cancer, oral contraceptives, hormone replacement therapy, surgical menopause, statins, aspirin, acetaminophen, tea drinking, general anesthesia, or gastric ulcers.

Why it matters

This study consolidates quantitative effect estimates across environmental, clinical, and familial risk markers, highlighting potential targets for early screening protocols and risk-stratification models for PD.

Limits

The abstract does not disclose the number of included studies, total sample size, or degree of statistical heterogeneity across analyses. Included studies were observational, which limits causal inference, and residual confounding or reverse causation (e.g., prodromal symptoms versus true risk factors) cannot be ruled out.

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