Is education a risk factor for Parkinson's disease?: A systematic review and meta-analysis

Parkinson's disease (PD), a prevalent neurodegenerative disease, has shown a twofold increase in global prevalence over the past 25 years, making research into its causes pivotal. Curiously, higher educational attainment has often been linked to a higher risk of PD. Yet, to our knowledge, these findings have not been validated in a systematic literature review and meta-analysis. Thus, we aimed to evaluate the cumulative evidence for such a link and explore potential sources of heterogeneity in effect size estimates. We systematically searched PubMed, Psychinfo, Web of Science and Embase and performed extensive citation and similar article searches. Eligible studies included reports of non-interventional quantitative studies that assessed the association between formal education and the risk of idiopathic PD in human adults. Furthermore, we included studies that evaluated the association between educational level and PD symptom severity as a predefined secondary outcome. For the primary outcome, we performed a random-effects meta-analysis to synthesise the effect of education on PD risk. The secondary outcome was synthesised qualitatively. We conducted multiple a priori subgroup analyses to investigate potential causes of heterogeneity. Risk of bias of included studies was assessed using the QUIPS tool. This study was prospectively registered on PROSPERO, (ID: CRD420250651033). Of 23,648 identified reports, 36 papers met inclusion criteria. The majority of these studies were assessed as having moderate or high overall risk of bias. Meta-analytic findings yielded a non-significant association between formal educational attainment and risk of PD, with a pooled odds ratio (OR) of 1.09 (k = 24; 95% CI: 0.92 - 1.28). Sensitivity analyses excluding outliers yielded similar results. Subgroup analyses did not explain observed heterogeneity in the results. There was no evidence of small study effects or p-hacking. Education appeared to be associated with reduced PD symptom severity but the number and quality of studies was limited. Education is unlikely to be an independent risk factor for PD. Study heterogeneity and methodological limitations preclude firm conclusions, though. Future research should investigate if healthcare access or literacy underly any associations of education and PD. The most plausible explanation for the apparent link between the two is lacking control for multiple comparisons and a distorted discussion of the results of analyses. Funding was provided by the UK Medical Research Council and the German Academic Scholarship Foundation.