Objective: Olfactory dysfunction is highly prevalent and often precedes motor symptoms, making it a potential early biomarker for disease progression and cognitive decline in Parkinson’s disease (PD).
Background: This study aimed to investigate the relationship between olfactory dysfunction, cognitive decline, and genetic variants in PD using data from578 PPMI database and 172 PD patients from Ruijin (RJ) cohorts.
Method: Olfactory function was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) and Sniffin’ Sticks 16-item test (SS-16). Genetic analysis focused on PD-related SNPs, while neuroimaging was performed using voxel-based morphometry (VBM) on MRI data, and dopamine transporter (DAT) SPECT imaging. Structural equation modeling (SEM) was employed to explore the relationships between genetic variants, brain imaging metrics, olfactory function, and cognitive performance.
Results: Our findings showed that olfactory dysfunction was associated with an increased risk of cognitive decline in both cohorts, with patients exhibiting anosmia demonstrating a significantly higher likelihood of cognitive impairment at follow-up (PPMI: P = 0.00012; RJ: P = 0.017). Genetic analysis identified a significant associations between olfactory dysfunction and the rs8005172 SNP of GALC (dominant model: OR = 2.27, P = 0.027; recessive model: OR = 5.58, P = 0.007). Neuroimaging showed gray matter atrophy in the right superior temporal pole (STP) among GALC variant carriers (P < 0.001). SEM analysis indicated that the GALC genotype directly influenced olfactory function (path coefficient = -0.2, P < 0.01) and indirectly affected cognitive performance through changes in brain structure (path coefficient = -0.339, P < 0.001).
Conclusion: In conclusion, olfactory dysfunction serves as a potential early biomarker for cognitive decline in PD, and specific genetic variants in GALC may contribute to both olfactory and cognitive impairments. Integrating genetic, clinical, and neuroimaging data offers insights into the mechanisms linking these factors. Future research should validate these findings in larger, diverse cohorts and explore interventions to mitigate effects.
To cite this abstract in AMA style:
Y. Li, M. Zhong, J. Liu. Multimodal Dissection of GALC Variants Linking Olfactory Deficits to Cognitive Decline in Parkinson’s Disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/multimodal-dissection-of-galc-variants-linking-olfactory-deficits-to-cognitive-decline-in-parkinsons-disease/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/multimodal-dissection-of-galc-variants-linking-olfactory-deficits-to-cognitive-decline-in-parkinsons-disease/