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Yang Y, Zhao B, Wang Y, Lan H, Liu X, Hu Y, Cao P. Diabetic neuropathy: cutting-edge research and future directions. Signal Transduct Target Ther 2025; 10:132. [PMID: 40274830 PMCID: PMC12022100 DOI: 10.1038/s41392-025-02175-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 12/12/2024] [Accepted: 02/08/2025] [Indexed: 04/26/2025] Open
Abstract
Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes mellitus, significantly impacting patient quality of life and contributing to morbidity and mortality. Affecting approximately 50% of patients with diabetes, DN is predominantly characterized by distal symmetric polyneuropathy, leading to sensory loss, pain, and motor dysfunction, often resulting in diabetic foot ulcers and lower-limb amputations. The pathogenesis of DN is multifaceted, involving hyperglycemia, dyslipidemia, oxidative stress, mitochondrial dysfunction, and inflammation, which collectively damage peripheral nerves. Despite extensive research, disease-modifying treatments remain elusive, with current management primarily focusing on symptom control. This review explores the complex mechanisms underlying DN and highlights recent advances in diagnostic and therapeutic strategies. Emerging insights into the molecular and cellular pathways have unveiled potential targets for intervention, including neuroprotective agents, gene and stem cell therapies, and innovative pharmacological approaches. Additionally, novel diagnostic tools, such as corneal confocal microscopy and biomarker-based tests, have improved early detection and intervention. Lifestyle modifications and multidisciplinary care strategies can enhance patient outcomes. While significant progress has been made, further research is required to develop therapies that can effectively halt or reverse disease progression, ultimately improving the lives of individuals with DN. This review provides a comprehensive overview of current understanding and future directions in DN research and management.
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Affiliation(s)
- Yang Yang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China.
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
| | - Bing Zhao
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuanzhe Wang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongli Lan
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xinyu Liu
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yue Hu
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Peng Cao
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China.
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
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Aivalioti E, Georgiopoulos G, Tual-Chalot S, Bampatsias D, Delialis D, Sopova K, Drakos SG, Stellos K, Stamatelopoulos K. Amyloid-beta metabolism in age-related neurocardiovascular diseases. Eur Heart J 2025; 46:250-272. [PMID: 39527015 PMCID: PMC11735085 DOI: 10.1093/eurheartj/ehae655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/13/2024] [Accepted: 09/15/2024] [Indexed: 11/16/2024] Open
Abstract
Epidemiological evidence suggests the presence of common risk factors for the development and prognosis of both cardio- and cerebrovascular diseases, including stroke, Alzheimer's disease, vascular dementia, heart, and peripheral vascular diseases. Accumulation of harmful blood signals may induce organotypic endothelial dysfunction affecting blood-brain barrier function and vascular health in age-related diseases. Genetic-, age-, lifestyle- or cardiovascular therapy-associated imbalance of amyloid-beta (Aβ) peptide metabolism in the brain and periphery may be the missing link between age-related neurocardiovascular diseases. Genetic polymorphisms of genes related to Aβ metabolism, lifestyle modifications, drugs used in clinical practice, and Aβ-specific treatments may modulate Aβ levels, affecting brain, vascular, and cardiac diseases. This narrative review elaborates on the effects of interventions on Aβ metabolism in the brain, cerebrospinal fluid, blood, and peripheral heart or vascular tissues. Implications for clinical applicability, gaps in knowledge, and future perspectives of Aβ as the link among age-related neurocardiovascular diseases are also discussed.
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Affiliation(s)
- Evmorfia Aivalioti
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens Medical School, PO Box 11528, 80 Vas. Sofias Str., Athens, Greece
| | - Georgios Georgiopoulos
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens Medical School, PO Box 11528, 80 Vas. Sofias Str., Athens, Greece
- School of Biomedical Engineering and Imaging Sciences, King’s College, London, UK
- Department of Physiology, School of Medicine, University of Patras, Patra, Greece
| | - Simon Tual-Chalot
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Centre for Life, Newcastle Upon Tyne, NE1 3BZ, UK
| | - Dimitrios Bampatsias
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens Medical School, PO Box 11528, 80 Vas. Sofias Str., Athens, Greece
- Division of Cardiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Dimitrios Delialis
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens Medical School, PO Box 11528, 80 Vas. Sofias Str., Athens, Greece
| | - Kateryna Sopova
- Department of Cardiovascular Research, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13–17, D-68167 Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
| | - Stavros G Drakos
- Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI), University of Utah School of Medicine, Salt Lake City, UT, USA
- Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Konstantinos Stellos
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Centre for Life, Newcastle Upon Tyne, NE1 3BZ, UK
- Department of Cardiovascular Research, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13–17, D-68167 Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany
- Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
| | - Kimon Stamatelopoulos
- Department of Clinical Therapeutics, National and Kapodistrian University of Athens Medical School, PO Box 11528, 80 Vas. Sofias Str., Athens, Greece
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Centre for Life, Newcastle Upon Tyne, NE1 3BZ, UK
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Uchida Y, Nishimaki K, Soldan A, Moghekar A, Albert M, Oishi K. Acceleration of Brain Atrophy and Progression From Normal Cognition to Mild Cognitive Impairment. JAMA Netw Open 2024; 7:e2441505. [PMID: 39476236 PMCID: PMC11525609 DOI: 10.1001/jamanetworkopen.2024.41505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 08/27/2024] [Indexed: 11/02/2024] Open
Abstract
Importance It remains unclear which risk factors accelerate brain atrophy along with a progression from normal cognition to mild cognitive impairment (MCI). Objective To examine risk factors associated with the acceleration of brain atrophy and progression from normal cognition to MCI based on long-term longitudinal data for middle-aged and older adults. Design, Setting, and Participants Data for this cohort study were extracted from the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) cohort, initiated at the National Institutes of Health from January 1, 1995, to December 31, 2005, and continued at Johns Hopkins University from January 1, 2015, to October 31, 2023. All participants were cognitively normal at baseline. The participants whose structural magnetic brain imaging (MRI) of the brain and cerebrospinal fluid (CSF) measures were available for over 10 years were included. Exposures Longitudinal structural MRI of the brain and measurement of CSF biomarkers for Alzheimer disease pathology (ratio of amyloid β peptide 42 [Aβ42] to Aβ40, tau phosphorylated at threonine 181, and total tau). Main Outcomes and Measures Annual change rates of segmental brain volumes, Kaplan-Meier survival curves plotting time to event for progression to MCI symptom onset, and hazard ratios (HRs) determined by Cox proportional hazards regression models. Results A total of 185 participants (mean [SD] age, 55.4 [8.4] years; 116 women [63%]) were included and followed up for a maximum of 27 years (median, 20 [IQR, 18-22] years). The groups with high levels of atrophy in the white matter and enlargement in the ventricles had an earlier progression from normal cognition to MCI symptom onset (HR for white matter, 1.86 [95% CI, 1.24-2.49]; P = .001; HR for ventricles, 1.71 [95% CI, 1.19-2.24]; P = .009). Diabetes was associated with progression to MCI (HR, 1.41 [95% CI, 1.06-1.76]; P = .04), as was a low CSF Aβ42:Aβ40 ratio (HR, 1.48 [95% CI, 1.09-1.88]; P = .04), and their combination had a higher HR of 1.55 (95% CI, 1.13-1.98]; P = .03), indicating a synergic association of diabetes and amyloid pathology with MCI progression. Conclusions and Relevance In this cohort study of middle-aged and older adults, higher rates of volume change in the white matter and ventricles, along with the presence of diabetes and a low CSF Aβ42:Aβ40 ratio, were identified as important risk factors for the progression to MCI. These results support the importance of identifying individuals who have accelerated brain atrophy to optimize preventive strategies for progression to MCI.
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Affiliation(s)
- Yuto Uchida
- Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kei Nishimaki
- Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Anja Soldan
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Abhay Moghekar
- The Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Baltimore, Maryland
| | - Marilyn Albert
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kenichi Oishi
- Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
- The Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, Baltimore, Maryland
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Chen Y, Li Z, Chen Y, Dang M, Chen K, Sang F, Fang H, Zhang Z. Cerebellar gray matter and white matter damage among older adults with prediabetes. Diabetes Res Clin Pract 2024; 213:111731. [PMID: 38851538 DOI: 10.1016/j.diabres.2024.111731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 05/16/2024] [Accepted: 06/02/2024] [Indexed: 06/10/2024]
Abstract
AIMS To investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. METHODS The current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. RESULTS Participants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. CONCLUSIONS Cerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes.
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Affiliation(s)
- Yaojing Chen
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China.
| | - Ziyun Li
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China
| | - Yuan Chen
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China
| | - Mingxi Dang
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China
| | - Kewei Chen
- Banner Alzheimer's Institute, Phoenix, AZ 85006, USA
| | - Feng Sang
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China
| | - Hongjuan Fang
- Department of Endocrinology, Civil Aviation General Hospital, Beijing 100012, China
| | - Zhanjun Zhang
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; BABRI Centre, Beijing Normal University, Beijing 100875, China.
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Augustine-Wofford K, Connaughton VP, McCarthy E. Are Hyperglycemia-Induced Changes in the Retina Associated with Diabetes-Correlated Changes in the Brain? A Review from Zebrafish and Rodent Type 2 Diabetes Models. BIOLOGY 2024; 13:477. [PMID: 39056672 PMCID: PMC11273949 DOI: 10.3390/biology13070477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 07/28/2024]
Abstract
Diabetes is prevalent worldwide, with >90% of the cases identified as Type 2 diabetes. High blood sugar (hyperglycemia) is the hallmark symptom of diabetes, with prolonged and uncontrolled levels contributing to subsequent complications. Animal models have been used to study these complications, which include retinopathy, nephropathy, and peripheral neuropathy. More recent studies have focused on cognitive behaviors due to the increased risk of dementia/cognitive deficits that are reported to occur in older Type 2 diabetic patients. In this review, we collate the data reported from specific animal models (i.e., mouse, rat, zebrafish) that have been examined for changes in both retina/vision (retinopathy) and brain/cognition, including db/db mice, Goto-Kakizaki rats, Zucker Diabetic Fatty rats, high-fat diet-fed rodents and zebrafish, and hyperglycemic zebrafish induced by glucose immersion. These models were selected because rodents are widely recognized as established models for studying diabetic complications, while zebrafish represent a newer model in this field. Our goal is to (1) summarize the published findings relevant to these models, (2) identify similarities in cellular mechanisms underlying the disease progression that occur in both tissues, and (3) address the hypothesis that hyperglycemic-induced changes in retina precede or predict later complications in brain.
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Affiliation(s)
| | - Victoria P. Connaughton
- Department of Biology, American University, Washington, DC 20016, USA; (K.A.-W.); (E.M.)
- Center for Neuroscience and Behavior, American University, Washington, DC 20016, USA
| | - Elizabeth McCarthy
- Department of Biology, American University, Washington, DC 20016, USA; (K.A.-W.); (E.M.)
- Center for Neuroscience and Behavior, American University, Washington, DC 20016, USA
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Grashow R, Eagle SR, Terry DP, DiGregorio H, Baggish AL, Weisskopf MG, Kontos A, Okonkwo DO, Zafonte R. Medical Conditions in Former Professional American-Style Football Players Are Associated With Self-Reported Clinical Features of Traumatic Encephalopathy Syndrome. Neurotrauma Rep 2024; 5:376-386. [PMID: 38655114 PMCID: PMC11035840 DOI: 10.1089/neur.2024.0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024] Open
Abstract
Consensus criteria for traumatic encephalopathy syndrome (TES) specify that at least one core clinical feature of cognitive impairment (CI; e.g., difficulties with memory, executive function) or neurobehavioral dysregulation (ND; e.g., explosiveness, rage, and mood lability) be present and not fully accounted for by other health disorders. Associations between self-reported symptoms that mirror the core clinical features of TES-and how they may be related to concomitant medical conditions-remain unclear. The purpose of this study was to evaluate the association of medical conditions and football exposures with TES clinical features (CI+/-, ND+/-) in 1741 former professional American-style football (ASF) players (age, 57.7 ± 13.9 years; professional seasons, 6.6 ± 3.9 years). Demographics (age, race/ethnicity, current body mass index, age of first football exposure, use of performance-enhancing drugs, position played, and past concussion symptoms), self-reported medical conditions (anxiety, depression, attention-deficit hyperactivity disorder [ADHD], sleep apnea, headache, stroke, hypertension, heart disease, high cholesterol, erectile dysfunction, and low testosterone) were collected. Of 1741 participants, 7.4% were CI+ and/or ND+ (n = 129). Participants who were CI+ or ND+ were more likely to report one or more coexisting medical conditions than participants who did not report CI or ND (odds ratio [OR] = 2.04; 95% confidence interval: 1.25-3.47; p = 0.003). Separate general linear models for each medical condition that adjusted for demographics and football-related factors identified significant associations between ADHD, diabetes, erectile dysfunction, headaches, sleep apnea, anxiety, and low testosterone and CI+ and/or ND+ (ORs = 1.8-6.0). Chi-square automatic interaction detection (CHAID) multi-variable decision tree models that incorporated medical conditions and football exposures accurately differentiated former players meeting either CI or ND clinical criteria from those meeting none (accuracy = 91.2-96.6%). CHAID identified combinations of depression, headache, sleep apnea, ADHD, and upper quartiles of concussion symptom history as most predictive of CI+ and/or ND+ status. CI+ and/or ND+ players were more likely to report medical conditions known to cause cognitive symptoms. Concussion exposure and medical conditions significantly increased the likelihood that a former ASF player would demonstrate cognitive or neurobehavioral dysfunction. Clinicians engaged with this population should consider whether treatable coexisting condition(s) could account for some portion of the clinical picture associated with TES presentation.
