Olfactory Network Functional Connectivity as a Marker for Parkinson’s Disease Severity

Olfactory impairment was assessed in akinetic-rigid (PD_AR) and tremor-predominant (PD_T) subtypes of Parkinson's disease (PD), classified based on motor symptoms. Seventeen PD_AR, fifteen PD_T, and twenty-four cognitively normal (CN) participants completed the University of Pennsylvania Smell Identification Test (UPSIT). Groups were well-matched for age and demographic variables, with cognitive performance statistically controlled. Resting-state fMRI (rs-fMRI) and seed-based functional connectivity (FC) analyses were conducted to characterize olfactory network (ON) connectivity across groups. UPSIT scores were significantly lower in PD_AR compared to PD_T. Consistently, ON FC values were reduced in PD_AR relative to both PD_T and CN. FC of the primary olfactory cortex (POC) significantly differed between CN and the PD subtypes. Furthermore, connectivity in the orbitofrontal cortex and insula showed significant differences between PD_AR and PD_T, as well as between PD_AR and CN. Notably, ON FC between the left hippocampus and the posterior cingulate cortex (PCC) also differed significantly between PD_AR and PD_T. These findings reveal distinct ON FC patterns across PD_AR and PD_T subtypes. Variations in UPSIT scores suggest that motor symptom subtype is associated with olfactory performance. Moreover, ON connectivity closely paralleled the UPSIT scores, reinforcing a neural basis for olfactory deficits in PD. Given the accelerated motor and cognitive decline often observed in the PD_AR, these results support the potential of olfactory impairment as a clinical marker for disease severity.