Associations between olfactory dysfunction and structural MRI findings in Parkinson's disease: a systematic review

Clinical Snapshot

Key Findings

• P Value: Not reported at the review level; individual study statistics not synthesised

• Effect Size: Not reported; narrative synthesis only — no pooled effect sizes calculated

• Primary Outcome: Structural MRI changes associated with olfactory dysfunction in Parkinson's disease, identified across olfactory sulcus, olfactory bulb, cortical grey matter, hippocampus, parahippocampus, and basal ganglia

• Nnt Or Sensitivity: Not applicable; no diagnostic accuracy meta-analysis performed. Structural MRI findings are proposed as potential early biomarkers but sensitivity and specificity are not calculated at the review level

• Confidence Interval: Not reported; no meta-analysis performed

Clinical Application

Structural MRI is widely available in Australian tertiary and many secondary care settings. However, the lack of standardised MRI protocols and olfactory assessment tools identified in this review means that routine clinical application as a diagnostic or prognostic biomarker is not yet feasible. Implementation would require consensus on MRI acquisition parameters and validated olfactory testing protocols. In Australia, PD affects approximately 80,000 individuals, with incidence rising with an ageing population. Olfactory testing is not currently part of standard RACGP or Neurology Society of Australia PD diagnostic guidelines. Structural MRI for PD is available under Medicare (MBS Item 63551 and related items) but is not specifically indicated for olfactory biomarker assessment. No TGA-approved structural MRI biomarker protocol for PD olfactory dysfunction currently exists. The findings of this review are hypothesis-generating and do not yet support changes to Australian clinical practice guidelines. Future Australian longitudinal cohort studies (e.g., through the Australian Parkinson's Mission) could contribute standardised data to address the gaps identified. Adults with established Parkinson's disease diagnosis, particularly those with early or prominent olfactory dysfunction. Potentially applicable to prodromal PD populations where olfactory loss precedes motor symptoms, though this review does not specifically address prodromal cohorts.

Abstract

Olfactory dysfunction is a common and early non-motor symptom of Parkinson's disease (PD). Structural Magnetic Resonance Imaging (MRI) studies have reported changes in olfactory-related brain regions, but findings remain inconsistent. This review synthesizes MRI evidence to clarify neuroanatomical correlates of olfactory dysfunction in PD. We performed a systematic review to find the associations between olfactory dysfunction and structural MRI findings in people with PD. A systematic search in PubMed, Scopus, and Web of Science yielded 20 eligible studies. The eligible studies involved 1,092 patients with PD. Although there were inconsistent regions of interest and types of analysis, we identified structural changes in the olfactory sulcus and bulb, cortical gray matter, hippocampus, parahippocampus, and basal ganglia that are associated with olfactory dysfunction. Olfactory dysfunction in PD is linked to structural changes in primary olfactory, limbic, and cortical regions. These MRI findings may serve as early biomarkers, but standardized, longitudinal studies are needed to confirm their diagnostic or prognostic value.

References

1. 1.Alikhani, Y., Zolfaghari, A., Shahkarami, F., & Seyedmirzaei, H. (2026). Associations between olfactory dysfunction and structural MRI findings in Parkinson's disease: a systematic review. Brain Imaging and Behavior. https://doi.org/10.1111/ene.16041