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Affiliation(s)
- Rachel Grashow
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Shawn R. Eagle
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Douglas P. Terry
- Vanderbilt Sports Concussion Center, Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | - Aaron L. Baggish
- Harvard Medical School, Boston, Massachusetts, USA
- Cardiovascular Performance Program, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Cardiology, Lausanne University Hospital (CHUV) and Institute for Sport Science, University of Lausanne (ISSUL), Lausanne, Switzerland
| | - Marc G. Weisskopf
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Anthony Kontos
- Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David O. Okonkwo
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ross Zafonte
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, Massachusetts, USA
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA
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Schweitzer N, Son SJ, Aizenstein H, Yang S, Iordanova B, Hong CH, Rho HW, Cho YH, Park B, Kim NR, Choi JW, Cheong JY, Seo SW, An YS, Moon SY, Han SJ, Wu M. Higher HbA1c Is Associated With Greater 2-Year Progression of White Matter Hyperintensities. Diabetes 2024; 73:604-610. [PMID: 38211578 PMCID: PMC10958578 DOI: 10.2337/db23-0303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 01/03/2024] [Indexed: 01/13/2024]
Abstract
White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease. Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study, we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a 2-year follow-up. We found the following. First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (β = 7.7 × 10-4; P = 0.025). Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (P < 0.05, when HbA1c >6.51%), and non-apolipoprotein E (APOE) ε4 carriers had a stronger association between HbA1c and WMHV progression (β = -2.59 × 10-3; P = 0.004). Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (β = 7.17 × 10-4; P < 0.01) compared with periventricular WMHV change and, for frontal (β = 5.00 × 10-4; P < 0.001) and parietal (β = 1.53 × 10-4; P < 0.05) lobes, WMHV change compared with occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater 2-year WMHV progression, especially in non-APOE ε4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease. ARTICLE HIGHLIGHTS
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Affiliation(s)
- Noah Schweitzer
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
| | - Sang Joon Son
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Howard Aizenstein
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Shaolin Yang
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Bistra Iordanova
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
| | - Chang Hyung Hong
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hyun Woong Rho
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Yong Hyuk Cho
- Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Bumhee Park
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea
- Office of Biostatistics, Medical Research Collaborating Centre, Ajou Research Institute for Innovative Medicine, Ajou University Medical Centre, Suwon, Republic of Korea
| | - Na-Rae Kim
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Jin Wook Choi
- Department of Radiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea
- Human Genome Research and Bio-Resource Centre, Ajou University Medical Centre, Suwon, Republic of Korea
| | - Sang Woon Seo
- Department of Neurology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young-Sil An
- Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Republic of Korea
| | - So Young Moon
- Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Seung Jin Han
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Minjie Wu
- Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Reyes Bueno JA, Sánchez-Guijo G, Ráez PD, García-Arnés JA, Garzón-Maldonado FJ, Castro VS, de la Cruz-Cosme C, Alba-Linero C, Gutiérrez-Bedmar M, García-Casares N. Effects of Type 2 Diabetes on the Neuropsychological Profile in Mild Cognitive Impairment. J Alzheimers Dis 2024; 99:887-897. [PMID: 38758998 PMCID: PMC11191518 DOI: 10.3233/jad-230791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/27/2024] [Indexed: 05/19/2024]
Abstract
Background Diabetes is one of the main risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease. Most studies have demonstrated a worse performance in executive function, verbal fluency, and information processing speed in patients with diabetes. Objective To assess the cognitive functioning of persons with type 2 diabetes and amnesic mild cognitive impairment (aMCI-T2DM) compared to persons with aMCI without diabetes and persons without diabetes or aMCI as controls, to understand the role of diabetes in the neuropsychological profile. Methods Cross-sectional study involving a sample of 83 patients, ranging in age from 61 to 85 years and divided into three groups: aMCI-T2DM (27 patients), aMCI (29 patients), Controls (27 individuals). All the participants undertook an exhaustive neuropsychological assessment (auditory-verbal and visual memory, attention, information processing speed, language, executive function, and depression). Results Both groups of aMCI patients performed significantly worse than the controls in all the neuropsychological tests. A significant linear tendency (p trend < 0.05) was found between groups, with the aMCI-T2DM group presenting worse results in global cognition assessed by the Mini-Mental State Examination and Montreal Cognitive Assessment; Rey-Osterrieth Complex Figure Test; Auditory Verbal Learning Test; Trail Making Test A and B, Verbal Fluency Test, and Hamilton Depression Rating Scale. Conclusions aMCI patients with or without diabetes showed worse cognitive function compared to persons without diabetes or aMCI. Additionally, aMCI patients without T2DM presented a different cognitive profile than aMCI patients with T2DM, which tended towards presenting worse cognitive functions such as global cognition, memory, attention, executive function, and language.
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Affiliation(s)
- José A. Reyes Bueno
- Departamento de Neurología, Hospital Universitario Regional de Málaga, Málaga, Spain
| | | | - Pablo Doblas Ráez
- Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - Juan A. García-Arnés
- Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - Francisco J. Garzón-Maldonado
- Departamento de Neurología, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Vicente Serrano Castro
- Departamento de Neurología, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain
| | - Carlos de la Cruz-Cosme
- Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
- Departamento de Neurología, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
| | - Carmen Alba-Linero
- Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Departamento de Oftalmología, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain
| | - Mario Gutiérrez-Bedmar
- Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- CIBERCV Cardiovascular Diseases, Carlos III Health Institute, Madrid, Spain
| | - Natalia García-Casares
- Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain
- Centro de Investigaciones Médico-Sanitarias (CIMES), Spain
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9
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Busby N, Newman-Norlund R, Wilmskoetter J, Johnson L, Rorden C, Gibson M, Roth R, Wilson S, Fridriksson J, Bonilha L. Longitudinal Progression of White Matter Hyperintensity Severity in Chronic Stroke Aphasia. Arch Rehabil Res Clin Transl 2023; 5:100302. [PMID: 38163020 PMCID: PMC10757197 DOI: 10.1016/j.arrct.2023.100302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2024] Open
Abstract
Objective To determine whether longitudinal progression of small vessel disease in chronic stroke survivors is associated with longitudinal worsening of chronic aphasia severity. Design A longitudinal retrospective study. Severity of white matter hyperintensities (WMHs) as a marker for small vessel disease was assessed on fluid-attenuated inversion recovery (FLAIR) scans using the Fazekas scale, with ratings for deep WMHs (DWMHs) and periventricular WMHs (PVHs). Setting University research laboratories. Participants This study includes data from 49 chronic stroke survivors with aphasia (N=49; 15 women, 34 men, age range=32-81 years, >6 months post-stroke, stroke type: [46 ischemic, 3 hemorrhagic], community dwelling). All participants completed the Western Aphasia Battery-Revised (WAB) and had FLAIR scans at 2 timepoints (average years between timepoints: 1.87 years, SD=3.21 years). Interventions Not applicable. Main Outcome Measures Change in white matter hyperintensity severity (calculated using the Fazekas scale) and change in aphasia severity (difference in Western Aphasia Battery scores) were calculated between timepoints. Separate stepwise regression models were used to identify predictors of WMH severity change, with lesion volume, age, time between timepoints, body mass index (BMI), and presence of diabetes as independent variables. Additional stepwise regression models investigated predictors of change in aphasia severity, with PVH change, DWMH change, lesion volume, time between timepoints, and age as independent predictors. Results 22.5% of participants (11/49) had increased WMH severity. Increased BMI was associated with increases in PVH severity (P=.007), whereas the presence of diabetes was associated with increased DWMH severity (P=.002). Twenty-five percent of participants had increased aphasia severity which was significantly associated with increased severity of PVH (P<.001, 16.8% variance explained). Conclusion Increased small vessel disease burden is associated with contributing to chronic changes in aphasia severity. These findings support the idea that good cardiovascular risk factor control may play an important role in the prevention of long-term worsening of aphasic symptoms.
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Affiliation(s)
- Natalie Busby
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC
| | | | - Janina Wilmskoetter
- Department of Neurology, Medical University of South Carolina, Charleston, SC
| | - Lisa Johnson
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC
| | - Chris Rorden
- Department of Psychology, University of South Carolina, Columbia, SC
| | - Makayla Gibson
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC
| | - Rebecca Roth
- Department of Neurology, Emory University, Atlanta, GA
| | - Sarah Wilson
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC
| | - Julius Fridriksson
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC
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10
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Yoshida T, Mori T, Shimizu H, Tachibana A, Yoshino Y, Ochi S, Yamazaki K, Ozaki Y, Kawabe K, Horiuchi F, Komori K, Iga JI, Ueno SI. Analysis of factors related to cognitive impairment in a community-based, complete enumeration survey in Japan: the Nakayama study. Psychogeriatrics 2023; 23:876-884. [PMID: 37483119 DOI: 10.1111/psyg.13012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 07/05/2023] [Accepted: 07/07/2023] [Indexed: 07/25/2023]
Abstract
BACKGROUND The number of patients with cognitive disorders is rapidly increasing in the world, becoming not only a medical problem, but also a social problem. There have been many reports that various factors are associated with cognitive dysfunction, but the factors have not yet been fully identified. This was a community-based complete enumeration study which aimed to identify risk and protective factors for dementia. METHODS The first phase included all residents aged 65 years or older in a town in Japan. They completed many examinations, such as living conditions questionnaires, physical examination, Mini-Mental State Examination, and brain magnetic resonance imaging. The participants with suspected cognitive impairment underwent additional examinations for detailed evaluation in the second phase. Statistical analysis was performed to identify risk and protective factors for dementia after all participants were diagnosed. RESULTS There were 927 participants in the baseline evaluation; 611 (65.9%) were healthy, 165 (17.8%) had mild cognitive impairment (MCI), and 151 (16.3%) had dementia. The age-standardised prevalence of dementia was 9.5%. Statistical analyses for amnestic MCI and Alzheimer's disease showed that risk factors for cognitive decline were diabetes mellitus, low activities of daily living, and living alone, and that protective factors were history of exercise and drinking habit. CONCLUSION The present findings suggest that several lifestyle-related diseases and factors are associated with cognitive decline. These results support similar findings from previous studies and will be helpful for preventing dementia in the future.
