Abstract: BACKGROUND: Olfactory dysfunction is an early biological marker of various diseases. However, the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear.
OBJECTIVE: To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson’s disease, and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. 
METHODS: Neuropsychological and olfactory tests, high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease, 44 healthy controls and 29 patients with Parkinson’s disease. DPABI, SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation, regional homogeneity and functional connectivity values between the cerebral small vessel disease, control and Parkinson’s disease groups. Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. 
RESULTS AND CONCLUSION: Compared with the control group, low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson’s disease groups. The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points. Compared with the Parkinson’s disease group, the functional connectivity values of the right anterior cunei, inferior temporal gyrus, anterior central gyrus and dorsolateral superior frontal gyrus, left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups. The left cuneiform lobe was the seed point. Compared with the control group, the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson’s disease groups. The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson’s disease group, and that was enhanced in the cerebral small vessel disease group compared with the Parkinson’s disease group. Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group, and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score, while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson’s disease group was positively correlated with the olfactory recognition score, and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score, respectively. The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson’s disease. The olfactory function of patients with cerebral small vessel disease is related to cognitive function. It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction, while olfactory dysfunction following Parkinson’s disease is directly caused by abnormal function of olfactory-related brain areas. Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

Key words: resting-state functional magnetic resonance imaging, cerebral small vessel disease, olfactory function, cognition, functional connectivity