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1
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Zhu S, Li H, Xu X, Luo Y, Deng B, Guo X, Guo Y, Yang W, Wei X, Wang Q. The Pathogenesis and Treatment of Cardiovascular Autonomic Dysfunction in Parkinson's Disease: What We Know and Where to Go. Aging Dis 2021; 12:1675-1692. [PMID: 34631214 PMCID: PMC8460297 DOI: 10.14336/ad.2021.0214] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 02/14/2021] [Indexed: 12/15/2022] Open
Abstract
Cardiovascular autonomic dysfunctions (CAD) are prevalent in Parkinson’s disease (PD). It contributes to the development of cognitive dysfunction, falls and even mortality. Significant progress has been achieved in the last decade. However, the underlying mechanisms and effective treatments for CAD have not been established yet. This review aims to help clinicians to better understand the pathogenesis and therapeutic strategies. The literatures about CAD in patients with PD were reviewed. References for this review were identified by searches of PubMed between 1972 and March 2021, with the search term “cardiovascular autonomic dysfunctions, postural hypotension, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension, and nondipping”. The pathogenesis, including the neurogenic and non-neurogenic mechanisms, and the current pharmaceutical and non-pharmaceutical treatment for CAD, were analyzed. CAD mainly includes four aspects, which are OH, SH, postprandial hypotension and nondipping, among them, OH is the main component. Both non-neurogenic and neurogenic mechanisms are involved in CAD. Failure of the baroreflex circulate, which includes the lesions at the afferent, efferent or central components, is an important pathogenesis of CAD. Both non-pharmacological and pharmacological treatment alleviate CAD-related symptoms by acting on the baroreflex reflex circulate. However, pharmacological strategy has the limitation of failing to enhance baroreflex sensitivity and life quality. Novel OH treatment drugs, such as pyridostigmine and atomoxetine, can effectively improve OH-related symptoms via enhancing residual sympathetic tone, without adverse reactions of supine hypertension. Baroreflex impairment is a crucial pathological mechanism associated with CAD in PD. Currently, non-pharmacological strategy was the preferred option for its advantage of enhancing baroreflex sensitivity. Pharmacological treatment is a second-line option. Therefore, to find drugs that can enhance baroreflex sensitivity, especially via acting on its central components, is urgently needed in the scientific research and clinical practice.
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Affiliation(s)
- Shuzhen Zhu
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Hualing Li
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaoyan Xu
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yuqi Luo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Bin Deng
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xingfang Guo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yang Guo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Wucheng Yang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaobo Wei
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qing Wang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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2
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Sleight E, Stringer MS, Marshall I, Wardlaw JM, Thrippleton MJ. Cerebrovascular Reactivity Measurement Using Magnetic Resonance Imaging: A Systematic Review. Front Physiol 2021; 12:643468. [PMID: 33716793 PMCID: PMC7947694 DOI: 10.3389/fphys.2021.643468] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 02/01/2021] [Indexed: 12/27/2022] Open
Abstract
Cerebrovascular reactivity (CVR) magnetic resonance imaging (MRI) probes cerebral haemodynamic changes in response to a vasodilatory stimulus. CVR closely relates to the health of the vasculature and is therefore a key parameter for studying cerebrovascular diseases such as stroke, small vessel disease and dementias. MRI allows in vivo measurement of CVR but several different methods have been presented in the literature, differing in pulse sequence, hardware requirements, stimulus and image processing technique. We systematically reviewed publications measuring CVR using MRI up to June 2020, identifying 235 relevant papers. We summarised the acquisition methods, experimental parameters, hardware and CVR quantification approaches used, clinical populations investigated, and corresponding summary CVR measures. CVR was investigated in many pathologies such as steno-occlusive diseases, dementia and small vessel disease and is generally lower in patients than in healthy controls. Blood oxygen level dependent (BOLD) acquisitions with fixed inspired CO2 gas or end-tidal CO2 forcing stimulus are the most commonly used methods. General linear modelling of the MRI signal with end-tidal CO2 as the regressor is the most frequently used method to compute CVR. Our survey of CVR measurement approaches and applications will help researchers to identify good practice and provide objective information to inform the development of future consensus recommendations.
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Affiliation(s)
- Emilie Sleight
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom,UK Dementia Research Institute, Edinburgh, United Kingdom
| | - Michael S. Stringer
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom,UK Dementia Research Institute, Edinburgh, United Kingdom,*Correspondence: Michael S. Stringer
| | - Ian Marshall
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom,UK Dementia Research Institute, Edinburgh, United Kingdom
| | - Joanna M. Wardlaw
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom,UK Dementia Research Institute, Edinburgh, United Kingdom
| | - Michael J. Thrippleton
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom,UK Dementia Research Institute, Edinburgh, United Kingdom
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3
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Elewa YHA, Ichii O, Nakamura T, Kon Y. Pathological Alternations of Mediastinal Fat-Associated Lymphoid Cluster and Lung in a Streptozotocin-Induced Diabetic Mouse Model. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2021; 27:187-200. [PMID: 33345760 DOI: 10.1017/s1431927620024824] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Diabetes is a devastating global health problem and is considered a predisposing factor for lung injury progression. Furthermore, previous reports of the authors revealed the role of mediastinal fat-associated lymphoid clusters (MFALCs) in advancing respiratory diseases. However, no reports concerning the role of MFALCs on the development of lung injury in diabetes have been published. Therefore, this study aimed to examine the correlations between diabetes and the development of MFALCs and the progression of lung injury in a streptozotocin-induced diabetic mouse model. Furthermore, immunohistochemical analysis for immune cells (CD3+ T-lymphocytes, B220+ B-lymphocytes, Iba1+ macrophages, and Gr1+ granulocytes), vessels markers (CD31+ endothelial cells and LYVE-1+ lymphatic vessels "LVs"), and inflammatory markers (TNF-α and IL-5) was performed. In comparison to the control group, the diabetic group showed lung injury development with a significant increase in MFALC size, immune cells, LVs, and inflammatory marker, and a considerable decrease of CD31+ endothelial cells in both lung and MFALCs was observed. Furthermore, the blood glucose level showed significant positive correlations with MFALCs size, lung injury, immune cells, inflammatory markers, and LYVE-1+ LVs in lungs and MFALCs. Thus, we suggest that the development of MFALCs and LVs could contribute to lung injury progression in diabetic conditions.
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Affiliation(s)
- Yaser H A Elewa
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
- Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan
| | - Osamu Ichii
- Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan
- Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Sapporo, Japan
| | - Teppei Nakamura
- Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan
- Department of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Chitose, Japan
| | - Yasuhiro Kon
- Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita18-Nishi 9, Kita-Ku, Sapporo, Hokkaido060-0818, Japan
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4
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Shibao CA, Biaggioni I. Management of Orthostatic Hypotension, Postprandial Hypotension, and Supine Hypertension. Semin Neurol 2020; 40:515-522. [PMID: 33058087 DOI: 10.1055/s-0040-1713886] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
This review provides recommendations for the treatment of neurogenic orthostatic hypotension (nOH), postprandial hypotension, and supine hypertension. It focuses on novel treatment strategies and new insights into the mechanism underlying these conditions. Our goal is to provide practical advice for clinicians on how to screen, diagnose, and treat these conditions with nonpharmacological and pharmacological approaches. For each disorder, we offered a stepwise recommendation on how to apply these new concepts to successfully ameliorate the symptoms associated with OH to prevent syncope and falls. The management of OH in patients who also have supine hypertension requires special considerations and pharmacotherapy. It is noteworthy that there are few therapeutic options for OH and only two Food and Drug Administration-approved drugs for the treatment of OH and nOH based on randomized clinical trials. We will use these studies to develop evidence-based guidelines for OH. The research is limited for postprandial hypotension and supine hypertension, and therefore the recommendations will be based on small studies, clinical expertise, and, above all, an understanding of the underlying pathophysiology.