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Affiliation(s)
- Taku Yoshida
- Department of Psychiatry, Zaidan Niihama Hospital, Niihama, Japan
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Takaaki Mori
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
- Department of Psychiatry, Heisei Hospital, Ozu, Japan
| | - Hideaki Shimizu
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
- Department of Psychiatry, Heisei Hospital, Ozu, Japan
| | - Ayumi Tachibana
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
- Department of Psychiatry, Matsukaze Hospital, Shikokuchuou, Japan
| | - Yuta Yoshino
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Shinichiro Ochi
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Kiyohiro Yamazaki
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Yuki Ozaki
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Kentaro Kawabe
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Fumie Horiuchi
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Kenjiro Komori
- Department of Psychiatry, Zaidan Niihama Hospital, Niihama, Japan
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
- Office of Psychology, Department of Psychiatry, Juzen-Yurinoki Hospital, Niihama, Japan
| | - Jun-Ichi Iga
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
| | - Shu-Ichi Ueno
- Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Toon, Japan
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11
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Franciotti R, Sensi SL. Editorial: Collection on renal disease, diabetes and cognitive performance. Front Hum Neurosci 2023; 17:1240691. [PMID: 37694173 PMCID: PMC10486016 DOI: 10.3389/fnhum.2023.1240691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 08/18/2023] [Indexed: 09/12/2023] Open
Affiliation(s)
- Raffaella Franciotti
- Department of Neuroscience, Imaging and Clinical Science, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy
| | - Stefano Luca Sensi
- Department of Neuroscience, Imaging and Clinical Science, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy
- Center for Advanced Studies and Technology (CAST), Institute for Advanced Biomedical Technologies, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy
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12
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Wang X, Hui X, Wang X, Huang B, Gan X, Liu X, Shen Z, Sun Y, Li L. Utilization of clinical and radiological parameters to predict cognitive prognosis in patients with mild-to-moderate traumatic brain injury. Front Neurosci 2023; 17:1222541. [PMID: 37575301 PMCID: PMC10412890 DOI: 10.3389/fnins.2023.1222541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 07/03/2023] [Indexed: 08/15/2023] Open
Abstract
Background Cognitive impairment is a common sequela following traumatic brain injury (TBI). This study aimed to identify risk factors for cognitive impairment after 3 and 12 months of TBI and to create nomograms to predict them. Methods A total of 305 mild-to-moderate TBI patients admitted to the First Affiliated Hospital with Nanjing Medical University from January 2018 to January 2022 were retrospectively recruited. Risk factors for cognitive impairment after 3 and 12 months of TBI were identified by univariable and multivariable logistic regression analyses. Based on these factors, we created two nomograms to predict cognitive impairment after 3 and 12 months of TBI, the discrimination and calibration of which were validated by plotting the receiver operating characteristic (ROC) curve and calibration curve, respectively. Results Cognitive impairment was detected in 125/305 and 52/305 mild-to-moderate TBI patients after 3 and 12 months of injury, respectively. Age, the Glasgow Coma Scale (GCS) score, >12 years of education, hyperlipidemia, temporal lobe contusion, traumatic subarachnoid hemorrhage (tSAH), very early rehabilitation (VER), and intensive care unit (ICU) admission were independent risk factors for cognitive impairment after 3 months of mild-to-moderate TBI. Meanwhile, age, GCS score, diabetes mellitus, tSAH, and surgical treatment were independent risk factors for cognitive impairment after 12 months of mild-to-moderate TBI. Two nomograms were created based on the risk factors identified using logistic regression analyses. The areas under the curve (AUCs) of the two nomograms to predict cognitive impairment after 3 and 12 months of mild-to-moderate TBI were 0.852 (95% CI [0.810, 0.895]) and 0.817 (95% CI [0.762, 0.873]), respectively. Conclusion Two nomograms are created to predict cognitive impairment after 3 and 12 months of TBI. Age, GCS score, >12 years of education, hyperlipidemia, temporal lobe contusion, tSAH, VER, and ICU admission are independent risk factors for cognitive impairment after 3 months of TBI; meanwhile, age, the GCS scores, diabetes mellitus, tSAH, and surgical treatment are independent risk factors of cognitive impairment after 12 months of TBI. Two nomograms, based on both groups of factors, respectively, show strong discriminative abilities.
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Affiliation(s)
- Xi Wang
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaobo Hui
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Neurosurgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China
| | - Xiangyu Wang
- Department of Rehabilitation Medicine, The Affiliated Lianyungang Oriental Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, China
| | - Baosheng Huang
- Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaokui Gan
- Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China
| | - Xingdong Liu
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhiyan Shen
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yi Sun
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lixin Li
- Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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13
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Roth R, Busby N, Wilmskoetter J, Schwen Blackett D, Gleichgerrcht E, Johnson L, Rorden C, Newman-Norlund R, Hillis AE, den Ouden DB, Fridriksson J, Bonilha L. Diabetes, brain health, and treatment gains in post-stroke aphasia. Cereb Cortex 2023; 33:8557-8564. [PMID: 37139636 PMCID: PMC10321080 DOI: 10.1093/cercor/bhad140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 03/31/2023] [Accepted: 04/01/2023] [Indexed: 05/05/2023] Open
Abstract
In post-stroke aphasia, language improvements following speech therapy are variable and can only be partially explained by the lesion. Brain tissue integrity beyond the lesion (brain health) may influence language recovery and can be impacted by cardiovascular risk factors, notably diabetes. We examined the impact of diabetes on structural network integrity and language recovery. Seventy-eight participants with chronic post-stroke aphasia underwent six weeks of semantic and phonological language therapy. To quantify structural network integrity, we evaluated the ratio of long-to-short-range white matter fibers within each participant's whole brain connectome, as long-range fibers are more susceptible to vascular injury and have been linked to high level cognitive processing. We found that diabetes moderated the relationship between structural network integrity and naming improvement at 1 month post treatment. For participants without diabetes (n = 59), there was a positive relationship between structural network integrity and naming improvement (t = 2.19, p = 0.032). Among individuals with diabetes (n = 19), there were fewer treatment gains and virtually no association between structural network integrity and naming improvement. Our results indicate that structural network integrity is associated with treatment gains in aphasia for those without diabetes. These results highlight the importance of post-stroke structural white matter architectural integrity in aphasia recovery.
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Affiliation(s)
- Rebecca Roth
- Department of Neurology, Emory University, Atlanta, GA 30322, USA
| | - Natalie Busby
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC 29208, USA
| | - Janina Wilmskoetter
- Department of Rehabilitation Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Deena Schwen Blackett
- Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Ezequiel Gleichgerrcht
- Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Lisa Johnson
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC 29208, USA
| | - Chris Rorden
- Department of Psychology, University of South Carolina, Columbia, SC 29208, USA
| | | | - Argye E Hillis
- Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD 21218 USA
| | - Dirk B den Ouden
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC 29208, USA
| | - Julius Fridriksson
- Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC 29208, USA
| | - Leonardo Bonilha
- Department of Neurology, Emory University, Atlanta, GA 30322, USA
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14
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Zhang X, Guo F, Cao D, Yan Y, Zhang N, Zhang K, Li X, Kumar P, Zhang X. Neuroprotective Effect of Ponicidin Alleviating the Diabetic Cognitive Impairment: Regulation of Gut Microbiota. Appl Biochem Biotechnol 2023; 195:735-752. [PMID: 36155887 DOI: 10.1007/s12010-022-04113-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2022] [Indexed: 01/24/2023]
Abstract
Cognitive impairment is a major complication of diabetes mellitus, which is caused by constitutive hyperglycaemia. Ponicidin is a diterpenoid isolated from a Chinese traditional herb (Rabdosia rubescens) and demonstrates the various pharmacological effects. The goal of this study was to scrutinise the neuroprotective effect of ponicidin against diabetic nephropathy (DN) induced by streptozotocin (STZ). Intraperitoneal administration of STZ (55 mg/kg) was used for the induction of diabetes and rats were received oral administration of ponicidin (5, 10 and 15 mg/kg) until 28 days. The body weight, food intake, water intake and blood glucose level were assessed at regular time interval. Plasma insulin level, antioxidant, inflammatory cytokines, apoptosis marker and faecal gut microbiota compositions were estimated. DN-induced group rats revealed the augmented glucose level, water intake, food intake and reduced body weight. Ponicidin significantly (P < 0.001) repressed the glucose level and water food intake and improved the body weight and plasma insulin. Ponicidin significantly (P < 0.001) repressed the malonaldehyde (MDA) level and boosted the level of glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) in the brain and serum level. Ponicidin significantly (P < 0.001) repressed the level of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and enhanced the level of interleukin-4 (IL-4), interleukin-10 (IL-10) in the brain and serum level. DN group rats exhibited the enhanced relative abundance of Firmicutes, along with enhancing the Firmicutes/Bacteroidetes ratio and repressing the Bacteroidetes relative abundance. Ponicidin effectually restored the relative abundance of Allobaculum, Lactobacillus and Ruminococcus genera. Our findings clearly demonstrated that ponicidin has a neuroprotective effect against diabetic cognitive impairment through modulating the gut microbiome.
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Affiliation(s)
- Xiaojuan Zhang
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.,Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Feng Guo
- People's Hospital of Lvliang, Shanxi, 033000, China
| | - Dujuan Cao
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.,Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yinan Yan
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.,Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ning Zhang
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.,Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Kaili Zhang
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.,Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xinyi Li
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China. .,Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | | | - Xiaojuan Zhang
- Department of Neurology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.,Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
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15
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Brenner EK, Weigand AJ, Edwards L, Thomas KR, Edmonds EC, Bondi MW, Bangen KJ. Brain Derived Neurotrophic Factor Interacts with White Matter Hyperintensities to Influence Processing Speed and Hippocampal Volume in Older Adults. J Alzheimers Dis 2023; 93:141-149. [PMID: 36970903 PMCID: PMC10200154 DOI: 10.3233/jad-221178] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
BACKGROUND Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in regulating synaptic activity and plasticity. OBJECTIVE Given that type-2 diabetes (T2DM) increases the risk of cognitive decline, and studies have suggested lower BDNF levels may be a risk factor of diabetic neurovascular complications, we sought to investigate total white matter hyperintensities (WMH) as a moderator of the effect of BDNF on hippocampal volume and cognition. METHODS Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative (N = 454 including 49 with T2DM and 405 without diabetes) underwent neuropsychological evaluation, magnetic resonance imaging to quantify hippocampal and WMH volumes, and blood draw to assess BDNF. RESULTS Adjusting for age, sex, and APOE ɛ4 carrier status, there was a significant interaction between total WMH and BDNF on bilateral hippocampal volume in the non-T2DM group (t = 2.63, p = 0.009). Examination of main effect models with a dichotomous high/low BNDF group revealed a significant main effect for low BDNF (t = -4.98, p < 0.001), such that as WMH increased, bilateral hippocampal volume decreased. There was also a significant interaction between total WMH and BDNF on processing speed in the non-T2DM group (t = 2.91, p = 0.004). There was a significant main effect for low BDNF (t = -3.55, p < 0.001) such that as WMH increased, processing speed decreased. The interactions were not significant in the T2DM group. CONCLUSION These results further elucidate the protective role that BDNF plays on cognition, as well as the cognitive effects of WMH.
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Affiliation(s)
- Einat K. Brenner
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Alexandra J. Weigand
- San Diego State University/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
| | - Lauren Edwards
- San Diego State University/UC San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
| | - Kelsey R. Thomas
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
| | | | - Mark W. Bondi
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
| | - Katherine J. Bangen
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
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16
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Agunloye OM, Oboh G. Fermented seeds of Pentaclethra macrophylla mitigate against memory deficit and restored altered enzymatic activity in the brain of streptozotocin-diabetic rats. Metab Brain Dis 2022; 38:973-981. [PMID: 36585563 DOI: 10.1007/s11011-022-01141-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 12/03/2022] [Indexed: 01/01/2023]
Abstract
Memory deficit has been reported as one of the complications of diabetes. Fermented seeds of Pentaclethra Macrophylla (P. macrophylla) have been used in folklore for the management of metabolic diseases. The research aims to evaluate the impact of diets with the inclusion of the fermented seed of P. macrophylla on memory deficit in diabetic rats and its underlying mechanisms. Before the induction, the rats were subjected to training sessions. Thereafter, streptozotocin (50 mg/kg body weight) was administered to the trained rats via intraperitoneal (i.p). 72 hours after, the rats blood glucose level was checked, rats with blood glucose level greater than 250 mg/dl were selected for the memory index evaluation study. The induced rats were randomly distributed into groups: Normal rats (group 1), untreated diabetic rat (Group 2), acarbose treated diabetic rats (group 3); diabetic rats placed on diet supplemented with fermented seed of P. macrophylla (10 & 20% inclusion) were allotted to group 4 & 5. Then, evaluation of memory retention capacity was performed on the day 14 of the experiment. Thereafter, experimental rats were sacrificed, tissue of interest (brain) was excised, homogenized and homogenates were used for biochemical analysis. The cholinergic, angiotensin-1-converting enzyme (ACE), arginase activity and biomarkers for oxidative stress were significantly altered in untreated diabetic rats when compared with non-diabetes rats. Also, the memory capacity of the diabetic rats was significantly reduced when compared with the non-diabetes rats. Meanwhile, diabetic rats placed on diet with fermented seeds of P. macrophylla (10 & 20% inclusion) exhibited significantly higher memory capacity, lower activity of cholinergic, ACE, arginase activity in relation to untreated diabetic rats while the antioxidant status of the brain was enhanced. Nevertheless, fermented seeds of P. macrophylla ameliorated memory deficit in STZ induced diabetes rats. This gave credence to P. macrophylla nutraceutical potential as claimed in folk medicine.
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Affiliation(s)
- Odunayo Michael Agunloye
- Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, Akure, Nigeria.
| | - Ganiyu Oboh
- Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, Akure, Nigeria
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17
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Gao H, Zhou Y, Jin PS, Wu DG, Wang YN, Zhao X, Zhao B. Molecular alteration of the proteasome contributes to AD-like pathology in the brain of HFD-STZ diabetic rats. Metab Brain Dis 2022; 38:1013-1024. [PMID: 36580191 DOI: 10.1007/s11011-022-01151-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 12/21/2022] [Indexed: 12/30/2022]
Abstract
Diabetes-related cognitive impairment has been shown in diverse epidemiological investigations and lab-based studies, although the underlying pathological mechanisms remain unclear. Unbalanced protein homeostasis may contribute to cognitive decline by inducing abnormal protein aggregation in the diabetic brain. This study aimed to determine possible changes in the proteasome, which is an important pathway involved in abnormal protein degradation. To this end, we examined potential alterations of proteasomal subunits and hydrolytic activity in the brain of diabetic rats fed with high-fat diet combined with small doses of streptozotocin (STZ). Furthermore, lactacystin were used to inhibit proteasomal activity in vivo and typical Alzheimer's disease (AD)-like pathologies were detected, including amyloid-beta, tau phosphorylation, and oxidative protein changes. Our results showed that proteasomal activity increased in the brains of diabetic rats compared to age-matched control rats. After proteasome inhibition, the levels of tau phosphorylation and protein oxidative modification significantly increased; however, no changes were detected in the pathway involved in amyloid production. These results indicated that changes in protein homeostasis balance in diabetes play a role in some typical AD-like changes, especially in oxidative protein degradation, providing evidence that prevention of diabetes-induced protein imbalance may be a potential therapeutic target.
