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      Resting-State Brain Networks in Type 1 Diabetic Patients With and Without Microangiopathy and Their Relation to Cognitive Functions and Disease Variables

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          Abstract

          Cognitive functioning depends on intact brain networks that can be assessed with functional magnetic resonance imaging (fMRI) techniques. We hypothesized that cognitive decrements in type 1 diabetes mellitus (T1DM) are associated with alterations in resting-state neural connectivity and that these changes vary according to the degree of microangiopathy. T1DM patients with (MA +: n = 49) and without (MA : n = 52) microangiopathy were compared with 48 healthy control subjects. All completed a neuropsychological assessment and resting-state fMRI. Networks were identified using multisubject independent component analysis; specific group differences within each network were analyzed using the dual-regression method, corrected for confounding factors and multiple comparisons. Relative to control subjects, MA patients showed increased connectivity in networks involved in motor and visual processes, whereas MA + patients showed decreased connectivity in networks involving attention, working memory, auditory and language processing, and motor and visual processes. Better information-processing speed and general cognitive ability were related to increased degree of connectivity. T1DM is associated with a functional reorganization of neural networks that varies, dependent on the presence or absence of microangiopathy.

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          The prevalence of comorbid depression in adults with diabetes: a meta-analysis.

          To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used chi(2) statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8-2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.
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            Resting-state functional connectivity in neuropsychiatric disorders.

            This review considers recent advances in the application of resting-state functional magnetic resonance imaging to the study of neuropsychiatric disorders. Resting-state functional magnetic resonance imaging is a relatively novel technique that has several potential advantages over task-activation functional magnetic resonance imaging in terms of its clinical applicability. A number of research groups have begun to investigate the use of resting-state functional magnetic resonance imaging in a variety of neuropsychiatric disorders including Alzheimer's disease, depression, and schizophrenia. Although preliminary results have been fairly consistent in some disorders (for example, Alzheimer's disease) they have been less reproducible in others (schizophrenia). Resting-state connectivity has been shown to correlate with behavioral performance and emotional measures. It's potential as a biomarker of disease and an early objective marker of treatment response is genuine but still to be realized. Resting-state functional magnetic resonance imaging has made some strides in the clinical realm but significant advances are required before it can be used in a meaningful way at the single-patient level.
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              Selective changes of resting-state networks in individuals at risk for Alzheimer's disease.

              Alzheimer's disease (AD) is a neurodegenerative disorder that prominently affects cerebral connectivity. Assessing the functional connectivity at rest, recent functional MRI (fMRI) studies reported on the existence of resting-state networks (RSNs). RSNs are characterized by spatially coherent, spontaneous fluctuations in the blood oxygen level-dependent signal and are made up of regional patterns commonly involved in functions such as sensory, attention, or default mode processing. In AD, the default mode network (DMN) is affected by reduced functional connectivity and atrophy. In this work, we analyzed functional and structural MRI data from healthy elderly (n = 16) and patients with amnestic mild cognitive impairment (aMCI) (n = 24), a syndrome of high risk for developing AD. Two questions were addressed: (i) Are any RSNs altered in aMCI? (ii) Do changes in functional connectivity relate to possible structural changes? Independent component analysis of resting-state fMRI data identified eight spatially consistent RSNs. Only selected areas of the DMN and the executive attention network demonstrated reduced network-related activity in the patient group. Voxel-based morphometry revealed atrophy in both medial temporal lobes (MTL) of the patients. The functional connectivity between both hippocampi in the MTLs and the posterior cingulate of the DMN was present in healthy controls but absent in patients. We conclude that in individuals at risk for AD, a specific subset of RSNs is altered, likely representing effects of ongoing early neurodegeneration. We interpret our finding as a proof of principle, demonstrating that functional brain disorders can be characterized by functional-disconnectivity profiles of RSNs.
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                Author and article information

                Journal
                Diabetes
                Diabetes
                diabetes
                diabetes
                Diabetes
                Diabetes
                American Diabetes Association
                0012-1797
                1939-327X
                July 2012
                15 June 2012
                : 61
                : 7
                : 1814-1821
                Affiliations
                [1] 1Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
                [2] 2Diabetes Psychology Research Group/Department of Medical Psychology, VU University Medical Center, Amsterdam, the Netherlands
                [3] 3Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands
                [4] 4Department of Anatomy and Neuroscience, VU University Medical Center, Amsterdam, the Netherlands
                [5] 5Department of Radiology, Centro de Investigación y Terapias Avanzadas (CITA)-Alzheimer Foundation, San Sebastian, Spain
                [6] 6Department of Ophthalmology, VU University Medical Center, Amsterdam, the Netherlands
                [7] 7Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
                Author notes
                Corresponding author: Eelco van Duinkerken, e.vanduinkerken@ 123456vumc.nl .
                Article
                1358
                10.2337/db11-1358
                3379683
                22438575
                7ef70217-7a42-4c93-904e-7b13250b1f76
                © 2012 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 29 September 2011
                : 09 February 2012
                Categories
                Complications

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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