Structural and functional connectomics of the olfactory system in Parkinson's disease: a systematic review

Olfactory dysfunction, affecting 75–90 % of Parkinson's disease (PD) patients, holds significant predictive value for PD development. Advanced imaging techniques, such as diffusion MRI (dMRI) and functional MRI (fMRI), offer insights into structural and functional changes within olfactory pathways. This review summarizes a decade of research on MRI-based connectivity of the olfactory system in PD, focusing on structural and functional alterations in olfactory brain areas and their links to early olfactory processing changes. Fifteen dMRI and eighteen fMRI studies met inclusion criteria and were carefully reviewed. Among the studies investigating diffusion metrics, the most consistent finding was the reduction of fractional anisotropy in the olfactory tract and anterior olfactory structures, though evidence correlating this result to olfactory dysfunction is limited and contrasting. dMRI support the hypothesis that olfactory function may be correlated to structural alterations at the network-level. In contrast, fMRI studies found more consistent evidence of dysconnectivity in both primary and secondary olfactory areas as directly correlated to olfactory processing and dysfunction. Results suggest a potential dissociation between structural alterations in olfactory brain regions and early functional impairment in olfactory processing, likely related to different patient subtypes. Heterogeneity in clinical and technical factors may limit the generalizability of the results, leaving room for further investigations. By providing a comprehensive perspective on the use of dMRI and fMRI to explore the olfactory connectome in PD, our review might facilitate future research towards earlier diagnosis and more targeted therapeutic and neurorehabilitation strategies.