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Affiliation(s)
- Han Gao
- School of Basic Medicine Sciences, Dali University, 6Th Xue-Ren Road, Dali, 671000, Yunnan Province, People's Republic of China
| | - Ye Zhou
- School of Basic Medicine Sciences, Dali University, 6Th Xue-Ren Road, Dali, 671000, Yunnan Province, People's Republic of China
| | - Peng-Shuai Jin
- School of Basic Medicine Sciences, Dali University, 6Th Xue-Ren Road, Dali, 671000, Yunnan Province, People's Republic of China
- Zhalantun Vocational College, 20Th Zhongyang Road, Hulunbuir, NeiMonggol Autonomous Region, People's Republic of China
| | - Dong-Gui Wu
- School of Basic Medicine Sciences, Dali University, 6Th Xue-Ren Road, Dali, 671000, Yunnan Province, People's Republic of China
- Zhuhai City People's Hospital, Zhuhai, Guangdong Province, People's Republic of China
| | - Yu-Na Wang
- School of Basic Medicine Sciences, Dali University, 6Th Xue-Ren Road, Dali, 671000, Yunnan Province, People's Republic of China
| | - Xi Zhao
- School of Basic Medicine Sciences, Dali University, 6Th Xue-Ren Road, Dali, 671000, Yunnan Province, People's Republic of China
| | - Bei Zhao
- School of Basic Medicine Sciences, Dali University, 6Th Xue-Ren Road, Dali, 671000, Yunnan Province, People's Republic of China.
- Li Yunqing Expert Workstation of Yunnan Province (No.202005AF150014), Dali University, 6Th Xue-Ren Road, Dali, Yunnan Province, People's Republic of China.
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18
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Snyder LL, Foland-Ross LC, Cato A, Reiss AL, Shah C, Hossain J, Elmufti H, Nelly Mauras. Impact of dysglycemia and obesity on the brain in adolescents with and without type 2 diabetes: A pilot study. Pediatr Diabetes 2022; 23:1674-1686. [PMID: 36131363 DOI: 10.1111/pedi.13420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/04/2022] [Accepted: 09/17/2022] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE Both diabetes and obesity can affect the brain, yet their impact is not well characterized in children with type 2 (T2) diabetes and obesity. This pilot study aims to explore differences in brain function and cognition in adolescents with T2 diabetes and obesity and nondiabetic controls with obesity and lean controls. RESEARCH DESIGN AND METHODS Participants were 12-17 years old (5 T2 diabetes with obesity [mean HgbA1C 10.9%], 6 nondiabetic controls with obesity and 10 lean controls). Functional MRI (FMRI) during hyperglycemic/euglycemic clamps was performed in the T2 diabetes group. RESULTS When children with obesity, with and without diabetes, were grouped (mean BMI 98.8%), cognitive scores were lower than lean controls (BMI 58.4%) on verbal, full scale, and performance IQ, visual-spatial and executive function tests. Lower scores correlated with adiposity and insulin resistance but not HgbA1C. No significant brain activation differences during task based and resting state FMRI were noted between children with obesity (with or without diabetes) and lean controls, but a notable effect size for the visual-spatial working memory task and resting state was observed. CONCLUSIONS In conclusion, our pilot study suggests that obesity, insulin resistance, and dysglycemia may contribute to relatively poorer cognitive function in adolescents with T2 diabetes and obesity. Further studies with larger sample size are needed to assess if cognitive decline in children with obesity, with and without T2 diabetes, can be prevented or reversed.
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Affiliation(s)
- Lydia L Snyder
- Nemours Children's Health, Pediatric Endocrinology, Jacksonville, Florida, USA
| | - Lara C Foland-Ross
- Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, California, USA
| | - Allison Cato
- Nemours Children's Health, Pediatric Neuropsychology, Jacksonville, Florida, USA
| | - Allan L Reiss
- Center for Interdisciplinary Brain Sciences Research, Stanford University, Stanford, California, USA
| | - Chetan Shah
- Nemours Children's Health, Pediatric Neuroradiology, Jacksonville, Florida, USA
| | - Jobayer Hossain
- Nemours Children's Health, Nemours Biomedical Research, Biostatistics Core, Wilmington, Delaware, USA
| | - Hussein Elmufti
- Nemours Children's Health, Pediatric Endocrinology, Jacksonville, Florida, USA
| | - Nelly Mauras
- Nemours Children's Health, Pediatric Endocrinology, Jacksonville, Florida, USA
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19
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Kang S, Chen Y, Wu J, Liang Y, Rao Y, Yue X, Lyu W, Li Y, Tan X, Huang H, Qiu S. Altered cortical thickness, degree centrality, and functional connectivity in middle-age type 2 diabetes mellitus. Front Neurol 2022; 13:939318. [PMID: 36408505 PMCID: PMC9672081 DOI: 10.3389/fneur.2022.939318] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 10/12/2022] [Indexed: 05/01/2024] Open
Abstract
PURPOSE This study aimed to investigate the changes in brain structure and function in middle-aged patients with type 2 diabetes mellitus (T2DM) using morphometry and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). METHODS A total of 44 middle-aged patients with T2DM and 45 matched healthy controls (HCs) were recruited. Surface-based morphometry (SBM) was used to evaluate the changes in brain morphology. Degree centrality (DC) and functional connectivity (FC) were used to evaluate the changes in brain function. RESULTS Compared with HCs, middle-aged patients with T2DM exhibited cortical thickness reductions in the left pars opercularis, left transverse temporal, and right superior temporal gyri. Decreased DC values were observed in the cuneus and precuneus in T2DM. Hub-based FC analysis of these regions revealed lower connectivity in the bilateral hippocampus and parahippocampal gyrus, left precuneus, as well as left frontal sup. CONCLUSION Cortical thickness, degree centrality, as well as functional connectivity were found to have significant changes in middle-aged patients with T2DM. Our observations provide potential evidence from neuroimaging for analysis to examine diabetes-related brain damage.
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Affiliation(s)
- Shangyu Kang
- The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuna Chen
- Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jinjian Wu
- The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yi Liang
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yawen Rao
- The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaomei Yue
- The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wenjiao Lyu
- The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yifan Li
- The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xin Tan
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Haoming Huang
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shijun Qiu
- Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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20
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Zhang T, Shaw M, Cherbuin N. Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis. Diabetes Metab J 2022; 46:781-802. [PMID: 35255549 PMCID: PMC9532183 DOI: 10.4093/dmj.2021.0189] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 12/11/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM. METHODS PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression. RESULTS A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration. CONCLUSION T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.
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Affiliation(s)
- Tianqi Zhang
- Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, Australia
| | - Marnie Shaw
- Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, Australia
| | - Nicolas Cherbuin
- Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, Australia
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21
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van der Kooij MA, Rojas-Charry L, Givehchi M, Wolf C, Bueno D, Arndt S, Tenzer S, Mattioni L, Treccani G, Hasch A, Schmeisser MJ, Vianello C, Giacomello M, Methner A. Chronic social stress disrupts the intracellular redistribution of brain hexokinase 3 induced by shifts in peripheral glucose levels. J Mol Med (Berl) 2022; 100:1441-1453. [PMID: 35943566 PMCID: PMC9470722 DOI: 10.1007/s00109-022-02235-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 06/06/2022] [Accepted: 07/04/2022] [Indexed: 11/26/2022]
Abstract
Abstract
Chronic stress has the potential to impair health and may increase the vulnerability for psychiatric disorders. Emerging evidence suggests that specific neurometabolic dysfunctions play a role herein. In mice, chronic social defeat (CSD) stress reduces cerebral glucose uptake despite hyperglycemia. We hypothesized that this metabolic decoupling would be reflected by changes in contact sites between mitochondria and the endoplasmic reticulum, important intracellular nutrient sensors, and signaling hubs. We thus analyzed the proteome of their biochemical counterparts, mitochondria-associated membranes (MAMs) from whole brain tissue obtained from CSD and control mice. This revealed a lack of the glucose-metabolizing enzyme hexokinase 3 (HK3) in MAMs from CSD mice. In controls, HK3 protein abundance in MAMs and also in striatal synaptosomes correlated positively with peripheral blood glucose levels, but this connection was lost in CSD. We conclude that the ability of HK3 to traffic to sites of need, such as MAMs or synapses, is abolished upon CSD and surmise that this contributes to a cellular dysfunction instigated by chronic stress.
Key messages
Chronic social defeat (CSD) alters brain glucose metabolism CSD depletes hexokinase 3 (HK3) from mitochondria-associated membranes (MAMs) CSD results in loss of positive correlation between blood glucose and HK3 in MAMs and synaptosomes
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Affiliation(s)
| | - Liliana Rojas-Charry
- Institute for Molecular Medicine, Johannes Gutenberg University Mainz, Mainz, 55131, Germany.,Institute of Anatomy, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Maryam Givehchi
- Leibniz Institute for Resilience Research (LIR), Mainz, 55122, Germany
| | - Christina Wolf
- Institute for Molecular Medicine, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Diones Bueno
- Institute for Molecular Medicine, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Sabine Arndt
- Institute for Immunology, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Stefan Tenzer
- Institute for Immunology, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Lorenzo Mattioni
- Institute of Anatomy, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Giulia Treccani
- Institute of Anatomy, Johannes Gutenberg University Mainz, Mainz, 55131, Germany.,Department of Psychiatry and Psychotherapy, Translational Psychiatry, University Medical Center, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Annika Hasch
- Leibniz Institute for Resilience Research (LIR), Mainz, 55122, Germany
| | - Michael J Schmeisser
- Institute of Anatomy, Johannes Gutenberg University Mainz, Mainz, 55131, Germany
| | - Caterina Vianello
- Institute for Molecular Medicine, Johannes Gutenberg University Mainz, Mainz, 55131, Germany.,Department of Biology, University of Padua, Padua, 35121, Italy
| | | | - Axel Methner
- Institute for Molecular Medicine, Johannes Gutenberg University Mainz, Mainz, 55131, Germany.
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22
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Park KY, Nam GE, Han K, Hwang HS. Body weight variability and the risk of dementia in patients with type 2 diabetes mellitus: A nationwide cohort study in Korea. Diabetes Res Clin Pract 2022; 190:110015. [PMID: 35907508 DOI: 10.1016/j.diabres.2022.110015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 07/08/2022] [Accepted: 07/18/2022] [Indexed: 11/03/2022]
Abstract
AIMS This study aimed to examine the association between body weight variability and dementia risk using a large-scale cohort data of Korean patients with type 2 diabetes mellitus (T2DM). METHODS A population-based cohort of 1,206,764 individuals with T2DM aged ≥ 40 years who underwent ≥ 3 Korean national health screenings were followed up until the end of 2019. Body weight variability was assessed using variability independent of the mean (VIM). A multivariate Cox proportional hazard regression was performed with calculating hazard ratios (HRs) with 95 % confidence intervals (CIs) of dementia incidence. RESULTS During a median follow-up of 7.9 years, 162,615 (13.4 %) individuals developed dementia. Individuals with greater body weight variability tended to be associated with higher risk of all types of dementia (P for trend < 0.001). Individuals in the highest quartile of VIM showed 26 % (HR: 1.26, 95 % CI: 1.24-1.28), 33 % (HR: 1.33, 95 % CI: 1.30-1.36) and 28 % (HR: 1.28, 95 % CI: 1.23-1.33) higher risk for all-cause dementia, Alzheimer's disease, and vascular dementia, compared with those in the lowest quartile. These associations persisted in all body mass index categories (P for trend < 0.001). CONCLUSIONS Maintaining an appropriate body weight may help mitigate dementia risk in patients with T2DM.
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Affiliation(s)
- Kye-Yeung Park
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea.
| | - Ga Eun Nam
- Department of Family Medicine, Korea University College of Medicine, Seoul, South Korea.
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea.
| | - Hwan-Sik Hwang
- Department of Family Medicine, Hanyang University College of Medicine, Seoul, South Korea.