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Affiliation(s)
- Cyndya A Shibao
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Italo Biaggioni
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
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5
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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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6
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Kaesmacher J, Kreiser K, Manning NW, Gersing AS, Wunderlich S, Zimmer C, Kleine JF, Wiestler B, Boeckh-Behrens T. Clinical outcome prediction after thrombectomy of proximal middle cerebral artery occlusions by the appearance of lenticulostriate arteries on magnetic resonance angiography: A retrospective analysis. J Cereb Blood Flow Metab 2018; 38:1911-1923. [PMID: 28737109 PMCID: PMC6259316 DOI: 10.1177/0271678x17719790] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Post-ischemic vasodynamic changes in infarcted brain parenchyma are common and range from hypo- to hyperperfusion. In the present study, appearance of the lenticulostriate arteries (LSAs) on postinterventional 3T time-of-flight (TOF)-MRA suggestive for altered post-stroke vasodynamics following thrombectomy was investigated. Patients who underwent thrombectomy for a proximal MCA occlusion and for whom postinterventional 3T TOF-MRA (median at day 3) was available, were included in this retrospective analysis (n=98). LSA appearance was categorized into presence (LSA-sign+) or absence (LSA-sign-) of vasodilatation in the ischemic hemisphere. Functional outcome was determined using the modified Rankin scale (mRS). LSA-sign+ was observed in 64/98 patients. Hypertension (adjusted OR: 0.171, 95% CI: 0.046-0.645) and preinterventional IV rtPA (adjusted OR: 0.265, 95% CI: 0.088-0.798) were associated with absence of the LSA-sign+. In multivariate logistic regression, LSA-sign+ was associated with substantial neurologic improvement (adjusted OR: 10.18, 95% CI: 2.69-38.57) and good functional outcome (discharge-mRS ≤ 2, adjusted OR: 7.127, 95% CI: 1.913-26.551 and day 90 mRS ≤ 2, adjusted OR: 3.786, 95% CI: 1.026-13.973) after correcting for relevant confounders. For all clinical endpoints, model fit improved when including the LSA-sign term (p<0.05). Asymmetrical dilatation of LSAs following successful thrombectomy indicates favorable neurologic and mid-term functional outcomes. This may indicate preserved cerebral blood flow regulatory mechanisms.
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Affiliation(s)
- Johannes Kaesmacher
- 1 Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
| | - Kornelia Kreiser
- 1 Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
| | - Nathan W Manning
- 2 Florey Institute of Neuroscience and Mental Health, University of Melbourne, ViC, Australia
| | - Alexandra S Gersing
- 3 Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Silke Wunderlich
- 4 Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Claus Zimmer
- 1 Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
| | - Justus F Kleine
- 1 Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.,5 Department of Neuroradiology, Vivantes Klinikum Neukölln, Berlin, Germany
| | - Benedikt Wiestler
- 1 Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
| | - Tobias Boeckh-Behrens
- 1 Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
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7
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Zhao X, Han Q, Gang X, Wang G. Altered brain metabolites in patients with diabetes mellitus and related complications - evidence from 1H MRS study. Biosci Rep 2018; 38:BSR20180660. [PMID: 30104398 PMCID: PMC6127672 DOI: 10.1042/bsr20180660] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/23/2018] [Accepted: 08/09/2018] [Indexed: 12/24/2022] Open
Abstract
In recent years, diabetes mellitus (DM) has been acknowledged as an important factor for brain disorders. Significant alterations in brain metabolism have been demonstrated during the development of DM and its complications. Magnetic resonance spectroscopy (MRS), a cutting-edge technique used in biochemical analyses, non-invasively provides insights into altered brain metabolite levels in vivo This review aims to discuss current MRS data describing brain metabolite levels in DM patients with or without complications. Cerebral metabolites including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (mI), glutamate, and glutamine were significantly altered in DM patients, suggesting that energy metabolism, neurotransmission, and lipid membrane metabolism might be disturbed during the progression of DM. Changes in brain metabolites may be non-invasive biomarkers for DM and DM-related complications. Different brain regions presented distinct metabolic signatures, indicating region-specific diabetic brain damages. In addition to serving as biomarkers, MRS data on brain metabolites can also shed light on diabetic treatment monitoring. For example, exercise may restore altered brain metabolite levels and has beneficial effects on cognition in DM patients. Future studies should validate the above findings in larger populations and uncover the mechanisms of DM-induced brain damages.
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Affiliation(s)
- Xue Zhao
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Qing Han
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Xiaokun Gang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
| | - Guixia Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
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8
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Abstract
Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.
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Affiliation(s)
- Cyndya A. Shibao
- Department of Medicine, Division of Clinical Pharmacology, Vanderbilt Autonomic Dysfunction Center, Vanderbilt University Medical Center, Nashville, TN
| | - Horacio Kaufmann
- Department of Neurology, NYU Langone Medical Center, Dysautonomia Center, 530 1st Avenue, New York, NY, USA.
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9
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Jansen JFA, van Bussel FCG, van de Haar HJ, van Osch MJP, Hofman PAM, van Boxtel MPJ, van Oostenbrugge RJ, Schram MT, Stehouwer CDA, Wildberger JE, Backes WH. Cerebral blood flow, blood supply, and cognition in Type 2 Diabetes Mellitus. Sci Rep 2016; 6:10. [PMID: 27920431 PMCID: PMC8276879 DOI: 10.1038/s41598-016-0003-6] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 08/24/2016] [Indexed: 02/06/2023] Open
Abstract
We investigated whether type 2 diabetes (T2DM) and the presence of cognitive impairment are associated with altered cerebral blood flow (CBF). Forty-one participants with and thirty-nine without T2DM underwent 3-Tesla MRI, including a quantitative technique measuring (macrovascular) blood flow in the internal carotid artery and an arterial spin labeling technique measuring (microvascular) perfusion in the grey matter (GM). Three analysis methods were used to quantify the CBF: a region of interest analysis, a voxel-based statistical parametric mapping technique, and a 'distributed deviating voxels' method. Participants with T2DM exhibited significantly more tissue with low CBF values in the cerebral cortex and the subcortical GM (3.8-fold increase). The latter was the only region where the hypoperfusion remained after correcting for atrophy, indicating that the effect of T2DM on CBF, independent of atrophy, is small. Subcortical CBF was associated with depression. No associations were observed for CBF in other regions with diabetes status, for carotid blood flow with diabetes status, or for CBF or flow in relation with cognitive function. To conclude, a novel method that tallies total 'distributed deviating voxels' demonstrates T2DM-associated hypoperfusion in the subcortical GM, not associated with cognitive performance. Whether a vascular mechanism underlies cognitive decrements remains inconclusive.
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Affiliation(s)
- Jacobus F A Jansen
- Departments of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands. .,School for Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands.
