Functional Connectivity Differences of the Olfactory Network in Parkinson's Disease, Mild Cognitive Impairment and Cognitively Normal Individuals: A Resting-State FMRI Study

1. BackgroundOlfactory dysfunction is an early sign of Parkinson's Disease (PD) and Alzheimer's Disease (AD). A decreased sense of smell is also present in physiological aging and Mild Cognitive Impairment (MCI), but the relationship of olfaction loss with functional connectivity (FC) of olfactory-related regions remain unclear. We utilized resting state functional Magnetic Resonance Imaging (rs-fMRI), with linear and algorithmic associations, to identify olfactory network FC differences that may be representative of cognitive impairment of PD-CogImp and MCI.2. Experimental Procedures104 subjects were recruited from the Center for Neurodegeneration and Translational Neuroscience: 29 cognitively normal (CN; 62.1% women, mean age = 70.48 ± 6.28); 43 MCI (34.9% women, mean age = 73.88 ± 5.63), and 32 PD-CogImp (43.8% women, mean age = 71.09 ± 8.38). A region-based analysis was performed on a total of 30 ROIs chosen for their known relationships to olfaction. FC, based on Pearson correlations, was calculated for all pairwise combinations of these ROIs.3. ResultsDiagnosis was the most important predictor for olfaction across all the ROIs. A significantly lowered FC was observed in the PD-CogImp group. Significantly lower interhemispheric connection between the right middle cingulate cortex and the left medial orbital frontal cortex characteristic to PD was the only FC identified by both approaches.4. DiscussionA distinct olfactory functional network pattern may represent a change involved in PD, warranting further investigation. FC of the olfactory network highlights the potential of such measures in identifying pathophysiological mechanisms, with potential role in the diagnostic process.