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23
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Jacobson AM, Braffett BH, Erus G, Ryan CM, Biessels GJ, Luchsinger JA, Bebu I, Gubitosi-Klug RA, Desiderio L, Lorenzi GM, Trapani VR, Lachin JM, Bryan RN, Habes M, Nasrallah IM. Brain Structure Among Middle-aged and Older Adults With Long-standing Type 1 Diabetes in the DCCT/EDIC Study. Diabetes Care 2022; 45:1779-1787. [PMID: 35699949 PMCID: PMC9346989 DOI: 10.2337/dc21-2438] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 04/17/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Individuals with type 1 diabetes mellitus (T1DM) are living to ages when neuropathological changes are increasingly evident. We hypothesized that middle-aged and older adults with long-standing T1DM will show abnormal brain structure in comparison with control subjects without diabetes. RESEARCH DESIGN AND METHODS MRI was used to compare brain structure among 416 T1DM participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study with that of 99 demographically similar control subjects without diabetes at 26 U.S. and Canadian sites. Assessments included total brain (TBV) (primary outcome), gray matter (GMV), white matter (WMV), ventricle, and white matter hyperintensity (WMH) volumes and total white matter mean fractional anisotropy (FA). Biomedical assessments included HbA1c and lipid levels, blood pressure, and cognitive assessments of memory and psychomotor and mental efficiency (PME). Among EDIC participants, HbA1c, severe hypoglycemia history, and vascular complications were measured longitudinally. RESULTS Mean age of EDIC participants and control subjects was 60 years. T1DM participants showed significantly smaller TBV (least squares mean ± SE 1,206 ± 1.7 vs. 1,229 ± 3.5 cm3, P < 0.0001), GMV, and WMV and greater ventricle and WMH volumes but no differences in total white matter mean FA versus control subjects. Structural MRI measures in T1DM were equivalent to those of control subjects who were 4-9 years older. Lower PME scores were associated with altered brain structure on all MRI measures in T1DM participants. CONCLUSIONS Middle-aged and older adults with T1DM showed brain volume loss and increased vascular injury in comparison with control subjects without diabetes, equivalent to 4-9 years of brain aging.
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Affiliation(s)
- Alan M. Jacobson
- NYU Long Island School of Medicine, NYU Langone Hospital–Long Island, Mineola
| | | | - Guray Erus
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
| | | | - Geert J. Biessels
- Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Netherlands
| | | | - Ionut Bebu
- The Biostatistics Center, The George Washington University, Rockville, MD
| | - Rose A. Gubitosi-Klug
- Case Western Reserve University School of Medicine, Rainbow Babies & Children’s Hospital, Cleveland, OH
| | - Lisa Desiderio
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
| | | | | | - John M. Lachin
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
| | | | - Mohamad Habes
- Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX
| | - Ilya M. Nasrallah
- Department of Radiology, University of Pennsylvania, Philadelphia, PA
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24
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Luo A, Xie Z, Wang Y, Wang X, Li S, Yan J, Zhan G, Zhou Z, Zhao Y, Li S. Type 2 diabetes mellitus-associated cognitive dysfunction: Advances in potential mechanisms and therapies. Neurosci Biobehav Rev 2022; 137:104642. [PMID: 35367221 DOI: 10.1016/j.neubiorev.2022.104642] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 03/24/2022] [Accepted: 03/27/2022] [Indexed: 12/22/2022]
Abstract
Type 2 diabetes (T2D) and its target organ injuries cause distressing impacts on personal health and put an enormous burden on the healthcare system, and increasing attention has been paid to T2D-associated cognitive dysfunction (TDACD). TDACD is characterized by cognitive dysfunction, delayed executive ability, and impeded information-processing speed. Brain imaging data suggest that extensive brain regions are affected in patients with T2D. Based on current findings, a wide spectrum of non-specific neurodegenerative mechanisms that partially overlap with the mechanisms of neurodegenerative diseases is hypothesized to be associated with TDACD. However, it remains unclear whether TDACD is a consequence of T2D or a complication that co-occurs with T2D. Theoretically, anti-diabetes methods are promising neuromodulatory approaches to reduce brain injury in patients with T2D. In this review, we summarize potential mechanisms underlying TDACD and promising neurotropic effects of anti-diabetes methods and some neuroprotective natural compounds. Constructing screening or diagnostic tools and developing targeted treatment and preventive strategies would be expected to reduce the burden of TDACD.
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Affiliation(s)
- Ailin Luo
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Zheng Xie
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Yue Wang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Xuan Wang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Shan Li
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Jing Yan
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Gaofeng Zhan
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Zhiqiang Zhou
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Yilin Zhao
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
| | - Shiyong Li
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
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25
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Öksüz Ö, Günver MG, Arıkan MK. Quantitative Electroencephalography Findings in Patients With Diabetes Mellitus. Clin EEG Neurosci 2022; 53:248-255. [PMID: 33729035 DOI: 10.1177/1550059421997657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Objective. Diabetes mellitus (DM) causes structural central nervous system (CNS) impairment, and this situation can be detected by quantitative electroencephalography (QEEG) findings before cognitive impairment is clinically observed. The main aim of this study is to uncover the effect of DM on brain function. Since QEEG reflects the CNS functioning, particularly in cognitive aspects, we expected electrophysiological clues to be found for prevention and follow-up in DM-related cognitive decline. Since a majority of the psychiatric population have cognitive dysfunction, we have given particular attention to those people. It was stated that a decrease was observed in the posterior cortical alpha power due to the hippocampal atrophy by several previous studies and we hypothesize that decreased alpha power will be observed also in DM. Methods. This study included 2094 psychiatric patients, 207 of whom were diagnosed with DM and 1887 of whom were not diagnosed with DM, and QEEG recordings were performed. Eyes-closed electroencephalography data were segmented into consecutive 2 s epochs. Fourier analysis was performed by averaging across 2 s epochs without artifacts. The absolute alpha power in the occipital regions (O1 and O2) of patients with and without DM was compared. Results. In the DM group, a decrease in the absolute alpha, alpha 1, and alpha 2 power in O1 and O2 was observed in comparison with the control group. It was determined that the type of psychiatric diagnosis did not affect QEEG findings. Conclusion. The decrease in absolute alpha power observed in patients diagnosed with DM may be related to the CNS impairment in DM. QEEG findings in DM can be useful while monitoring the CNS impairment, diagnosing DM-related dementia, in the follow-up of the cognitive process, constructing the protocols for electrophysiological interventions like neurofeedback and transcranial magnetic stimulation and monitoring the response to treatment.
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Affiliation(s)
- Özden Öksüz
- Department of Neuroscience, 52998Yeditepe University, İstanbul, Turkey
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26
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Redel JM, DiFrancesco M, Lee GR, Ziv A, Dolan LM, Brady CC, Shah AS. Cerebral blood flow is lower in youth with type 2 diabetes compared to obese controls: A pilot study. Pediatr Diabetes 2022; 23:291-300. [PMID: 35001473 DOI: 10.1111/pedi.13313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 12/15/2021] [Accepted: 01/03/2022] [Indexed: 11/30/2022] Open
Abstract
AIM The cerebral vasculature may be susceptible to the adverse effects of type 2 diabetes. In this pilot study, we compared cerebral blood flow (CBF) in youth with type 2 diabetes to obese, euglycemic controls, and explored the association between CBF and a non-invasive measure of atherosclerosis, carotid intima-medial thickness (IMT). METHODS Global and regional CBF were compared between youth with type 2 diabetes (mean age 16.7 ± 2.0 years, n = 20) and age, race, and sex similar obese youth without diabetes (17.4 ± 1.9 years, n = 19) using arterial spin labeling magnetic resonance imaging. Mean CBF values were compared between groups. Voxel-wise results were evaluated for statistical significance (p < 0.05) after adjustment for multiple comparisons. Carotid IMT in the type 2 diabetes group was correlated with CBF. RESULTS Compared to obese controls, the type 2 diabetes group had significantly lower global CBF (49.7 ± 7.2 vs. 63.8 ± 11.5 ml/gm/min, p < 0.001). Significantly lower CBF was observed in multiple brain regions for the type 2 diabetes group, while no regions with higher CBF were identified. In the type 2 diabetes group, carotid IMT was inversely correlated with CBF, both globally (r = -0.70, p = 0.002) and in regional clusters. CONCLUSIONS In this pilot study, lower CBF was seen in youth with type 2 diabetes compared to youth with obesity and IMT was inversely correlated with CBF. Cerebrovascular impairment may be present in youth with type 2 diabetes. These findings could represent a mechanistic link to explain previously reported brain volume and neurocognitive differences.
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Affiliation(s)
- Jacob M Redel
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.,Division of Endocrinology, Children's Mercy Hospital, Kansas City, Missouri, USA
| | - Mark DiFrancesco
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Gregory R Lee
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Adi Ziv
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Adolescent Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Adolescent Medicine Unit, Department of Day Care Hospitalization, Schneider Children's Hospital Medical Center of Israel, Petah Tikva, Israel
| | - Lawrence M Dolan
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Cassandra C Brady
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.,Division of Endocrinology and Diabetes, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA
| | - Amy S Shah
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.,Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
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27
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Anita NZ, Zebarth J, Chan B, Wu CY, Syed T, Shahrul D, Nguyen MM, Pakosh M, Herrmann N, Lanctôt KL, Swardfager W. Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis. Brain Behav Immun 2022; 100:55-69. [PMID: 34808290 DOI: 10.1016/j.bbi.2021.11.005] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 11/01/2021] [Accepted: 11/13/2021] [Indexed: 12/15/2022] Open
Abstract
People with type 2 diabetes mellitus (T2DM) are at increased risk of mild cognitive impairment and dementia. Systemic inflammation has been proposed as a common risk factor. This study aimed to summarize the clinical data pertaining to peripheral blood inflammatory markers. We identified original peer-reviewed articles reporting blood inflammatory marker concentrations in groups of people with a T2DM diagnosis who have cognitive impairment (CI; including mild cognitive impairment, Alzheimer's disease, vascular cognitive impairment) vs. normal cognition (NC). Between-group standardized mean differences (SMD) were summarized in random effects meta-analyses. From 2108 records, data were combined quantitatively from 40 studies. Concentrations of interleukin-6 (IL-6; NCI/NNC = 934/3154, SMD 0.74 95% confidence interval [0.07, 1.42], Z5 = 2.15, p = 0.03; I2 = 98.08%), C-reactive protein (CRP; NCI/NNC = 1610/4363, SMD 0.80 [0.50, 1.11], Z14 = 5.25, p < 0.01; I2 = 94.59%), soluble vascular cell adhesion molecule-1 (sVCAM-1; NCI/NNC = 104/1063, SMD 1.64 95% confidence interval [0.21, 3.07], Z2 = 2.25, p = 0.02; I2 = 95.19%), and advanced glycation end products (AGEs; NCI/NNC = 227/317, SMD 0.84 95% confidence interval [0.41, 1.27], Z2 = 3.82, p < 0.01; I2 = 81.07%) were higher among CI groups compared to NC. Brain derived neurotropic factor (BDNF) concentrations were significantly lower in CI compared to NC (NCI/NNC = 848/2063, SMD -0.67 95% confidence interval [-0.99, -0.35], Z3 = -4.09, p < 0.01; I2 = 89.20%). Cognitive impairment among people with T2DM was associated with systemic inflammation and lower BDNF concentrations. These inflammatory characteristics support an increased inflammatory-vascular interaction associated with cognitive impairment in T2DM. PROSPERO (CRD42020188625).
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Affiliation(s)
- Natasha Z Anita
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada; Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; University Health Network Toronto Rehabilitation Institute - Rumsey Centre Cardiac Rehabilitation, 347 Rumsey Rd, East York, Ontario M4G 2V6, Canada
| | - Julia Zebarth
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada; Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; University Health Network Toronto Rehabilitation Institute - Rumsey Centre Cardiac Rehabilitation, 347 Rumsey Rd, East York, Ontario M4G 2V6, Canada
| | - Brian Chan
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada
| | - Che-Yuan Wu
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada; Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
| | - Taha Syed
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada
| | - Dinie Shahrul
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada
| | - Michelle M Nguyen
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada; Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; University Health Network Toronto Rehabilitation Institute - Rumsey Centre Cardiac Rehabilitation, 347 Rumsey Rd, East York, Ontario M4G 2V6, Canada
| | - Maureen Pakosh
- Library & Information Services, University Health Network- Toronto Rehabilitation Institute, Toronto, Ontario, Canada
| | - Nathan Herrmann
- Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada
| | - Krista L Lanctôt
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada; Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; University Health Network Toronto Rehabilitation Institute - Rumsey Centre Cardiac Rehabilitation, 347 Rumsey Rd, East York, Ontario M4G 2V6, Canada
| | - Walter Swardfager
- Department of Pharmacology & Toxicology - University of Toronto, Medical Sciences Building, 1 King's College Circle Room 4207, Toronto, Ontario M5S 1A8, Canada; Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada; University Health Network Toronto Rehabilitation Institute - Rumsey Centre Cardiac Rehabilitation, 347 Rumsey Rd, East York, Ontario M4G 2V6, Canada.
