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      Altered Functional Hubs and Connectivity in Type 2 Diabetes Mellitus Without Mild Cognitive Impairment

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          Abstract

          Background: Type 2 diabetes mellitus (T2DM)-related cognitive decline is associated with neuroimaging changes. However, only a few studies have focused on early functional alteration in T2DM prior to mild cognitive impairment (MCI). This study aimed to investigate the early changes of global connectivity patterns in T2DM by using a resting-state functional magnetic resonance imaging (rs-fMRI) technique.

          Methods: Thirty-four T2DM subjects and 38 age-, sex-, and education-matched healthy controls (HCs) underwent rs-fMRI in a 3T MRI scanner. Degree centrality (DC) was used to identify the functional hubs of the whole brain in T2DM without MCI. Then the functional connectivity (FC) between hubs and the rest of the brain was assessed by using the hub-based approach.

          Results: Compared with HCs, T2DM subjects showed increased DC in the right cerebellum lobules III–V. Hub-based FC analysis found that the right cerebellum lobules III–V of T2DM subjects had increased FC with the right cerebellum crus II and lobule VI, the right temporal inferior/middle gyrus, and the right hippocampus.

          Conclusions: Increased DC in the right cerebellum regions III–V, as well as increased FC within cerebellar regions and ipsilateral cerebrocerebellar regions, may indicate an important pathophysiological mechanism for compensation in T2DM without MCI.

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          Most cited references42

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          Executive Functions

          Executive functions (EFs) make possible mentally playing with ideas; taking the time to think before acting; meeting novel, unanticipated challenges; resisting temptations; and staying focused. Core EFs are inhibition [response inhibition (self-control—resisting temptations and resisting acting impulsively) and interference control (selective attention and cognitive inhibition)], working memory, and cognitive flexibility (including creatively thinking “outside the box,” seeing anything from different perspectives, and quickly and flexibly adapting to changed circumstances). The developmental progression and representative measures of each are discussed. Controversies are addressed (e.g., the relation between EFs and fluid intelligence, self-regulation, executive attention, and effortful control, and the relation between working memory and inhibition and attention). The importance of social, emotional, and physical health for cognitive health is discussed because stress, lack of sleep, loneliness, or lack of exercise each impair EFs. That EFs are trainable and can be improved with practice is addressed, including diverse methods tried thus far.
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            The economy of brain network organization.

            The brain is expensive, incurring high material and metabolic costs for its size--relative to the size of the body--and many aspects of brain network organization can be mostly explained by a parsimonious drive to minimize these costs. However, brain networks or connectomes also have high topological efficiency, robustness, modularity and a 'rich club' of connector hubs. Many of these and other advantageous topological properties will probably entail a wiring-cost premium. We propose that brain organization is shaped by an economic trade-off between minimizing costs and allowing the emergence of adaptively valuable topological patterns of anatomical or functional connectivity between multiple neuronal populations. This process of negotiating, and re-negotiating, trade-offs between wiring cost and topological value continues over long (decades) and short (millisecond) timescales as brain networks evolve, grow and adapt to changing cognitive demands. An economical analysis of neuropsychiatric disorders highlights the vulnerability of the more costly elements of brain networks to pathological attack or abnormal development.
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              Risk of dementia in diabetes mellitus: a systematic review.

              The relation between diabetes and major types of dementia is controversial. This systematic review examines the incidence of dementia in people with diabetes mellitus. We identified 14 eligible longitudinal population-based studies of variable methodological quality. The incidence of "any dementia" was higher in individuals with diabetes than in those without diabetes in seven of ten studies reporting this aggregate outcome. This high risk included both Alzheimer's disease and vascular dementia (eight of 13 studies and six of nine studies respectively). Detailed data on modulating and mediating effects of glycaemic control, microvascular complications, and comorbidity (eg, hypertension and stroke) were generally absent. The findings of mechanistic studies suggest that vascular disease and alterations in glucose, insulin, and amyloid metabolism underlie the pathophysiology, but which of these mechanisms are clinically relevant is unclear. Further high quality studies need to be initiated, with objective diabetes assessment, together with reliable methods to establish the contribution of vascular disease and other comorbidity to dementia.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                11 September 2020
                2020
                : 11
                : 1016
                Affiliations
                [1] 1First Clinical Medical College, Guangzhou University of Chinese Medicine , Guangzhou, China
                [2] 2Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine , Guangzhou, China
                [3] 3Department of Radiology, The First Affiliated Hospital of Guangdong Pharmaceutical University , Guangzhou, China
                Author notes

                Edited by: Nicola Toschi, University of Rome Tor Vergata, Italy

                Reviewed by: Alessia Sarica, University of Magna Graecia, Italy; Nicola Amoroso, University of Bari Aldo Moro, Italy

                *Correspondence: Shijun Qiu qiu-sj@ 123456163.com

                This article was submitted to Applied Neuroimaging, a section of the journal Frontiers in Neurology

                †These authors have contributed equally to this work

                ‡These authors share first authorship

                Article
                10.3389/fneur.2020.01016
                7533640
                33071928
                36022b2d-aafd-4bc3-800f-a0f178aee165
                Copyright © 2020 Li, Liang, Tan, Chen, Yang, Zeng, Qin, Feng, Ma and Qiu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 May 2020
                : 03 August 2020
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 55, Pages: 9, Words: 6332
                Funding
                Funded by: National Science Foundation of China 10.13039/501100001809
                Award ID: 81771344
                Award ID: 91649117
                Award ID: 81920108019
                Categories
                Neurology
                Original Research

                Neurology
                type 2 diabetes mellitus,resting state,functional connectivity,degree centrality,cognitive function

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