Wen Zhang1, Jiaming Lu1, Jilei Zhang2, and Bing Zhang1
1Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China, 2Philips Healthcare, Shanghai, China
Synopsis
Type 2 diabetes mellitus (T2DM) is associated
with olfactory dysfunction and cognitive decline. We proposed one functional
connectivity (FC) model that links the primary olfactory cortex (POC) to
advanced cognition related cognitive brain area. The whole olfactory network was
divided into three sub-networks: POC consists of the bilateral anterior
olfactory nucleus, piriform cortex, entorhinal cortex, and amygdala; secondary
olfactory cortex (SOC) include the bilateral hippocampus, parahippocampus,
thalamus, and hypothalamus; advanced olfactory cortex (AOC) consists of
bilateral orbitofrontal cortex, insula and dorsolateral prefrontal
cortex(DLPFC). Our results suggested that FC was heterogeneously disrupted in
the POC-SOC-AOC olfactory pathway in T2DM.
Introduction
Type 2 diabetes mellitus (T2DM) is reported to be
associated with olfactory dysfunction and cognitive decline. However, how
olfactory neural circuit abnormalities involve cognitive impairment in diabetes
remains unclear. To investigate olfactory network alterations and the mediation
of odor perception and cognition in patients with T2DM, we proposed one
functional connectivity (FC) model that links the primary olfactory cortex
(POC) to advanced cognition related cognitive brain area.Methods
108 right-handed T2DM patients (age: 52.3±9.0, 59 male and 49 female) and 58
normal control (age: 54.2±9.6, 26 male and 32 female) were included. Resting-state functional MRI (rs-fMRI) data,
olfactory behavior test score, and cognitive assessment scales were acquired
from each participant. In this study, we applied the region of interest
(ROI)-wise FC analyses to investigate the relationship between POC and
neocortical cognition-related areas. We divided the whole olfactory network
into three sub-networks: POC consists of the bilateral anterior olfactory nucleus,
piriform cortex, entorhinal cortex, and amygdala; secondary olfactory cortex
(SOC) include the bilateral hippocampus, parahippocampus, thalamus, and
hypothalamus; advanced olfactory cortex (AOC) consists of the bilateral
orbitofrontal cortex, insula, and dorsolateral prefrontal cortex(DLPFC). The network analysis was introduced to generate the network pattern and do group
comparison.Results
There were no significant differences in age
(p=0.218), sex (p=0.184), and education (p=0.188) between the two groups.
Compared with the normal control, patients with T2DM demonstrated significantly
lower olfactory threshold score (p=0.002) and decreased cognitive function,
especially in recalled memory (p=0.005) and executive function (p=0.015). In
the normal group, the inner and interconnections in the three sub-networks were
well organized. However, the network integrality was disrupted in T2DM patients.
There were significant decreased FC within and between these three
sub-networks. Notably, the most severe FC decline was within the POC sub-network,
followed by decreased FC between the POC and the SOC, the minimal disruption connections
were between POC and AOC sub-network. Conclusion
The current study found FC was heterogeneously
disrupted in the POC-SOC-AOC olfactory pathway in T2DM, revealed distinct FC
decline between subregions in POC and advanced cognitive brain networks. Our
results suggested that there could be some compensation mechanisms underlying
the progressive disconnection from the primary cortex to the advanced cortex
within the olfactory network. These may help explain cognitive dysfunction and its
progression in diabetes.Acknowledgements
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