| | - Frank C G van Bussel
- Departments of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.,School for Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands
| | - Harm J van de Haar
- Departments of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.,School for Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands.,Departments of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands
| | | | - Paul A M Hofman
- Departments of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Martin P J van Boxtel
- School for Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands.,Departments of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Robert J van Oostenbrugge
- School for Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands.,Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands.,Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Miranda T Schram
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands
| | - Coen D A Stehouwer
- Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands.,Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Joachim E Wildberger
- Departments of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.,Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands
| | - Walter H Backes
- Departments of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.,School for Mental Health and Neuroscience (MHeNS), Maastricht, the Netherlands
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10
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Tabata N, Sueta D, Yamashita T, Utsunomiya D, Arima Y, Yamamoto E, Tsujita K, Kojima S, Kaikita K, Hokimoto S. Relationship between asymptomatic intra-cranial lesions and brachial-ankle pulse wave velocity in coronary artery disease patients without stroke. Hypertens Res 2016; 40:392-398. [PMID: 27881850 DOI: 10.1038/hr.2016.159] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 09/29/2016] [Accepted: 10/12/2016] [Indexed: 12/17/2022]
Abstract
Little is known about the significance of asymptomatic intra-cranial lesions (ICL) identified by brain MRI in coronary artery disease (CAD) patients. Silent cerebral lesions are suggested to be associated with arterial stiffness in healthy subjects. We investigated whether subclinical ICL are associated with arterial stiffness and the prognosis in CAD patients without medical history of cerebrovascular diseases. We recruited CAD patients who required percutaneous coronary intervention (PCI), did not meet exclusion criteria, and agreed with MRI before PCI. Subjects were divided into two groups according to the presence of ICL of cerebral microbleeds or lacunar infarction. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). Clinical outcome was defined as a composite of cardiovascular death, non-fatal myocardial infarction, stroke, unstable angina and heart failure. In total, 149 patients underwent brain MRI. Patients with ICL (n=55) had significantly higher baPWV than those without ICL (1591-2204 vs. 1450-1956 cm per sec; P=0.009). A multivariate analysis showed that male sex (odds ratio (OR), 3.15; 95% confidence interval (CI), 1.38-7.20; P=0.006) and baPWV (OR, 1.001; 95% CI, 1.000-1.002; P=0.023) were predictors of ICL. In total, 12 patients experienced a cardiovascular event. The Kaplan-Meier analysis indicated a significantly higher incidence of cardiovascular events in patients with ICL (log-rank test: P=0.018). Multivariate Cox proportional hazards analyses indicated that ICL finding was a significant predictor of clinical outcome (hazard ratio, 3.41; 95% CI, 1.02-11.5; P=0.047). Patients with subclinical ICL had a higher baPWV and worse prognoses than those without ICL.
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Affiliation(s)
- Noriaki Tabata
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Daisuke Sueta
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takayoshi Yamashita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Daisuke Utsunomiya
- Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuichiro Arima
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Eiichiro Yamamoto
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kenichi Tsujita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Sunao Kojima
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Koichi Kaikita
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Seiji Hokimoto
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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11
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Cerebrovascular reactivity after treatment of unruptured intracranial aneurysms — A transcranial Doppler sonography and acetazolamide study. J Neurol Sci 2016; 363:97-103. [DOI: 10.1016/j.jns.2015.12.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Revised: 12/11/2015] [Accepted: 12/14/2015] [Indexed: 11/19/2022]
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12
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In Vivo NMR Studies of the Brain with Hereditary or Acquired Metabolic Disorders. Neurochem Res 2015; 40:2647-85. [PMID: 26610379 DOI: 10.1007/s11064-015-1772-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2015] [Revised: 11/10/2015] [Accepted: 11/12/2015] [Indexed: 01/09/2023]
Abstract
Metabolic disorders, whether hereditary or acquired, affect the brain, and abnormalities of the brain are related to cellular integrity; particularly in regard to neurons and astrocytes as well as interactions between them. Metabolic disturbances lead to alterations in cellular function as well as microscopic and macroscopic structural changes in the brain with diabetes, the most typical example of metabolic disorders, and a number of hereditary metabolic disorders. Alternatively, cellular dysfunction and degeneration of the brain lead to metabolic disturbances in hereditary neurological disorders with neurodegeneration. Nuclear magnetic resonance (NMR) techniques allow us to assess a range of pathophysiological changes of the brain in vivo. For example, magnetic resonance spectroscopy detects alterations in brain metabolism and energetics. Physiological magnetic resonance imaging (MRI) detects accompanying changes in cerebral blood flow related to neurovascular coupling. Diffusion and T1/T2-weighted MRI detect microscopic and macroscopic changes of the brain structure. This review summarizes current NMR findings of functional, physiological and biochemical alterations within a number of hereditary and acquired metabolic disorders in both animal models and humans. The global view of the impact of these metabolic disorders on the brain may be useful in identifying the unique and/or general patterns of abnormalities in the living brain related to the pathophysiology of the diseases, and identifying future fields of inquiry.
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13
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Barsanti C, Lenzarini F, Kusmic C. Diagnostic and prognostic utility of non-invasive imaging in diabetes management. World J Diabetes 2015; 6:792-806. [PMID: 26131322 PMCID: PMC4478576 DOI: 10.4239/wjd.v6.i6.792] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 12/23/2014] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed.
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CAO ZHEN, YE BIDI, SHEN ZHIWEI, CHENG XIAOFANG, YANG ZHONGXIAN, LIU YANYAN, WU RENHUA, GENG KUAN, XIAO YEYU. 2D-1H proton magnetic resonance spectroscopic imaging study on brain metabolite alterations in patients with diabetic hypertension. Mol Med Rep 2015; 11:4232-8. [PMID: 25652580 PMCID: PMC4394930 DOI: 10.3892/mmr.2015.3305] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 01/09/2015] [Indexed: 02/05/2023] Open
Abstract
The aim of the present study was to investigate the possible metabolic alterations in the frontal cortex and parietal white matter in patients with diabetic hypertension (DHT) using proton magnetic resonance (MR) spectroscopic imaging. A total of 33 DHT patients and 30 healthy control subjects aged between 45 and 75 were included in the present study. All subjects were right‑handed. The spectroscopy data were collected using a GE Healthcare 1.5T MR scanner. The multi‑voxels were located in the semioval center (repetition time/echo time=1,500 ms/35 ms). The area of interest was 8x10x2 cm in volume and contained the two sides of the frontal cortex and the parietal white matter. The spectra data were processed using SAGE software. The ratios of brain metabolite concentrations, particularly for N‑acetylaspartate (NAA)/creatine (Cr) and Choline (Cho)/Cr were calculated and analyzed. Statistical analyses were performed using SPSS 17.0. The NAA/Cr ratio of the bilateral prefrontal cortex of the DHT group was significantly lower than that of the control group (left t=‑7.854, P=0.000 and right t=‑5.787, P=0.000), The Cho/Cr ratio was also much lower than the control group (left t=2.422, P=0.024 and right t=2.920, P=0.007). NAA/Cr ratio of the left parietal white matter of the DHT group was extremely lower than that of the control group (t=‑4.199, P=0.000). Therefore, DHT may result in metabolic disorders in the frontal cortex and parietal white matter but the metabolic alterations are different in various regions of the brain. The alteration in cerebral metabolism is associated with diabetes and hypertension. The ratios of NAA/Cr and Cho/Cr are potential metabolic markers for the brain damage induced by DHT.
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Affiliation(s)
- ZHEN CAO
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - BI-DI YE
- Department of Medical Imaging, The Central Hospital of Huizhou City, Huizhou, Guangdong 516001, P.R. China
| | - ZHI-WEI SHEN
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - XIAO-FANG CHENG
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - ZHONG-XIAN YANG
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - YAN-YAN LIU
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - REN-HUA WU
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
- Correspondence to: Dr Ren-Hua Wu or Dr Ye-Yu Xiao, Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, 69 Dongxiabei Road, Shantou, Guangdong 515041, P.R. China, E mail: , E mail:
| | - KUAN GENG
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
| | - YE-YU XIAO
- Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
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Auer MK, Sack M, Lenz JN, Jakovcevski M, Biedermann SV, Falfán-Melgoza C, Deussing J, Steinle J, Bielohuby M, Bidlingmaier M, Pfister F, Stalla GK, Ende G, Weber-Fahr W, Fuss J, Gass P. Effects of a high-caloric diet and physical exercise on brain metabolite levels: a combined proton MRS and histologic study. J Cereb Blood Flow Metab 2015; 35:554-64. [PMID: 25564238 PMCID: PMC4420876 DOI: 10.1038/jcbfm.2014.231] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Revised: 11/17/2014] [Accepted: 11/25/2014] [Indexed: 11/09/2022]
Abstract
Excessive intake of high-caloric diets as well as subsequent development of obesity and diabetes mellitus may exert a wide range of unfavorable effects on the central nervous system (CNS). It has been suggested that one mechanism in this context is the promotion of neuroinflammation. The potentially harmful effects of such diets were suggested to be mitigated by physical exercise. Here, we conducted a study investigating the effects of physical exercise in a cafeteria-diet mouse model on CNS metabolites by means of in vivo proton magnetic resonance spectroscopy ((1)HMRS). In addition postmortem histologic and real-time (RT)-PCR analyses for inflammatory markers were performed. Cafeteria diet induced obesity and hyperglycemia, which was only partially moderated by exercise. It also induced several changes in CNS metabolites such as reduced hippocampal glutamate (Glu), choline-containing compounds (tCho) and N-acetylaspartate (NAA)+N-acetyl-aspartyl-glutamic acid (NAAG) (tNAA) levels, whereas opposite effects were seen for running. No association of these effects with markers of central inflammation could be observed. These findings suggest that while voluntary wheel running alone is insufficient to prevent the unfavorable peripheral sequelae of the diet, it counteracted many changes in brain metabolites. The observed effects seem to be independent of neuroinflammation.
