Wen Zhang1, Jilei Zhang2, and Bing Zhang1
1Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China, 2Philips Healthcare, Shanghai, China, Shanghai, China
Synopsis
Patients with type 2 diabetes mellitus
(T2DM) often have pathologically altered lipid metabolism. Evidence has confirmed
that dyslipidemia is linked to cognitive decline. We explored the large-scale functional
network connectivity alterations and their potential relationships with serum
lipids and cognitive performance in T2DM patients. Our results suggested lower inter
and intra-network functional connectivity in T2DM patients and the possibility
of improving cognitive function through lipids management.
Introduction
Patients with type 2 diabetes mellitus
(T2DM) often have pathologically altered lipid metabolism1. A large
of cross-sectional and longitudinal studies have confirmed that serum lipid
profile is linked to several aspects of human cognition2,3. However,
the brain is a complex system consisting of several functional networks, so
far, little is known about the relationships between lipid metabolism and inter
and intra-network functional connectivity. Our objective was to assess the serum
lipids, cognitive performance, and intra and inter-network functional
connectivity (FC) in T2DM patients Methods
A total of 147 age, sex and education
matched participants were included, divided into T2DM patients with mild
cognitive impairment (T2MCI) (n=40), T2DM patients without mild cognitive
impairment (T2noMCI) (n=62) and 45 normal control subjects. Each participant underwent
resting-state functional MRI scans, cognitive and peripheral blood biochemistry
assessments. Large-scale inter and intra- network FCs were calculated using
independent component analysis. Multivariate analysis of covariance, partial correlation,
and mediation analyses was conducted to test for potential associations between
lipid metabolism, inter and intra-network FC, and cognitive performance. Results
Compared with control subjects, the inter
and intra-network FC were reduced in either T2MCI or T2noMCI patients. We found
significant differences in inter-network FC among the three groups after
adjusted age, sex, education and head motion parameters: between ventral
attention and medial visual networks, between left frontoparietal and posterior
visual networks. In patients with T2DM, lower inter-network FCs were correlated
with higher serum total cholesterol, high-density lipoprotein cholesterol, and low-density
lipoprotein cholesterol, while correlated with worse cognitive performance. Voxel-wise
intra-network FC analyses demonstrated significant group differences in the
left posterior cingulate gyrus of the anterior default mode network, right
middle occipital gyrus of the dorsal attention network, and right superior
parietal lobe of the lateral visual network. Each of these intra-network FC
alterations was positively correlated with MoCA scores in patients with T2DM. More
importantly, the relationship between lipid metabolism scores and cognitive
scores was mediated by the inter-network FC scores.Conclusion
Our current study expands existing knowledge
in type 2 diabetes regarding lipid metabolism-brain-cognition relations from the
perspective of large-scale functional network organization. Our results suggested
the possibility of improving cognitive function through regulating serum lipids
in diabetic patients. Acknowledgements
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