Exposure to macrocyclic GBCAs does not increase Parkinson’s risk

Patient exposure to linear gadolinium-based contrast agents (GBCAs) may marginally increase the risk of parkinsonism in adults, but exposure to macrocyclic GBCAs doesn’t appear to, researchers have reported.

The findings suggest that “until further evidence emerges, caution should be exercised when using linear GBCAs,” wrote a team led by Na-Young Shin, MD, of Yonsei University College of Medicine in Seoul, Korea. The group’s results were published February 3 in the Korean Journal of Radiology.

Researchers have been concerned about the effects of GBCAs on patient health for many years, particularly whether gadolinium contributes to nephrogenic systemic fibrosis (NSF) and whether it remains in the brain after imaging. Previous studies have reported no link between gadolinium and parkinsonism, but other research has found differences in gadolinium deposits depending on the type of GBCA.

Shin and colleagues investigated the influence of GBCA exposure on the development of parkinsonism according to the GBCA type via a study that included 222,977 patients aged 40 years or older who underwent first-ever MRI examinations between 2011 and 2014 and were tracked through 2022. Study participants were divided into two groups: those who had at least one GBCA-enhanced MRI exam and those who had only nonenhanced MR imaging (n = 92,230). Individuals who were exposed to GBCA were further categorized into those exposed to linear or macrocyclic agents (n = 48,335 and n = 82,412, respectively).

The primary outcome for the study was the incidence of all-cause parkinsonism, while secondary outcomes included all-cause parkinsonism requiring medication, Parkinson’s disease, atypical Parkinsonism, and secondary parkinsonism. The team estimated hazard ratios for all of these, focusing on patient exposure to linear and macrocyclic GBCAs — with the nonenhanced MRI group as reference — and adjusting for age, sex, smoking status, alcohol use, regular exercise, body mass index, estimated glomerular filtration rate, and comorbidities.

Overall, the group found that exposure to linear GBCAs slightly increased the risk of all-cause parkinsonism, while exposure to macrocyclic GBCAs did not increase the risk. It also reported that these results were similar for all-cause parkinsonism requiring medication, Parkinson’s disease, and secondary parkinsonism, but that there was no significant association for atypical parkinsonism.

In an accompanying editorial, Won-Jin Moon, MD, PhD, of Konkuk University Medical Center in Seoul wrote that the study offers “significant implications for the management of MRI examinations,” noting that “in clinical practice, we must ensure that neither patients nor physicians are burdened by ‘gadolinium phobia.'”

“The findings reinforce the message that the use of macrocyclic GBCAs appears safe regarding parkinsonism risk,” she wrote. “Furthermore, the weak association observed with linear GBCAs should not be immediately interpreted as clear causality. Instead, it warrants a cautious interpretation and calls for more elaborate, prospective research to disentangle these complex confounders.”

Access the full study here.