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Affiliation(s)
- Matthias K Auer
- 1] RG Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany [2] RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Markus Sack
- 1] RG Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany [2] Department of Neuroimaging, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Jenny N Lenz
- 1] RG Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany [2] RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Mira Jakovcevski
- RG Molecular Neurogenetics, Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany
| | - Sarah V Biedermann
- Department of Neuroimaging, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Claudia Falfán-Melgoza
- 1] RG Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany [2] Department of Neuroimaging, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Jan Deussing
- RG Molecular Neurogenetics, Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany
| | - Jörg Steinle
- RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Maximilian Bielohuby
- Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians University, Munich, Germany
| | - Martin Bidlingmaier
- Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians University, Munich, Germany
| | - Frederik Pfister
- Department of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Günter K Stalla
- RG Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
| | - Gabriele Ende
- Department of Neuroimaging, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Wolfgang Weber-Fahr
- 1] RG Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany [2] Department of Neuroimaging, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Johannes Fuss
- RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
| | - Peter Gass
- RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
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Hajek T, Calkin C, Blagdon R, Slaney C, Alda M. Type 2 diabetes mellitus: a potentially modifiable risk factor for neurochemical brain changes in bipolar disorders. Biol Psychiatry 2015; 77:295-303. [PMID: 24331546 DOI: 10.1016/j.biopsych.2013.11.007] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Revised: 11/08/2013] [Accepted: 11/08/2013] [Indexed: 11/16/2022]
Abstract
BACKGROUND Neuroimaging changes in bipolar disorder (BD) may be secondary to the presence of certain clinical factors. Type 2 diabetes mellitus (T2DM) damages the brain and frequently co-occurs with BD. Studying patients with both T2DM and BD could help identify preventable risk factors for neuroimaging changes in BD. METHODS We used 1.5T magnetic resonance spectroscopy to measure prefrontal N-acetylaspartate (NAA), which is mainly localized in neurons, and total creatine (tCr), an energy metabolite, in 19 BD patients with insulin resistance/glucose intolerance (BD + IR/GI), 14 BD subjects with T2DM (BD + T2DM), 15 euglycemic BD participants, and 11 euglycemic, nonpsychiatric control. RESULTS The levels of NAA and tCr were lowest among BD + T2DM, intermediate in the BD + IR/GI, and highest among the euglycemic BD and control subjects (F₃,₅₅ = 4.57, p = .006; F₃,₅₅ = 2.92, p = .04, respectively). Even the BD + IR/GI subjects had lower NAA than the euglycemic participants (t₄₃ = 2.13, p = .04). Total Cr was associated with NAA (β = .52, t₅₆ = 5.57, p = .000001). Both NAA and tCr correlated with Global Assessment of Functioning scores (r₄₆ = .28, p = .05; r₄₆ = .48, p = .0004, respectively). CONCLUSIONS T2DM, but also prediabetes, may be risk factors for prefrontal neurochemical alterations in BD. These changes were associated with poor psychosocial functioning and could indicate impaired energy metabolism. The findings emphasize the importance of improving diabetes care in BD and suggest potential options for treatment of neuroimaging alterations.
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Affiliation(s)
- Tomas Hajek
- Department of Psychiatry (TH, CC, RB, CS, MA), Dalhousie University, Halifax, Nova Scotia, Canada; Prague Psychiatric Center (TH, MA), Department of Psychiatry and Medical Psychology, 3rd School of Medicine, Charles University, Prague, Czech Republic.
| | - Cynthia Calkin
- Department of Psychiatry (TH, CC, RB, CS, MA), Dalhousie University, Halifax, Nova Scotia, Canada
| | - Ryan Blagdon
- Department of Psychiatry (TH, CC, RB, CS, MA), Dalhousie University, Halifax, Nova Scotia, Canada
| | - Claire Slaney
- Department of Psychiatry (TH, CC, RB, CS, MA), Dalhousie University, Halifax, Nova Scotia, Canada
| | - Martin Alda
- Department of Psychiatry (TH, CC, RB, CS, MA), Dalhousie University, Halifax, Nova Scotia, Canada; Prague Psychiatric Center (TH, MA), Department of Psychiatry and Medical Psychology, 3rd School of Medicine, Charles University, Prague, Czech Republic
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Brundel M, Kappelle LJ, Biessels GJ. Brain imaging in type 2 diabetes. Eur Neuropsychopharmacol 2014; 24:1967-81. [PMID: 24726582 DOI: 10.1016/j.euroneuro.2014.01.023] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Accepted: 01/23/2014] [Indexed: 02/08/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and dementia. Brain imaging may provide important clues about underlying processes. This review focuses on the relationship between T2DM and brain abnormalities assessed with different imaging techniques: both structural and functional magnetic resonance imaging (MRI), including diffusion tensor imaging and magnetic resonance spectroscopy, as well as positron emission tomography and single-photon emission computed tomography. Compared to people without diabetes, people with T2DM show slightly more global brain atrophy, which increases gradually over time compared with normal aging. Moreover, vascular lesions are seen more often, particularly lacunar infarcts. The association between T2DM and white matter hyperintensities and microbleeds is less clear. T2DM has been related to diminished cerebral blood flow and cerebrovascular reactivity, particularly in more advanced disease. Diffusion tensor imaging is a promising technique with respect to subtle white matter involvement. Thus, brain imaging studies show that T2DM is associated with both degenerative and vascular brain damage, which develops slowly over the course of many years. The challenge for future studies will be to further unravel the etiology of brain damage in T2DM, and to identify subgroups of patients that will develop distinct progressive brain damage and cognitive decline.
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Affiliation(s)
- Manon Brundel
- Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
| | - L Jaap Kappelle
- Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands
| | - Geert Jan Biessels
- Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands
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18
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Lee JH, Choi Y, Jun C, Hong YS, Cho HB, Kim JE, Lyoo IK. Neurocognitive changes and their neural correlates in patients with type 2 diabetes mellitus. Endocrinol Metab (Seoul) 2014; 29:112-21. [PMID: 25031883 PMCID: PMC4091490 DOI: 10.3803/enm.2014.29.2.112] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
As the prevalence and life expectancy of type 2 diabetes mellitus (T2DM) continue to increase, the importance of effective detection and intervention for the complications of T2DM, especially neurocognitive complications including cognitive dysfunction and dementia, is receiving greater attention. T2DM is thought to influence cognitive function through an as yet unclear mechanism that involves multiple factors such as hyperglycemia, hypoglycemia, and vascular disease. Recent developments in neuroimaging methods have led to the identification of potential neural correlates of T2DM-related neurocognitive changes, which extend from structural to functional and metabolite alterations in the brain. The evidence indicates various changes in the T2DM brain, including global and regional atrophy, white matter hyperintensity, altered functional connectivity, and changes in neurometabolite levels. Continued neuroimaging research is expected to further elucidate the underpinnings of cognitive decline in T2DM and allow better diagnosis and treatment of the condition.
