Olfactory performance and resting state functional connectivity in non-demented drug naïve patients with Parkinson's disease

Olfactory performance in Parkinson's disease (PD) is closely associated with subsequent cognitive decline. In the present study, we analyzed the olfaction-dependent functional connectivity with a hypothesis that olfactory performance would influence functional connectivity within key brain areas of PD. A total of 110 nondemented drug-naïve patients with PD were subdivided into three groups of high score (PD-H, n=23), middle score (PD-M, n=64), and low score (PD-L, n=23) based on olfactory performance. We performed the resting-state functional connectivity with seed region of interest in the posterior cingulate cortex (PCC) and caudate. An analysis of functional connectivity revealed that PD-L patients exhibited a significant attenuation of cortical functional connectivity with the PCC in the bilateral primary sensory areas, right frontal areas, and right parietal areas compared to PD-H or PD-M patients. Meanwhile, PD-L patients exhibited a significant enhancement of striatocortical functional connectivity in the bilateral occipital areas and right frontal areas compared to PD-H or PD-M patients. In the voxel-wise correlation analysis, olfactory performance was positively associated with cortical functional connectivity with the PCC in similar areas of attenuated cortical connectivity in PD-L patients relative to PD-H patients. On the other hand, the cortical functional connectivity with the caudate was negatively correlated with olfactory performance in similar areas of increased connectivity in PD-L patients relative to PD-H patients. The present study demonstrated that resting state functional connectivity exhibits a distinctive pattern depending on olfactory performance, which might shed light on a meaningful relationship between olfactory impairment and cognitive dysfunction in PD.