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28
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Zhang W, Lu J, Qing Z, Zhang X, Zhao H, Bi Y, Zhang B. Effects of Subcortical Atrophy and Alzheimer’s Pathology on Cognition in Elderly Type 2 Diabetes: The Alzheimer’s Disease Neuroimaging Initiative Study. Front Aging Neurosci 2022; 14:781938. [PMID: 35173604 PMCID: PMC8841716 DOI: 10.3389/fnagi.2022.781938] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 01/05/2022] [Indexed: 12/03/2022] Open
Abstract
Background Subcortical atrophy and increased cerebral β-amyloid and tau deposition are linked to cognitive decline in type 2 diabetes. However, whether and how subcortical atrophy is related to Alzheimer’s pathology in diabetes remains unclear. This study therefore aimed to investigate subcortical structural alterations induced by diabetes and the relationship between subcortical alteration, Alzheimer’s pathology and cognition. Methods Participants were 150 patients with type 2 diabetes and 598 propensity score-matched controls without diabetes from the Alzheimer’s Disease Neuroimaging Initiative. All subjects underwent cognitive assessments, magnetic resonance imaging (MRI), and apolipoprotein E (ApoE) genotyping, with a subset that underwent amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) assays to determine cerebral β-amyloid deposition (n = 337) and CSF p-tau (n = 433). Subcortical structures were clustered into five modules based on Pearson’s correlation coefficients of volumes across all subjects: the ventricular system, the corpus callosum, the limbic system, the diencephalon, and the striatum. Using structural equation modeling (SEM), we investigated the relationships among type 2 diabetes, subcortical structural alterations, and AD pathology. Results Compared with the controls, the diabetic patients had significant reductions in the diencephalon and limbic system volumes; moreover, patients with longer disease duration (>6 years) had more severe volume deficit in the diencephalon. SEM suggested that type 2 diabetes, age, and the ApoE ε4 allele (ApoE-ε4) can affect cognition via reduced subcortical structure volumes (total effect: age > ApoE-ε4 > type 2 diabetes). Among them, age and ApoE-ε4 strongly contributed to AD pathology, while type 2 diabetes neither directly nor indirectly affected AD biomarkers. Conclusion Our study suggested the subcortical atrophy mediated the association of type 2 diabetes and cognitive decline. Although both type 2 diabetes and AD are correlated with subcortical neurodegeneration, type 2 diabetes have no direct or indirect effect on the cerebral amyloid deposition and CSF p-tau.
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Affiliation(s)
- Wen Zhang
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jiaming Lu
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhao Qing
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xin Zhang
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Hui Zhao
- Department of Neurology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yan Bi
- Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Bing Zhang
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- *Correspondence: Bing Zhang,
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29
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Choi EY, Park YW, Lee M, Kim M, Lee CS, Ahn SS, Kim J, Lee SK. Magnetic Resonance Imaging-Visible Perivascular Spaces in the Basal Ganglia Are Associated With the Diabetic Retinopathy Stage and Cognitive Decline in Patients With Type 2 Diabetes. Front Aging Neurosci 2021; 13:666495. [PMID: 34867262 PMCID: PMC8633948 DOI: 10.3389/fnagi.2021.666495] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 10/13/2021] [Indexed: 01/14/2023] Open
Abstract
Purpose: The aim of this study was to evaluate whether perivascular space (PVS) severity and retinal ganglion cell layer (GCL) thickness differed based on the stage of diabetic retinopathy (DR) and the cognitive status in patients with DR. Methods: A total of 81 patients with DR (51 in the non-proliferative group and 30 in the proliferative group) were included in this retrospective, cross-sectional study. PVS severity was assessed in the basal ganglia (BG) and centrum semiovale using MRI. The total cerebral small vessel disease (SVD) score was determined based on the numbers of lacunes and microbleeds and the severity of white matter hyperintensity. Optical coherence tomography was used to measure foveal and perifoveal GCL thicknesses. Cerebral SVD markers and cognitive function were compared between the groups, and correlations between the BG-PVS severity and the Mini-Mental Status Examination (MMSE) scores and GCL parameters were evaluated. Results: Patients with proliferative DR had higher BG-PVS severity (P = 0.012), higher total cerebral SVD scores (P = 0.035), reduced GCL thicknesses in the inferior (P = 0.027), superior (P = 0.046), and temporal (P = 0.038) subfields compared to patients with non-proliferative DR. In addition, the BG-PVS severity was negatively correlated with the MMSE score (P = 0.007), and the GCL thickness was negatively correlated with the BG-PVS severity (P-values < 0.05 for inferior, superior, and temporal subfields). Conclusion: BG-PVS severity and retinal GCL thickness may represent novel imaging biomarkers reflecting the stage of DR and cognitive decline in diabetic patients. Furthermore, these results suggest a possible link between cerebral and retinal neurodegeneration at the clinical level.
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Affiliation(s)
- Eun Young Choi
- Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea
| | - Yae Won Park
- Department of Radiology, Center for Clinical Imaging Data Science, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Minyoung Lee
- Department of Endocrinology, Yonsei University College of Medicine, Seoul, South Korea
| | - Min Kim
- Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea
| | | | - Sung Soo Ahn
- Department of Radiology, Center for Clinical Imaging Data Science, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Jinna Kim
- Department of Radiology, Center for Clinical Imaging Data Science, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung-Koo Lee
- Department of Radiology, Center for Clinical Imaging Data Science, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea
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30
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Comparison of Mini-Mental State Examination and Addenbrooke’s Cognitive Examination III in detection of cognitive impairment in patients with type 2 diabetes. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-01012-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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31
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Ozato N, Saitou S, Yamaguchi T, Katashima M, Misawa M, Jung S, Mori K, Kawada H, Katsuragi Y, Mikami T, Nakaji S. Association between Visceral Fat and Brain Structural Changes or Cognitive Function. Brain Sci 2021; 11:brainsci11081036. [PMID: 34439655 PMCID: PMC8391376 DOI: 10.3390/brainsci11081036] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 07/29/2021] [Accepted: 08/02/2021] [Indexed: 01/16/2023] Open
Abstract
Visceral fat accumulation is an independent risk factor for cardiovascular disease and mortality. Visceral fat is a causal risk factor for hypertension and type 2 diabetes, which was reported as one of the risk factors for dementia. Visceral fat areas (VFA) might be clinically important to prevent dementia; however, the association between VFA and cognitive function in the elderly remains unknown. We aimed to evaluate the association between brain structural abnormalities using magnetic resonance imaging (MRI) and VFA, and the association between cognitive function and VFA, in the elderly. A total of 2364 healthy individuals were enrolled, and we excluded those diagnosed with dementia. Participants were divided into a high-VFA and a low-VFA group based on median VFA. The high-VFA group had significantly lower cognitive function than the low-VFA group (p = 0.025), after adjustment for related factors using a linear regression model. Regarding brain structure in MRI, VFA remained significantly associated with white matter lesions (odds ratio (OR), 1.90; 95% confidence interval (1.33-2.70); adjusted p < 0.001) and perivascular space (OR, 1.28; 95% confidence interval (1.02-1.61); adjusted p = 0.033). Further follow-up studies are needed, but reducing visceral fat might be important, not only to prevent cardiovascular disease but also to prevent dementia.
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Affiliation(s)
- Naoki Ozato
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (M.K.); (K.M.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan; (T.Y.); (H.K.)
- Correspondence: ; Tel.: +81-(0)172-39-5041
| | - Shinnichiro Saitou
- Biological Science Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan;
| | - Tohru Yamaguchi
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan; (T.Y.); (H.K.)
| | - Mitsuhiro Katashima
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (M.K.); (K.M.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan; (T.Y.); (H.K.)
| | - Mina Misawa
- COI Research Initiatives Organization, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (M.M.); (S.J.)
| | - Songee Jung
- COI Research Initiatives Organization, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (M.M.); (S.J.)
| | - Kenta Mori
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (M.K.); (K.M.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan; (T.Y.); (H.K.)
| | - Hiromitsu Kawada
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan; (T.Y.); (H.K.)
| | - Yoshihisa Katsuragi
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (M.K.); (K.M.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan; (T.Y.); (H.K.)
| | - Tatsuya Mikami
- Innovation Center for Health Promotion, Hirosaki University Graduate School of Medicine, Hirosaki City 036-8562, Japan;
| | - Shigeyuki Nakaji
- Department of Social Medicine, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan;
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32
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Bergantin LB. Diabetes and inflammatory diseases: An overview from the perspective of Ca 2+/3'-5'-cyclic adenosine monophosphate signaling. World J Diabetes 2021; 12:767-779. [PMID: 34168726 PMCID: PMC8192245 DOI: 10.4239/wjd.v12.i6.767] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 12/29/2020] [Accepted: 03/07/2021] [Indexed: 02/06/2023] Open
Abstract
A large amount of evidence has supported a clinical link between diabetes and inflammatory diseases, e.g., cancer, dementia, and hypertension. In addition, it is also suggested that dysregulations related to Ca2+ signaling could link these diseases, in addition to 3'-5'-cyclic adenosine monophosphate (cAMP) signaling pathways. Thus, revealing this interplay between diabetes and inflammatory diseases may provide novel insights into the pathogenesis of these diseases. Publications involving signaling pathways related to Ca2+ and cAMP, inflammation, diabetes, dementia, cancer, and hypertension (alone or combined) were collected by searching PubMed and EMBASE. Both signaling pathways, Ca2+ and cAMP signaling, control the release of neurotransmitters and hormones, in addition to neurodegeneration, and tumor growth. Furthermore, there is a clear relationship between Ca2+ signaling, e.g., increased Ca2+ signals, and inflammatory responses. cAMP also regulates pro- and anti-inflammatory responses. Due to the experience of our group in this field, this article discusses the role of Ca2+ and cAMP signaling in the correlation between diabetes and inflammatory diseases, including its pharmacological implications. As a novelty, this article also includes: (1) A timeline of the major events in Ca2+/cAMP signaling; and (2) As coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving situation, this article also discusses recent reports on the role of Ca2+ channel blockers for preventing Ca2+ signaling disruption due to COVID-19, including the correlation between COVID-19 and diabetes.
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33
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High burden of cerebral white matter lesion in 9 Asian cities. Sci Rep 2021; 11:11587. [PMID: 34078946 PMCID: PMC8172636 DOI: 10.1038/s41598-021-90746-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 05/13/2021] [Indexed: 12/19/2022] Open
Abstract
Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer's disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.
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34
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Sungura R, Onyambu C, Mpolya E, Sauli E, Vianney JM. The extended scope of neuroimaging and prospects in brain atrophy mitigation: A systematic review. INTERDISCIPLINARY NEUROSURGERY 2021. [DOI: 10.1016/j.inat.2020.100875] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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35
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Sundermann EE, Thomas KR, Bangen KJ, Weigand AJ, Eppig JS, Edmonds EC, Wong CG, Bondi MW, Delano-Wood L. Prediabetes Is Associated With Brain Hypometabolism and Cognitive Decline in a Sex-Dependent Manner: A Longitudinal Study of Nondemented Older Adults. Front Neurol 2021; 12:551975. [PMID: 33679574 PMCID: PMC7933503 DOI: 10.3389/fneur.2021.551975] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 01/25/2021] [Indexed: 11/13/2022] Open
Abstract
Although type 2 diabetes is a well-known risk factor for Alzheimer's disease (AD), little is known about how its precursor-prediabetes-impacts neuropsychological function and brain health. Thus, we examined the relationship between prediabetes and AD-related biological and cognitive/clinical markers in a well-characterized sample drawn from the Alzheimer's Disease Neuroimaging Initiative. Additionally, because women show higher rates of AD and generally more atherogenic lipid profiles than men, particularly in the context of diabetes, we examined whether sex moderates any observed associations. The total sample of 911 nondemented and non-diabetic participants [normal control = 540; mild cognitive impairment (MCI) = 371] included 391 prediabetic (fasting blood glucose: 100-125 mg/dL) and 520 normoglycemic individuals (age range: 55-91). Linear mixed effects models, adjusted for demographics and vascular and AD risk factors, examined the independent and interactive effects of prediabetes and sex on 2-6 year trajectories of FDG-PET measured cerebral metabolic glucose rate (CMRglu), hippocampal/intracranial volume ratio (HV/IV), cerebrospinal fluid phosphorylated tau-181/amyloid-β1-42 ratio (p-tau181/Aβ1-42), cognitive function (executive function, language, and episodic memory) and the development of dementia. Analyses were repeated in the MCI subsample. In the total sample, prediabetic status had an adverse effect on CMRglu across time regardless of sex, whereas prediabetes had an adverse effect on executive function across time in women only. Within the MCI subsample, prediabetic status was associated with lower CMRglu and poorer executive function and language performance across time within women, whereas these associations were not seen within men. In the total sample and MCI subsample, prediabetes did not relate to HV/IV, p-tau181/Aβ1-42, memory function or dementia risk regardless of sex; however, among incident dementia cases, prediabetic status related to earlier age of dementia onset in women but not in men. Results suggest that prediabetes may affect cognition through altered brain metabolism, and that women may be more vulnerable to the negative effects of glucose intolerance.