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Affiliation(s)
- Junghyun H Lee
- College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
- Ewha Brain Institute, Ewha Womans University, Seoul, Korea
| | - Yera Choi
- Ewha Brain Institute, Ewha Womans University, Seoul, Korea
- Interdisciplinary Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea
| | - Chansoo Jun
- College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
- Ewha Brain Institute, Ewha Womans University, Seoul, Korea
| | - Young Sun Hong
- Ewha Brain Institute, Ewha Womans University, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Han Byul Cho
- Ewha Brain Institute, Ewha Womans University, Seoul, Korea
- Interdisciplinary Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea
| | - Jieun E Kim
- Ewha Brain Institute, Ewha Womans University, Seoul, Korea
- Department of Brain and Cognitive Sciences, Ewha Womans University Graduate School, Seoul, Korea
| | - In Kyoon Lyoo
- College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
- Ewha Brain Institute, Ewha Womans University, Seoul, Korea
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19
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Bal S, Goyal M, Smith E, Demchuk AM. Central nervous system imaging in diabetic cerebrovascular diseases and white matter hyperintensities. HANDBOOK OF CLINICAL NEUROLOGY 2014; 126:291-315. [PMID: 25410230 DOI: 10.1016/b978-0-444-53480-4.00021-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Diabetes mellitus is an important vascular risk factor for cerebrovascular disease. This occurs through pathophysiologic changes to the microcirculation as arteriolosclerosis and to the macrocirculation as large artery atherosclerosis. Imaging techniques can provide detailed visualization of the cerebrovasculature using CT (computed tomography) angiography and MR (magnetic resonance) angiography. Newer techniques focused on advanced parenchymal imaging include CT perfusion, quantitative MRI, and diffusion tensor imaging; each identifies brain lesion burden due to diabetes mellitus. These imaging approaches have provided insights into the diabetes mellitus brain and cerebral circulation pathophysiology. Imaging has taught us that diabetics develop cerebral atrophy, silent infarcts, and white matter disease more rapidly than other patient populations. Longitudinal studies are needed to quantify the rate and extent of such structural brain and blood vessel changes and how they relate to cognitive decline. Diabetes prevention and treatment strategies will then be possible to slow the development of such changes.
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Affiliation(s)
- Simerpreet Bal
- Department of Clinical Neurosciences and Radiology, Foothills Medical Centre, Calgary, Alberta, Canada
| | - Mayank Goyal
- Department of Clinical Neurosciences and Radiology, Foothills Medical Centre, Calgary, Alberta, Canada
| | - Eric Smith
- Department of Clinical Neurosciences and Radiology, Foothills Medical Centre, Calgary, Alberta, Canada
| | - Andrew M Demchuk
- Department of Clinical Neurosciences and Radiology, Foothills Medical Centre, Calgary, Alberta, Canada.
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20
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Lin Y, Zhou J, Sha L, Li Y, Qu X, Liu L, Chen H, An Z, Wang Y, Sun C. Metabolite differences in the lenticular nucleus in type 2 diabetes mellitus shown by proton MR spectroscopy. AJNR Am J Neuroradiol 2013; 34:1692-6. [PMID: 23598834 DOI: 10.3174/ajnr.a3492] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND AND PURPOSE Previous studies by using proton MR spectroscopy found metabolite abnormalities in the cerebral cortex and white matter of patients with type 2 diabetes mellitus. The present study was undertaken to detect metabolite differences in the lenticular nuclei and thalamus in patients with T2DM. MATERIALS AND METHODS Twenty subjects with T2DM and 22 age-matched control subjects underwent single-voxel MR spectroscopy in the left and right lenticular nuclei and left and right thalami. NAA/Cr and Cho/Cr ratios were calculated. Brain lactic acid, fasting blood glucose, and glycosylated hemoglobin levels were also monitored. RESULTS The NAA/Cr ratio was lower in the left lenticular nuclei of subjects with T2DM (P = .007), whereas the Cho/Cr ratio was increased in both the and right lenticular nuclei (P = .001). The NAA/Cr ratio was negatively correlated with FBG in the left (r = -0.573, P = .008) and right nuclei (r = -0.564, P = .010). It was also negatively correlated to HbA1c in the left (r = -0.560, P = .010) and right (r = -0.453, P = .045) nuclei. The Cho/Cr ratio was positively correlated with these variables (P < .05). No significant differences in NAA/Cr or Cho/Cr ratios were observed in the thalamus of patients with T2DM. Lactic acid was not detected in any of the patients in the study. CONCLUSIONS The different metabolic statuses of the lenticular nuclei and thalamus suggest different effects of T2DM in each of these brain nuclei, with the lenticular nuclei being more vulnerable than the thalamus. The abnormal metabolic status was observed before lesions had appeared in these brain areas.
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Leung J, Behpour A, Sokol N, Mohanta A, Kassner A. Assessment of intracranial blood flow velocities using a computer controlled vasoactive stimulus: A comparison between phase contrast magnetic resonance angiography and transcranial doppler ultrasonography. J Magn Reson Imaging 2012; 38:733-8. [DOI: 10.1002/jmri.23911] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Accepted: 09/25/2012] [Indexed: 11/11/2022] Open
Affiliation(s)
- Jackie Leung
- Department of Physiology and Experimental Medicine; Hospital for Sick Children Toronto; Ontario; Canada
| | | | - Neil Sokol
- Department of Medical Imaging; University of Toronto; Toronto, Ontario; Canada
| | - Arun Mohanta
- Diagnostic Imaging, Hospital for Sick Children; Toronto, Ontario; Canada
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Abstract
The relationship between cerebral hemodynamics and cognitive performance has increasingly become recognized as a major challenge in clinical practice for older adults. Both diabetes and hypertension worsen brain perfusion and are major risk factors for cerebrovascular disease, stroke and dementia. Cerebrovascular reserve has emerged as a potential biomarker for monitoring pressure-perfusion-cognition relationships. Endothelial dysfunction and inflammation, microvascular disease, and mascrovascular disease affect cerebral hemodynamics and play an important role in pathohysiology and severity of multiple medical conditions, presenting as cognitive decline in the old age. Therefore, the identification of cerebrovascular vascular reactivity as a new therapeutic target is needed for prevention of cognitive decline late in life.
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Cardoso S, Santos RX, Correia SC, Carvalho C, Santos MS, Baldeiras I, Oliveira CR, Moreira PI. Insulin-induced recurrent hypoglycemia exacerbates diabetic brain mitochondrial dysfunction and oxidative imbalance. Neurobiol Dis 2012; 49:1-12. [PMID: 22940631 DOI: 10.1016/j.nbd.2012.08.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Revised: 07/21/2012] [Accepted: 08/16/2012] [Indexed: 12/17/2022] Open
Abstract
Intensive insulin therapy can prevent or slow the progression of long-term diabetes complications but, at the same time, it increases the risk for episodes of severe hypoglycemia. In our study, we used a protocol intended to mimic the levels of blood glucose that occur in type 1 diabetic patients under an intensive insulin therapy. Streptozotocin (STZ)-induced diabetic rats were treated subcutaneously with twice-daily insulin injections for 2weeks to induce hypoglycemic episodes. Brain cortical and hippocampal mitochondria were isolated and mitochondrial bioenergetics (respiratory chain and phosphorylation system) and oxidative status parameters (malondialdehyde (MDA) levels, mitochondrial aconitase activity and enzymatic and non-enzymatic antioxidant defenses) were analyzed. The protein levels of synaptophysin, a marker of synaptic integrity, and caspase 9 activity were also evaluated in cortical and hippocampal homogenates. Brain cortical mitochondria isolated from hyper- and recurrent hypoglycemic animals presented higher levels of MDA and α-tocopherol together with an increased glutathione disulfide reductase activity, lower manganese superoxide dismutase (MnSOD) activity and glutathione-to-glutathione disulfide (GSH/GSSG) ratio. No significant alterations were found in cortical mitochondrial respiratory chain and oxidative phosphorylation system. Hippocampal mitochondria from both experimental groups presented an impaired oxidative phosphorylation system characterized by a decreased mitochondrial energization potential and ATP levels and higher repolarization lag phase. In addition, higher MDA levels and decreased GSH/GSSG, α-tocopherol levels, and aconitase, glutathione peroxidase and MnSOD activities were observed in both groups of animals. Hippocampal mitochondria from recurrent hypoglycemic animals also showed an impairment of the respiratory chain characterized by a lower state 3 of respiration, respiratory control ratio and ADP/O index, and a higher state 4 of respiration. Additionally, a non-statistically significant decrease in synaptophysin protein levels was observed in cortical homogenates from recurrent hypoglycemic rats as well as in hippocampal homogenates from hyperglycemic and recurrent hypoglycemic rats. An increase in caspase 9 activity was also observed in hippocampal homogenates from hyperglycemic and recurrent hypoglycemic animals. Our results show that mitochondrial dysfunction induced by long-term hyperglycemic effects is exacerbated by recurrent hypoglycemia, which may compromise the function and integrity of brain cells.
