A recent American Journal of Epidemiology study reviewed the literature on metal exposure and Parkinson's disease (PD) risk. The goal was also to examine the quality of the overall studies and the exposure assessment methods used.
Study: Metal exposure and risk of Parkinson’s disease: a systematic review and meta-analysis. Image Credit: JneValokuvaus/Shutterstock.com
Background
Parkinson's disease is the second most frequent neurodegenerative disease. It is characterized by muscular rigidity and movement dysfunctions, including bradykinesia, postural instability, and rest tremor. Research has shown that metal exposure could be a potential environmental risk factor for PD.
The overall incidence of PD is around 14 per 100,000 people, but this number rises sharply to 160 per 100,000 people in the above 65 age group. PD is characterized by the selective degeneration of dopaminergic neurons in the Lewy body inclusions and substantia nigra pars compacta.
This leads to dopamine deficiency and motor defects. Globally, PD is showing faster growth than any other neurological disorder, and the rise in the aging population cannot fully explain it.
Recent scientific opinion is that an interaction between genetic and environmental factors causes PD. Over 90% of cases are sporadic, and only a small proportion of PD patients show causative genetic mutations. Among the environmental factors, metal exposure is a key concern.
Metals could lead to oxidative stress and mitochondrial dysfunction, activation of microglial cells and inflammation, or promotion of α-synuclein aggregation and fibril formation. Numerous studies on PD risk and specific metals have been published, but the results are inconclusive.
About the study
The current study aimed to conduct a meta-analysis and systematic review to analyze epidemiological evidence of associations between PD risk and metal exposure.
Specific attention was paid to the exposure assessment methods and the quality of the studies.
The PubMed, EMBASE, and Cochrane databases were searched, five cohort studies and 83 case-control studies were included. The studies were published during 1963-2020. Seventy-three studies were graded as low or moderate overall quality.
Further, 69 studies used biomonitoring and self-reported exposure after disease diagnosis for exposure assessment (EA) approaches.
The Newcastle-Ottawa Scale (NOS) was adapted separately for cohort and case-control studies. The four parameters used to evaluate methodological quality were comparability of the groups, subject selection, ascertainment of either exposure or outcome, and statistical analysis.
Key insights
It was observed that most case-control studies were of moderate quality and were biomonitoring studies. Overall, no consistent associations, except for lead, regarding most metals were observed.
There was a possible increased risk of PD following lead exposure. This was inferred based on two studies where a higher level of lead was observed in the bones of PD patients.
The risk of PD was higher after exposure to airborne mercury, and the mortality was also higher among individuals drinking water with high selenium concentrations.
Some studies showed that excessive metals, such as manganese, iron, lead, mercury, aluminum, and cadmium, could induce injury in dopaminergic neurons.
The role of metals such as zinc and copper remains unclear, whereas magnesium is expected to be a neuroprotective agent.
Limitations of existing studies
It was difficult to draw firm conclusions due to the lack of consistency among studies and the high between-study heterogeneity.
This heterogeneity could have stemmed from different metal detection methods in biomonitoring studies or other factors like age and gender.
The methodological limitations in existing research could introduce significant bias in estimating the association between PD risk and metal exposure. Selection bias cannot be ruled out as some studies identified PD through health care registers or death certificates.
The former is likely to omit early or mild PD cases, therefore, focusing only on severe cases. Further, the selection of controls is also often hospital-based, which may not represent the population.
Lastly, self-reported information could be affected by the awareness of disease status. This could lead to differential recall between the treated and the control groups.
Conclusions
The authors claim that the current study is the first meta-analysis and systematic review to assess the relationship between metal exposure from various routes and the risk of PD.
A huge percentage of research was of poor quality, with high heterogeneity in results and methodological limitations.
This underscores the need for more quality research on PD epidemiology to establish the association between PD risk and metal exposure.
Large prospective cohort studies must have a long follow-up period, comprehensive lifelong exposure history, and well-established biobanks.
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