Hemispheric lateralization of dopamine transporter binding in Parkinson's disease

Asymmetries in dopaminergic depletion between the right and left cerebral hemispheres could provide insights about the development and progression of cerebral neurodegeneration in Parkinson's disease. We investigated whether more patients with Parkinson's disease exhibited lower left than right dopamine radiotracer binding in two large cohorts.

This cross-sectional study retrospectively analyzed consecutive ¹⁸F-FE-PE2I PET scans conducted at the Department of Nuclear Medicine and PET, Aarhus University Hospital, Denmark, from May 2020 to December 2024 (Aarhus dataset, n = 1257). Findings were compared with an international, multicenter, research cohort (PPMI dataset, n = 1359).

A slim majority (53 %) of patients had lower binding in the left putamen than in the right (Aarhus dataset: P = 0.0803; PPMI dataset: P = 0.0466; two tailed-binomial test). This difference was driven by patients with higher levels of asymmetry and remained consistent across age, sex, and disease duration, and was not observed in healthy controls. Based on handedness, there was a marginal majority of patients with lower dopamine tracer binding in the dominant hemisphere, which was significant among right-handed (53 %, P = 0.0160) but not among left-handed (54 %, P = 0.3071). These trends were supported by our models, indicating that handedness explained very little of the variance in hemispheric lateralization.

The predominance of lower dopamine binding in the dominant hemisphere is narrow and only marginally significant, even in large datasets. Our estimates are more modest compared to those previously reported, possibly because we did not exclude symmetric patients.