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Affiliation(s)
- Susana Cardoso
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal
| | - Renato X Santos
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal
| | - Sónia C Correia
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal
| | - Cristina Carvalho
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal
| | - Maria S Santos
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal
| | - Inês Baldeiras
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Laboratory of Neurochemistry, Coimbra University Hospital, Portugal; Neurology Department, Faculty of Medicine, University of Coimbra, Portugal
| | - Catarina R Oliveira
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Portugal
| | - Paula I Moreira
- Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal.
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Chen AY, Ha JN, Delano FA, Schmid-Schönbein GW. Receptor cleavage and P-selectin-dependent reduction of leukocyte adhesion in the spontaneously hypertensive rat. J Leukoc Biol 2012; 92:183-94. [PMID: 22566571 DOI: 10.1189/jlb.0112010] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
The SHR, a genetic model for hypertension and the metabolic syndrome, has attenuated leukocyte adhesion to the postcapillary endothelium by an unknown mechanism. Based on recent evidence of elevated levels of MMPs in plasma and on microvascular endothelium of the SHR with cleavage of several receptor types, we hypothesize that the reduced leukocyte-endothelial interaction is a result of enhanced proteolytic cleavage of P-selectin on the postcapillary endothelium and PSGL-1 on leukocytes. The attenuated rolling interactions of SHR leukocytes with the endothelium were restored by chronic treatment with a broad-spectrum MMP inhibitor (CGS) for 24 weeks. The SHR MMP levels, in plasma and mesentery, as well as the systolic blood pressure, decreased significantly with treatment. In the SHR mesentery, labeling of P-selectin in the postcapillary venules by immunohistochemistry demonstrated, on average, a 31% lower extracellular P-selectin density compared with the normotensive WKY. A significantly lower extracellular PSGL-1 density on the membranes of SHR neutrophils compared with the WKY also supported our hypothesis. In vivo stimulation of the mesenteric postcapillary venules with histamine demonstrated that the SHR had an attenuated response, as measured by leukocyte rolling velocity on the endothelium. The reduced P-selectin and PSGL-1 density, on SHR postcapillary endothelium and on SHR leukocytes, respectively, was restored significantly by chronic MMP inhibition. The impaired ability of SHR leukocytes to reduce rolling velocity upon inflammatory stimulation led to fewer firmly adhered leukocytes to the endothelium as a contributor to immune suppression.
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Affiliation(s)
- Angela Y Chen
- Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093-0412, USA.
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Kuwashiro T, Kamouchi M, Ago T, Hata J, Sugimori H, Kitazono T. The factors associated with a functional outcome after ischemic stroke in diabetic patients: The Fukuoka Stroke Registry. J Neurol Sci 2012; 313:110-4. [DOI: 10.1016/j.jns.2011.09.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Revised: 09/12/2011] [Accepted: 09/13/2011] [Indexed: 01/04/2023]
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Abstract
The relationship between blood pressure (BP) and cognitive outcomes in elderly adults has implications for global health care. Both hypertension and hypotension affect brain perfusion and worsen cognitive outcomes. The presence of hypertension and other vascular risk factors has been associated with decreased performance in executive function and attention tests. Cerebrovascular reserve has emerged as a potential biomarker for monitoring pressure-perfusion-cognition relationships. A decline in vascular reserve capacity can lead to impaired neurovascular coupling and decreased cognitive ability. Endothelial dysfunction, microvascular disease, and mascrovascular disease in midlife could also have an important role in the manifestations and severity of multiple medical conditions underlying cognitive decline late in life. However, questions remain about the role of antihypertensive therapies for long-term prevention of cognitive decline. In this Review, we address the underlying pathophysiology and the existing evidence supporting the role of vascular factors in late-life cognitive decline.
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Affiliation(s)
- Vera Novak
- Division of Gerontology, Beth Israel Deaconess Medical Center and Harvard Medical School, 110 Francis Street, LMOB Suite 1b, Boston, MA 02215, USA.
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Heikkilä O, Mäkimattila S, Timonen M, Groop PH, Heikkinen S, Lundbom N. Cerebellar Glucose During Fasting and Acute Hyperglycemia in Nondiabetic Men and in Men with Type 1 Diabetes. THE CEREBELLUM 2010; 9:336-44. [DOI: 10.1007/s12311-010-0166-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Abstract
Although hypertension is well known as a cause of vascular dementia (VaD), recent findings highlight the role of hypertension in the pathogenesis of Alzheimer's disease (AD) as well as mild cognitive impairment (MCI). Recent studies have shown that disruption of diurnal blood pressure (BP) variation is closely associated with cognitive impairment via injury of the small cerebral arteries indicating that long-standing hypertension constitutes a risk of brain matter atrophy or white matter lesions (WMLs). In several clinical trials, BP-lowering with antihypertensive agents was suggested to reduce the risk of dementia or cognitive decline. This review paper focuses on the role of hypertension as a risk factor for cognitive impairment, and summarizes current knowledge on the relationships between ambulatory BP monitoring (ABPM) and cognitive impairment. Finally, an overview of the impact of antihypertensive therapy on dementia prevention is provided.
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Abstract
The renin-angiotensin system (RAS) is involved in pathological mechanisms of target organ damage as well as the induction of hypertension; therefore, blockade of the RAS has been expected to prevent cardiovascular and cerebrovascular diseases beyond its antihypertensive effects. In spite of the well-characterized role of angiotensin (Ang) II receptor blockers (ARBs) in preventing the onset and recurrence of stroke, the clinical evidence for an effect of ARBs on dementia has not been definitive. However, preliminary experiments raise the possibility that treatment using ARBs may prevent ischemic brain damage and cognitive impairment. Moreover, recent reports have shown that some ARBs prevent amyloid beta deposition in the brain and attenuate cognitive impairment in Alzheimer disease models. Furthermore, recent cohort studies indicate that lower incidence of Alzheimer disease is observed in elderly individuals treated with ARBs. These results indicate a beneficial role for ARBs in cognitive impairment associated with vascular disease, Alzheimer disease, metabolic syndrome and other neurodegenerative diseases. Here, we review the effects of ARBs on the brain with a focus on dementia and future therapeutic approaches for elderly people suffering from disabilities.
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Affiliation(s)
- Masaki Mogi
- Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Ehime, Japan.
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Hajjar I, Hart M, Milberg W, Novak V, Lipsitz L. The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: role of the renin angiotensin system inhibition. BMC Geriatr 2009; 9:48. [PMID: 19922631 PMCID: PMC2784465 DOI: 10.1186/1471-2318-9-48] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2009] [Accepted: 11/18/2009] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC), to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide) in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments. METHODS/DESIGN The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older) with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control") for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP < 140 mm Hg and DBP < 90 mm Hg. Additional antihypertensives are added to achieve this goal if needed. Eligible participants are those with hypertension, defined as a blood pressure 140/90 mm Hg or greater, early cognitive impairment without dementia defined (10 or less out of 15 on the executive clock draw test or 1 standard deviation below the mean on the immediate memory subtest of the repeatable battery for the assessment of neuropsychological status and Mini-Mental-Status-exam >20 and without clinical diagnosis of dementia or Alzheimer's disease). Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives), 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory), cerebral blood flow, and carbon dioxide cerebral vasoreactivity. DISCUSSION The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the threshold of dementia. Success of this trial will offer new therapeutic application of antihypertensives that inhibit the renin angiotensin system and new insights in the role of this system in aging. TRIAL REGISTRATION Clinicaltrials.gov NCT00605072.