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Affiliation(s)
- Erin E Sundermann
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States
| | - Kelsey R Thomas
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.,Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
| | - Katherine J Bangen
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.,Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
| | - Alexandra J Weigand
- San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, United States
| | - Joel S Eppig
- San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, United States
| | - Emily C Edmonds
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.,Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
| | - Christina G Wong
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.,Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
| | - Mark W Bondi
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.,Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
| | - Lisa Delano-Wood
- Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.,Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
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36
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Li C, Jin R, Liu K, Li Y, Zuo Z, Tong H, Zhang J, Zhang J, Guo Y, Lai Y, Sun J, Wang J, Xiong K, Chen X. White Matter Atrophy in Type 2 Diabetes Mellitus Patients With Mild Cognitive Impairment. Front Neurosci 2021; 14:602501. [PMID: 33536867 PMCID: PMC7848149 DOI: 10.3389/fnins.2020.602501] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/21/2020] [Indexed: 01/21/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) patients are highly susceptible to developing dementia, especially for those with mild cognitive impairment (MCI), but its underlying cause is still unclear. In this study, we performed a battery of neuropsychological tests and high-resolution sagittal T1-weighted structural imaging to explore how T2DM affects white matter volume (WMV) and cognition in 30 T2DM-MCI patients, 30 T2DM with normal cognition (T2DM-NC) patients, and 30 age-, sex-, and education-matched healthy control (HC) individuals. The WMV of the whole brain was obtained with automated segmentation methods. Correlations between the WMV of each brain region and neuropsychological tests were analyzed in the T2DM patients. The T2DM-NC patients and HC individuals did not reveal any significant differences in WMV. Compared with the T2DM-NC group, the T2DM-MCI group showed statistically significant reduction in the WMV of seven brain regions, mainly located in the frontotemporal lobe and limbic system, five of which significantly correlated with Montreal Cognitive Assessment (MoCA) scores. Subsequently, we evaluated the discriminative ability of these five regions for MCI in T2DM patients. The WMV of four regions, including left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus had high diagnostic value for MCI detection in T2DM patients (AUC > 0.7). Among these four regions, left precuneus WMV presented the best diagnostic value (AUC: 0.736; sensitivity: 70.00%; specificity: 73.33%; Youden index: 0.4333), but with no significant difference relative to the minimum AUC. In conclusion, T2DM could give rise to the white matter atrophy of several brain regions. Each WMV of left posterior cingulate, precuneus, insula, and right rostral middle frontal gyrus could be an independent imaging biomarker to detect cognitive impairment at the early stage in T2DM patients and play an important role in its pathophysiological mechanism.
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Affiliation(s)
- Chang Li
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.,Department of Radiology, Southwest Hospital, Army Medical University, Chongqing, China
| | - Rongbing Jin
- Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, China.,Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, China
| | - Kaijun Liu
- Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China
| | - Yang Li
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China
| | - Zhiwei Zuo
- Department of Radiology, General Hospital of Western Theater Command, Chengdu, China
| | - Haipeng Tong
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.,Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, China
| | - Jingna Zhang
- Department of Medical Imaging, College of Biomedical Engineering, Army Medical University, Chongqing, China
| | - Junfeng Zhang
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.,Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, China
| | - Yu Guo
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China
| | - Yuqi Lai
- School of Foreign Languages and Cultures, Chongqing University, Chongqing, China
| | - Jinju Sun
- Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, China
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Army Medical University, Chongqing, China
| | - Kunlin Xiong
- Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.,Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, China
| | - Xiao Chen
- Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, China.,Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing, China
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37
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Guicciardi M, Fadda D, Fanari R, Doneddu A, Crisafulli A. Affective Variables and Cognitive Performances During Exercise in a Group of Adults With Type 2 Diabetes Mellitus. Front Psychol 2021; 11:611558. [PMID: 33424722 PMCID: PMC7785934 DOI: 10.3389/fpsyg.2020.611558] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 11/27/2020] [Indexed: 11/19/2022] Open
Abstract
Previous research has documented that type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. Psychological variables were repeatedly investigated to understand why T2DM patients are poorly active, despite standards of medical care recommends performing aerobic and resistance exercise regularly and reducing the amount of time spent sitting. This exploratory study aims to investigate how affective variables as thoughts, feelings, and individuals’ stage of exercise adoption can modulate low cognitive performances during an experimental procedure based on exercise. The Exercise Thoughts Questionnaire (ETQ), Exercise-Induced Feeling Scale (EFI), and Physical Activity Stage of Change were administered to a sample of 12 T2DM patients. The Bivalent Shape Task (BST) alone (BST), BST with exercise [control exercise recovery (CER) + BST], and BST with metaboreflex [post-exercise muscle ischemia (PEMI) + BST] were used as mental task, and response time to congruent, incongruent, and neutral stimuli was recorded. Concomitant cerebral oxygenation (COX) was evaluated by near-infrared spectroscopy (NIRS). As expected, T2DM patients performed significantly better when the stimulus was presented in congruent trials (followed by neutral and incongruent). In the CER + BST session, T2DM patients showed longer reaction time to incongruent trials than in the PEMI + BST and BST alone sessions. Positive feelings toward exercise seem to modulate cognitive performances in high challenging task only if T2DM patients were conscious to play exercise. These results could provide some insights for health intervention targeting exercise for patients with T2DM in order to enhance cognitive performances.
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Affiliation(s)
- Marco Guicciardi
- Department of Education, Psychology, Philosophy, University of Cagliari, Cagliari, Italy
| | - Daniela Fadda
- Department of Education, Psychology, Philosophy, University of Cagliari, Cagliari, Italy
| | - Rachele Fanari
- Department of Education, Psychology, Philosophy, University of Cagliari, Cagliari, Italy
| | - Azzurra Doneddu
- Sports Physiology Laboratory, University of Cagliari, Cagliari, Italy
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Wang HK, Huang CY, Chen YW, Sun YT. Hyperglycemia compromises the ischemia-provoked dedifferentiation of cerebral pericytes through p21-SOX2 signaling in high-fat diet-induced murine model. Diab Vasc Dis Res 2021; 18:1479164121990641. [PMID: 33557613 PMCID: PMC8482726 DOI: 10.1177/1479164121990641] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
AIM Diabetes-related cerebral small vessel disease (CSVD) causes neurological deficits. Patients with diabetes showed pericyte loss as a hallmark of retinopathy. Cerebral pericytes, which densely localize around brain capillaries, are quiescent stem cells regulating regeneration of brain and may have a role in CSVD development. This study investigated whether diabetes impairs ischemia-provoked dedifferentiation of pericytes. METHODS A murine high-fat diet (HFD)-induced diabetes model was used. After cerebral ischemia induction in the mice, pericytes were isolated and grown for a sphere formation assay. RESULTS The sphere counts from the HFD group were lower than those in the chow group. As the spheres formed, pericyte marker levels decreased and SOX2 levels increased gradually in the chow group, but not in the HFD group. Before sphere formation, pericytes from the HFD group showed high p21 levels. The use of a p21 inhibitor rescued the reduction of sphere counts in the HFD group. At cellular level, hyperglycemia-induced ROS increased the level of p21 in cerebral pericytes. The p21-SOX2 signaling was then activated after oxygen-glucose deprivation. CONCLUSION HFD-induced diabetes compromises the stemness of cerebral pericytes by altering p21-SOX2 signaling. These results provide evidence supporting the role of pericytes in diabetes-related CSVD and subsequent cerebral dysfunction.
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Affiliation(s)
- Hao-Kuang Wang
- School of Medicine for International Students, I-Shou University, Kaohsiung
- Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung
| | - Chih-Yuan Huang
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
| | - Yun-Wen Chen
- Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan
| | - Yuan-Ting Sun
- Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
- Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan
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Lawson CM, Rentrup KFG, Cai X, Kulkarni PP, Ferris CF. Using multimodal MRI to investigate alterations in brain structure and function in the BBZDR/Wor rat model of type 2 diabetes. Animal Model Exp Med 2020; 3:285-294. [PMID: 33532703 PMCID: PMC7824967 DOI: 10.1002/ame2.12140] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 09/13/2020] [Accepted: 09/21/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND This is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was hypothesized there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with noninvasive MRI. METHODS The transgenic BBZDR/Wor rat, an animal model of T2MD, and age-matched controls were studied for changes in brain structure using voxel-based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting-state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site-specific data on over 168 different brain areas. RESULTS There was an overall reduction in brain volume focused primarily on the somatosensory cortex, cerebellum, and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus. CONCLUSION The neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods did not reflect those reported for T2DB patients in the clinic. The data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.
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Affiliation(s)
| | | | - Xuezhu Cai
- Center for Translational NeuroImagingNortheastern UniversityBostonMAUSA
| | | | - Craig F. Ferris
- Center for Translational NeuroImagingNortheastern UniversityBostonMAUSA
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Baptista MG, Ferreira CG, Albuquerque YM, D’assunção CG, Alves RC, Wanderley-Teixeira V, Teixeira ÁA. Histomorphometric and immunohistochemical evaluation of the frontal cerebral cortex in diabetic rats after treatment with melatonin. PESQUISA VETERINÁRIA BRASILEIRA 2020; 40:1077-1087. [DOI: 10.1590/1678-5150-pvb-6421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
ABSTRACT: The central nervous system is vulnerable to complications caused by diabetes. These complications lead to increased oxidative stress in the brain, resulting in damage to the cerebral cortex, among other regions. Insulin and hypoglycemic agents are still the most widely used treatments. However, current research with an experimental model of diabetes suggests the use of antioxidants, such as melatonin. Thus, we tested the hypothesis that exogenous melatonin may decrease or prevent the effects of diabetes in the frontal cortex of the rat brain. Fifty albino rats were allocated into five groups: GC = rats without diabetes induction, GD = diabetic rats induced by streptozotocin, GDM = streptozotocin-induced and melatonin-treated diabetic rats, GDI = diabetic rats induced by streptozotocin and treated with insulin, GDMI = diabetic rats induced by streptozotocin and treated with melatonin and insulin simultaneously. Diabetes was induced by intraperitoneal administration of streptozotocin (60mg/kg). Insulin (5U/day) was administered subcutaneously and melatonin (10mg/kg) by drinking water; both treatments last days after. We analyzed animals’ weight, the cytokines IL-6 and TNF-α, apoptosis, glycogen, and did morphometry and histopathology of the frontal cortex were analyzed. The results showed that the cerebral cortex of the diabetic animals presented axonal degeneration, reduced number of neurons in the cortex, reduced glycogen, increased IL-6 and TNF-α expression, high apoptotic index, and reduced animal weight and the brain. Treatment with melatonin associated or not with insulin prevented such effects. Thus, we conclude that melatonin associated with insulin may be an alternative for avoiding the impact of diabetes in the brain’s frontal cortex.
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Spatial patterns of correlation between cortical amyloid and cortical thickness in a tertiary clinical population with memory deficit. Sci Rep 2020; 10:20717. [PMID: 33244036 PMCID: PMC7693188 DOI: 10.1038/s41598-020-77503-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 11/11/2020] [Indexed: 12/28/2022] Open
Abstract
To estimate regional Alzheimer disease (AD) pathology burden clinically, analysis methods that enable tracking brain amyloid or tau positron emission tomography (PET) with magnetic resonance imaging (MRI) measures are needed. We therefore developed a robust MRI analysis method to identify brain regions that correlate linearly with regional amyloid burden in congruent PET images. This method was designed to reduce data variance and improve the sensitivity of the detection of cortical thickness-amyloid correlation by using whole brain modeling, nonlinear image coregistration, and partial volume correction. Using this method, a cross-sectional analysis of 75 tertiary memory clinic AD patients was performed to test our hypothesis that regional amyloid burden and cortical thickness are inversely correlated in medial temporal neocortical regions. Medial temporal cortical thicknesses were not correlated with their regional amyloid burden, whereas cortical thicknesses in the lateral temporal, lateral parietal, and frontal regions were inversely correlated with amyloid burden. This study demonstrates the robustness of our technique combining whole brain modeling, nonlinear image coregistration, and partial volume correction to track the differential correlation between regional amyloid burden and cortical thinning in specific brain regions. This method could be used with amyloid and tau PET to assess corresponding cortical thickness changes.
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Cardiometabolic determinants of early and advanced brain alterations: Insights from conventional and novel MRI techniques. Neurosci Biobehav Rev 2020; 115:308-320. [DOI: 10.1016/j.neubiorev.2020.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/21/2020] [Accepted: 04/02/2020] [Indexed: 12/11/2022]
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Li M, Huang L, Yang D, Luo C, Qin R, Zhang B, Zhao H, Xu Y. Atrophy patterns of hippocampal subfields in T2DM patients with cognitive impairment. Endocrine 2020; 68:536-548. [PMID: 32172485 PMCID: PMC7308251 DOI: 10.1007/s12020-020-02249-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 02/26/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To identify the volume changes of hippocampus subfields in T2DM patients with cognitive impairment and to determine how these atrophy patterns associate with impairments in different cognitive domain. METHODS A total of 117 individuals were recruited, including T2DM patients with cognitive impairment (T2DM-CI) (n = 34), T2DM patients without cognitive impairment (T2DM-non-CI) (n = 36) and normal controls (NC) (n = 47). All subjects went through a 3.0 T magnetic resonance (MR) scan and a neuropsychological assessment. Hippocampal subfield volumes were processed using the FreeSurfer 6.0.0 and compared among the three groups. Partial correlation analyses were used to estimate the relationship between cognitive function and hippocampal subfield volume, with age, sex, education, and eTIV (estimated total intracranial volume) as covariants. RESULTS The total hippocampal volume had a reduction trend among the three groups, and the significantly statistical difference only was found between T2DM-CI group and NC group. Regarding the hippocampal subfields, the volumes of left subiculum, left presubiculum, left fimbria, right CA1 and right molecular layer HP decreased significantly in the T2DM-CI group (P < 0.05/12). Partial correlation analyses showed that the volumes of the left subiculum, left fimbria, and left presubiculum were significantly related to executive function. The right hippocampal CA1 volume was significantly correlated with memory in the T2DM-CI group (P < 0.05). But in T2DM-non-CI group, the correlation between the left fimbria volume and the memory, the left subiculum volume and MoCA were different with the T2DM-CI group and NC group (P < 0.05). CONCLUSIONS The smaller the volume of left presubiculum, the worse the executive function, and the atrophy of the right CA1 was related to memory impairment in T2DM-CI group. However the result was the opposite in T2DM-non-CI group. There might be a compensation mechanism of hippocampus of T2DM patients before cognitive impairment.
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Affiliation(s)
- MengChun Li
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China
- Nanjing Medicine Center For Neurological and Psychiatric Diseases, Nanjing, China
| | - LiLi Huang
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China
- Nanjing Medicine Center For Neurological and Psychiatric Diseases, Nanjing, China
| | - Dan Yang
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China
- Nanjing Medicine Center For Neurological and Psychiatric Diseases, Nanjing, China
| | - CaiMei Luo
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China
- Nanjing Medicine Center For Neurological and Psychiatric Diseases, Nanjing, China
| | - RuoMeng Qin
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China
- Nanjing Medicine Center For Neurological and Psychiatric Diseases, Nanjing, China
| | - Bing Zhang
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China
- Department of Radiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China
| | - Hui Zhao
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China.
- Nanjing Medicine Center For Neurological and Psychiatric Diseases, Nanjing, China.
| | - Yun Xu
- Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
- Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, China.
- Nanjing Medicine Center For Neurological and Psychiatric Diseases, Nanjing, China.
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Abstract
Tau protein which was discovered in 1975 [310] became of great interest when it was identified as the main component of neurofibrillary tangles (NFT), a pathological feature in the brain of patients with Alzheimer's disease (AD) [39, 110, 232]. Tau protein is expressed mainly in the brain as six isoforms generated by alternative splicing [46, 97]. Tau is a microtubule associated proteins (MAPs) and plays a role in microtubules assembly and stability, as well as diverse cellular processes such as cell morphogenesis, cell division, and intracellular trafficking [49]. Additionally, Tau is involved in much larger neuronal functions particularly at the level of synapses and nuclei [11, 133, 280]. Tau is also physiologically released by neurons [233] even if the natural function of extracellular Tau remains to be uncovered (see other chapters of the present book).
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Youssef MM, Abd El-Latif HA, El-Yamany MF, Georgy GS. Aliskiren and captopril improve cognitive deficits in poorly controlled STZ-induced diabetic rats via amelioration of the hippocampal P-ERK, GSK3β, P-GSK3β pathway. Toxicol Appl Pharmacol 2020; 394:114954. [PMID: 32171570 DOI: 10.1016/j.taap.2020.114954] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 03/08/2020] [Accepted: 03/10/2020] [Indexed: 12/22/2022]
Abstract
Learning and memory deficits are obvious symptoms that develop over time in patients with poorly controlled diabetes. Hyperactivity of the renin-angiotensin system (RAS) is directly associated with β-cell dysfunction and diabetic complications, including cognitive impairment. Here, we investigated the protective and molecular effects of two RAS modifiers, aliskiren; renin inhibitor and captopril; angiotensin converting enzyme inhibitor, on cognitive deficits in the rat hippocampus. Injection of low dose streptozotocin for 4 days resulted in type 1 diabetes. Then, poorly controlled diabetes was mimicked with ineffective daily doses of insulin for 4 weeks. The hyperglycaemia and pancreatic atrophy caused memory disturbance that were identifiable in behavioural tests, hippocampal neurodegeneration, and the following significant changes in the hippocampus, increases in the inflammatory marker interleukin 1β, cholinesterase, the oxidative stress marker malondialdehyde and protein expression of phosphorylated extracellular-signal-regulated kinase and glycogen synthase kinase-3 beta versus decrease in the antioxidant reduced glutathione and protein expression of phosphorylated glycogen synthase kinase-3 beta. Blocking RAS with either drugs along with insulin amended all previously mentioned parameters. Aliskiren stabilized the blood glucose level and restored normal pancreatic integrity and hippocampal malondialdehyde level. Aliskiren showed superior protection against the hippocampal degeneration displayed in the earlier behavioural modification in the passive avoidance test, and the aliskiren group outperformed the control group in the novel object recognition test. We therefore conclude that aliskiren and captopril reversed the diabetic state and cognitive deficits in rats with poorly controlled STZ-induced diabetes through reducing oxidative stress and inflammation and modulating protein expression.
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Affiliation(s)
- Madonna M Youssef
- Department of Pharmacology, National organization for drug control and research (NODCAR), Giza, Egypt.
| | - H A Abd El-Latif
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo 11562, Egypt
| | - M F El-Yamany
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St, Cairo 11562, Egypt
| | - Gehan S Georgy
- Department of Pharmacology, National organization for drug control and research (NODCAR), Giza, Egypt
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Zhang L, Mao H. The Relationship Between Serum VCAM-1 and Alzheimer's Disease in Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2020; 13:4661-4667. [PMID: 33299334 PMCID: PMC7721106 DOI: 10.2147/dmso.s274232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 10/23/2020] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Previous studies have reported that diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD). Vascular cell adhesion molecule-1 (VCAM-1) plays an important role in the pathological process of atherosclerosis. The aim was to elucidate the relationship between serum VCAM-1 and early AD in DM patients. METHODS Serum samples for VCAM-1 were tested in 208 DM patients. All included DM patients were followed up for a median of 36 months prospectively. The prognostic value of serum VCAM-1 for predicting AD events was analyzed by using Cox proportional hazard. RESULTS Serum VCAM-1 was independently associated with AD history after adjusting for related confounding factors in patients with DM at baseline by using the logistic regression analysis (OR=1.861; 95% CI, 1.435-2.539; P trend=0.020). The Cox proportional hazard model suggested that VCAM-1 was a prognostic factor for AD events in the DM patients (HR=2.728; 95% CI, 1.785-5.439; P trend<0.001). Stratified analysis showed that the significant association between AD event and serum VCAM-1 in DM patients was not affective by CVD history. CONCLUSION Our results showed that higher VCAM-1 levels were significantly related to a higher risk of AD events in DM patients. The serum biomarker might be beneficial to predict AD early. Serum VCAM-1 might be a good biochemical parameter for predicting AD in DM.
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Affiliation(s)
- Lingyun Zhang
- Department of Laboratory Medicine, Zutangshan Hospital, Nanjing211153, Jiangsu, People’s Republic of China
| | - Huawu Mao
- Department of Neurology, Taizhou Second People’s Hospital, Taizhou225500, Jiangsu, People’s Republic of China
- Correspondence: Huawu MaoDepartment of Neurology, Taizhou Second People’s Hospital, NO. 27 Jiankang Road, Jiangyan District, Taizhou City225500, Jiangsu, People’s Republic of ChinaTel +86 52388245686 Email
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Bergantin LB. A Link Between Brain Insulin Resistance and Cognitive Dysfunctions: Targeting Ca2+/cAMP Signalling. Cent Nerv Syst Agents Med Chem 2020; 20:103-109. [PMID: 31995022 DOI: 10.2174/1871524920666200129121232] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 06/04/2020] [Accepted: 06/06/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND A correlation between cognitive dysfunctions and brain insulin resistance has been established by several clinical and experimental studies. Consistent data support that people diagnosed with brain insulin resistance, resulted from diabetes, have shown an increased risk of presenting cognitive dysfunctions, clinical signs of dementia and depression, then speculating a role of dysregulations related to insulin signalling in these diseases. Furthermore, it is currently discussed that Ca2+ signalling, and its dysregulations, may be a factor which could correlate with brain insulin resistance and cognitive dysfunctions. OBJECTIVE Following this, revealing this interplay between these diseases may provide novel insights into the pathogenesis of such diseases. METHODS Publications covering topics such as Ca2+ signalling, diabetes, depression and dementia (alone or combined) were collected by searching PubMed and EMBASE. RESULTS The controlling of both neurotransmitters/hormones release and neuronal death could be achieved through modulating Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling). CONCLUSION Taking into account our previous reports on Ca2+/cAMP signalling, and considering a limited discussion in the literature on the role of Ca2+/cAMP signalling in the link between cognitive dysfunctions and brain insulin resistance, this article has comprehensively discussed the role of these signalling pathways in this link (between cognitive dysfunctions and brain insulin resistance).
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Affiliation(s)
- Leandro B Bergantin
- Department of Pharmacology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
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Lu X, Gong W, Wen Z, Hu L, Peng Z, Zha Y. Correlation Between Diabetic Cognitive Impairment and Diabetic Retinopathy in Patients With T2DM by 1H-MRS. Front Neurol 2019; 10:1068. [PMID: 31781013 PMCID: PMC6861416 DOI: 10.3389/fneur.2019.01068] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 09/23/2019] [Indexed: 12/23/2022] Open
Abstract
Objective: To explore the correlation between diabetic cognitive impairment (DCI) and diabetic retinopathy (DR) through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus (T2DM) by 1H-MRS. Methods: Fifty-three patients with T2DM were enrolled for this study. According to the fundus examination, the patients were divided into the DR group (n = 26) and the T2DM without DR group (T2DM group, n = 27). Thirty healthy adults were selected as a control group (HC group, n = 30). Cognitive function was measured by Montreal Cognitive Assessment (MoCA). The peak areas of N-acetylaspartate (NAA), Cho-line (Cho), Creatine (Cr), and Myo-inositol (mI) as well as their ratios were detected by proton magnetic resonance spectroscopy (1H-MRS). The difference analysis between the three groups was performed by one-way ANOVA. When p < 0.05, LSD-t was applied. A partial correlation analysis (with age as a covariate) was used to analyze the correlation between metabolites in the DR group and MoCA scores. Among all T2DM patients, Chi-square test age, gender, education level, BMI, SBP, DBP, FPG, HbA1c, TC, TG, HDL-C, LDL-C, DR, and DCI correlation were measured. Differences were statistically significant while P < 0.05. Results: 1. The scores of MoCA in the DR group or in the T2DM group were significantly less than those in the HC group (F = 3.54, P < 0.05), and the scores of MoCA in the DR group were significantly less than those in the other groups (F = 3.61, P < 0.05). 2. There were significant differences for NAA in the bilateral hippocampus in DR patients, T2DM patients, and healthy controls (P < 0.05). 3. The NAA/Cr was significantly positively correlated with the score of MoCA in DR patients' left hippocampus (r = 0.781, P < 0.01). 4. Chi-square analysis found that there was a correlation between DR and DCI (x2 = 4.6, df = 1, p = 0.032, plt: 0.05). There was no correlation between other influencing factors and DCI (P > 0.05). Conclusion: DCI is closely correlated with the DR in patients with T2DM. Hippocampal brain metabolism may have some changes in two sides of NAA in patients with DR, 1H-MRS may provide effective imaging strategies and methods for the early diagnosis of brain damage and quantitative assessment cognitive function in T2DM.
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Affiliation(s)
- Xuefang Lu
- Department of Radiology, Renmin Hospital, Wuhan, China
| | - Wei Gong
- Department of Radiology, Renmin Hospital, Wuhan, China
| | - Zhi Wen
- Department of Radiology, Renmin Hospital, Wuhan, China
| | - Lanhua Hu
- Department of Radiology, Renmin Hospital, Wuhan, China
| | - Zhoufeng Peng
- Department of Radiology, Renmin Hospital, Wuhan, China
| | - Yunfei Zha
- Department of Radiology, Renmin Hospital, Wuhan, China
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Ebokaiwe AP, Ijomone OM, Osawe SO, Osuji O, Alo M. Influence of Loranthus micranthus against STZ-Induced Neurobehavioral Deficits in Diabetic Rats. NEUROCHEM J+ 2019. [DOI: 10.1134/s1819712419030061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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