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Tiehuis A, van der Meer F, Mali W, Pleizier M, Biessels GJ, Kappelle J, Luijten P. MR spectroscopy of cerebral white matter in type 2 diabetes; no association with clinical variables and cognitive performance. Neuroradiology 2009; 52:155-61. [DOI: 10.1007/s00234-009-0598-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2009] [Accepted: 09/09/2009] [Indexed: 10/20/2022]
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Sander D, Kearney MT. Reducing the risk of stroke in type 2 diabetes: pathophysiological and therapeutic perspectives. J Neurol 2009; 256:1603-19. [PMID: 19399381 DOI: 10.1007/s00415-009-5143-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2009] [Revised: 04/06/2009] [Accepted: 04/15/2009] [Indexed: 12/18/2022]
Abstract
Reducing the excess cerebrovascular burden in patients with type 2 diabetes remains a major therapeutic challenge, especially with respect to the high risk of recurrent events. Targeting the traditional metabolic risk factors of hypertension, dyslipidemia, and hyperglycemia has failed to remove this excess risk, and agents targeting thrombotic risk (i.e., antiplatelet and anticoagulant drugs) remain poorly studied in the context of stroke in diabetes. This may relate to the accumulation of risk factors in type 2 diabetes as well as to diabetes-specific pathophysiologic factors. Regrettably, there is a lack of prospective evidence to support the efficacy of interventions in the secondary prevention of cerebrovascular events in type 2 diabetes, particularly recurrent stroke events. Overall, there is a need for rigorous evaluations of new therapeutic approaches in both primary and secondary prevention of stroke and management of acute stroke in patients with type 2 diabetes. This systematic review of the published literature summarizes the evidence regarding current therapeutic interventions and their impact on the risk of stroke in people with type 2 diabetes, and highlights potential strategies for improving outcomes.
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Affiliation(s)
- Dirk Sander
- Department of Neurology, Medical Park Hospital, Thanngasse 15, 83483 Bischofswiesen, Germany.
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Claassen JAHR, Levine BD, Zhang R. Cerebral vasomotor reactivity before and after blood pressure reduction in hypertensive patients. Am J Hypertens 2009; 22:384-91. [PMID: 19229191 DOI: 10.1038/ajh.2009.2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hypertension is associated with cerebrovascular remodeling and endothelial dysfunction, which may reduce cerebral vasomotor reactivity to CO2. Treatment combining blood pressure (BP) reduction with inhibition of vascular effects of angiotensin II may reverse these changes. However, the reduction in BP at the onset of treatment can compromise cerebral perfusion and exhaust vasomotor reserve, leading to impaired CO2 reactivity. METHODS Eleven patients (nine men, two women) with newly diagnosed, untreated mild-to-moderate hypertension aged (mean (s.d.)) 52 (9) years, and eight controls (seven men, one woman) aged 46 (10) years were studied. Patients received losartan/hydrochlorothiazide (50/12.5 or 100/25 mg) to reduce BP to <140/<90 mm Hg within 1-2 weeks. BP (Finapres), heart rate (HR), CBFV (cerebral blood flow velocity, transcranial Doppler), cerebrovascular resistance, and CO2 reactivity were measured at baseline, after the rapid BP reduction, and after long-term treatment (3-4 months). RESULTS At baseline, hypertension was not associated with reduced CO2 reactivity. Treatment effectively lowered BP from 148 (12)/89 (7) to 130 (15)/80 (9) after 1-2 weeks and 125 (10)/77 (7) mm Hg after 3-4 months (P = 0.003). CO2 reactivity was not affected by the reduction in BP within 2 weeks, and long-term treatment did not augment reactivity. CONCLUSIONS In hypertension without diabetes or advanced cerebrovascular disease, CO2 reactivity is not reduced, and rapid normalization (within 2 weeks) of BP does not exhaust vasomotor reserve. CO2 reactivity did not change between 2 and 12 weeks of treatment, which argues against a direct vascular effect of angiotensin II inhibition within this period.
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Ochi N, Tabara Y, Igase M, Nagai T, Kido T, Miki T, Kohara K. Silent cerebral microbleeds associated with arterial stiffness in an apparently healthy subject. Hypertens Res 2009; 32:255-60. [PMID: 19262493 DOI: 10.1038/hr.2009.13] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Silent cerebral microbleeds (MBs) are a common finding in stroke patients, especially those with intracerebral hemorrhage, and are thought to be a marker of future cerebral hemorrhage. Clinically, two distinct forms of MBs have been documented, those observed with either or both stroke or small vessel disease (SVD) and those associated with cerebral amyloid angiopathy. We investigated a possible association between MBs and arterial stiffness in a general population. Subjects were 443 apparently healthy individuals with a mean age of 67.1+/-8.1 years. The presence of MBs, lacunar infarcts and periventricular hyperintensity (PVH) was determined by 3-tesla magnetic resonance imaging. Carotid intima-media thickness (IMT) was measured by ultrasonography. Arterial stiffness was evaluated by brachial-to-ankle pulse wave velocity (baPWV), and the Framingham stroke risk score (FSRS) was obtained as an integrated cerebrovascular risk factor. The prevalence of MBs was 5.0%. Both baPWV and FSRS were significantly higher in subjects with MBs (1820+/-308 vs. 1645+/-325 cm/s, P=0.014 and 12.1+/-8.6 vs. 8.9+/-7.5%, P=0.047, respectively). Odds ratio of a high baPWV, defined as >or=1500 cm/s, for the presence of MBs was 6.05 even after correction for confounding parameters, including age and hypertension. This association with high baPWV remained irrespective of MBs location, whether strictly located in the lobes or in the basal ganglia and infratentorial regions. These findings indicate an association between arterial stiffness and the presence of MBs. Assessment of arterial stiffness may be useful in identifying subjects at high risk for the presence of MBs.
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Affiliation(s)
- Namiko Ochi
- Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan
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Lao Z, Shen D, Liu D, Jawad AF, Melhem ER, Launer LJ, Bryan RN, Davatzikos C. Computer-assisted segmentation of white matter lesions in 3D MR images using support vector machine. Acad Radiol 2008; 15:300-13. [PMID: 18280928 PMCID: PMC2528894 DOI: 10.1016/j.acra.2007.10.012] [Citation(s) in RCA: 187] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2007] [Revised: 09/29/2007] [Accepted: 10/01/2007] [Indexed: 11/29/2022]
Abstract
RATIONALE AND OBJECTIVES Brain lesions, especially white matter lesions (WMLs), are associated with cardiac and vascular disease, but also with normal aging. Quantitative analysis of WML in large clinical trials is becoming more and more important. MATERIALS AND METHODS In this article, we present a computer-assisted WML segmentation method, based on local features extracted from multiparametric magnetic resonance imaging (MRI) sequences (ie, T1-weighted, T2-weighted, proton density-weighted, and fluid attenuation inversion recovery MRI scans). A support vector machine classifier is first trained on expert-defined WMLs, and is then used to classify new scans. RESULTS Postprocessing analysis further reduces false positives by using anatomic knowledge and measures of distance from the training set. CONCLUSIONS Cross-validation on a population of 35 patients from three different imaging sites with WMLs of varying sizes, shapes, and locations tests the robustness and accuracy of the proposed segmentation method, compared with the manual segmentation results from two experienced neuroradiologists.
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Affiliation(s)
- Zhiqiang Lao
- Department of Radiology, 3600 Market Street, Suite 380, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Shah IM, Ghosh SK, Collier A. Stroke presentation in Type 2 diabetes and the metabolic syndrome. Diabetes Res Clin Pract 2008; 79:e1-4. [PMID: 17707541 DOI: 10.1016/j.diabres.2007.07.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2007] [Accepted: 07/03/2007] [Indexed: 01/22/2023]
Abstract
INTRODUCTION The metabolic syndrome (MetS) is associated with macrovascular disease and an altered pattern of cerebrovascular disease. We investigated stroke subtype presentation in Type 2 diabetic (T2D) patients, and analysed patients with and without the MetS. METHODS We performed a retrospective analysis of 243 T2D patients with first presentation of stroke from our Diabetes Centre database. The MetS was diagnosed in patients with T2D and two or more additional risk factors (obesity, low HDL cholesterol, elevated triglycerides or hypertension). We analysed the clinical stroke subtype presentation, using the Oxford classification of stroke, into cortical and lacunar (small vessel disease) stroke. RESULTS The MetS was diagnosed in 151 T2D patients (62%), with 86 male and 65 female patients (age: 71.8+/-9.7). Comparing the MetS and non-MetS groups, the distribution of stroke subtypes adjusted for age and sex were: cortical stroke (13.2% versus 15.2%; P=0.56), lacunar stroke (43.7% versus 43.5%; P=0.87) and TIA (38.4% versus 39.1%; P=0.98). Lacunar stroke incidence was significantly higher compared to cortical stroke in both groups (P<0.001). CONCLUSION In this study of T2D patients, lacunar stroke (small vessel disease) was the most common stroke subtype in both patients with and without the MetS.
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Affiliation(s)
- Imtiaz M Shah
- Department of Medicine, The Ayr Hospital, Ayr, Scotland KA6 6DX, United Kingdom.
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Eguchi K, Pickering TG, Kario K. Why is blood pressure so hard to control in patients with type 2 diabetes? ACTA ACUST UNITED AC 2007; 2:114-8. [PMID: 17684464 DOI: 10.1111/j.1559-4564.2007.06124.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Resistance to antihypertensive drugs is common in hypertensive patients with type 2 diabetes. This is unfortunate because hypertension is one of the most important risk factors for development of cardiovascular events, and the goal blood pressure level is set lower in diabetic subjects than in nondiabetic subjects. Previous outcome trials in diabetic subjects have mainly focused on end points such as microalbuminuria or the incidence of cardiovascular events rather than on reduction of blood pressure; some reports, however, have suggested mechanisms for the drug resistance. These include several clinical conditions known to be associated with difficulty in reducing blood pressure specifically in diabetes mellitus: change in the renin-angiotensin system and chymase, volume overload, central sympathetic hyperactivity, sleep apnea, secondary hypertension, pseudoresistance (white coat hypertension), and poor compliance related to subclinical depression. In this review, the authors focus on the mechanisms of resistance to antihypertensive therapy (particularly for monotherapy with either angiotensin-converting enzyme inhibitors or angiotensin II antagonists) in the treatment of diabetic hypertension.
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Affiliation(s)
- Kazuo Eguchi
- Center for Behavioral Cardiovascular Health, Division of General Medicine, Columbia University Medical Center, New York, NY 10032, USA.
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Abstract
As the availability and quality of imaging techniques improve, doctors are identifying more patients with no history of transient ischaemic attack or stroke in whom imaging shows brain infarcts. Until recently, little was known about the relevance of these lesions. In this systematic review, we give an overview of the frequency, causes, and consequences of MRI-defined silent brain infarcts, which are detected in 20% of healthy elderly people and up to 50% of patients in selected series. Most infarcts are lacunes, of which hypertensive small-vessel disease is thought to be the main cause. Although silent infarcts, by definition, lack clinically overt stroke-like symptoms, they are associated with subtle deficits in physical and cognitive function that commonly go unnoticed. Moreover, the presence of silent infarcts more than doubles the risk of subsequent stroke and dementia. Future studies will have to show whether screening and treating high-risk patients can effectively reduce the risk of further infarcts, stroke, and dementia.
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Affiliation(s)
- Sarah E Vermeer
- Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
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Last D, de Bazelaire C, Alsop DC, Hu K, Abduljalil AM, Cavallerano J, Marquis RP, Novak V. Global and regional effects of type 2 diabetes on brain tissue volumes and cerebral vasoreactivity. Diabetes Care 2007; 30:1193-9. [PMID: 17290035 PMCID: PMC2031924 DOI: 10.2337/dc06-2052] [Citation(s) in RCA: 189] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation. RESEARCH DESIGN AND METHODS CBF was examined in 26 diabetic (aged 61.6 +/- 6.6 years) and 25 control (aged 60.4 +/- 8.6 years) subjects using continuous arterial spin labeling (CASL) imaging during baseline, hyperventilation, and CO2 rebreathing. Regional gray and white matter, cerebrospinal fluid (CSF), and white matter hyperintensity (WMH) volumes were measured on a T1-weighted inversion recovery fast-gradient echo and a fluid attenuation inversion recovery magnetic resonance imaging at 3 Tesla. RESULTS The diabetic group had smaller global white (P = 0.006) and gray (P = 0.001) matter and larger CSF (36.3%, P < 0.0001) volumes than the control group. Regional differences were observed for white matter (-13.1%, P = 0.0008) and CSF (36.3%, P < 0.0001) in the frontal region, for CSF (20.9%, P = 0.0002) in the temporal region, and for gray matter (-3.0%, P = 0.04) and CSF (17.6%, P = 0.01) in the parieto-occipital region. Baseline regional CBF (P = 0.006) and CO2 reactivity (P = 0.005) were reduced in the diabetic group. Hypoperfusion in the frontal region was associated with gray matter atrophy (P < 0.0001). Higher A1C was associated with lower CBF (P < 0.0001) and greater CSF (P = 0.002) within the temporal region. CONCLUSIONS Type 2 diabetes is associated with cortical and subcortical atrophy involving several brain regions and with diminished regional cerebral perfusion and vasoreactivity. Uncontrolled diabetes may further contribute to hypoperfusion and atrophy. Diabetic metabolic disturbance and blood flow dysregulation that affects preferentially frontal and temporal regions may have implications for cognition and balance in elderly subjects with diabetes.
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Affiliation(s)
- David Last
- Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Cedric de Bazelaire
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - David C. Alsop
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Kun Hu
- Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | | | - Jerry Cavallerano
- Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts
| | - Robert P. Marquis
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Vera Novak
- Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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Toyoda K, Okada Y, Jinnouchi J, Gotoh S, Yokoyama Y, Fujimoto S, Ibayashi S. High Blood Pressure in Acute Ischemic Stroke and Underlying Disorders. Cerebrovasc Dis 2006; 22:355-61. [PMID: 16888375 DOI: 10.1159/000094851] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2005] [Accepted: 03/29/2006] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) study indicated that early treatment with an angiotensin type 1 receptor blocker in acute stroke patients who had relatively high blood pressure improved cardiovascular morbidity and mortality in the chronic stage. To better interpret the findings of this study, we determined whether stroke patients with high acute blood pressure had specific underlying conditions. METHODS We divided 712 consecutive patients who were hospitalized within 48 h after the onset of brain infarction into two groups: 77 patients with high acute blood pressure that met the criteria of the ACCESS study and the 635 remaining patients. Underlying risk factors and comorbidities, stroke characteristics, as well as mortality, vascular events, and disability at 3 weeks were compared between the two groups. RESULTS Patients with high acute blood pressure more frequently had diabetes mellitus (p < 0.01), intracranial arterial stenosis (p < 0.02), higher levels of hemoglobin A1c (p < 0.005), higher creatinine levels (p < 0.005), and tended to more frequently have ischemic heart disease (p < 0.09) and infarcts <1.5 cm in diameter (p < 0.09) than the other patients. On multivariate analysis, high levels of hemoglobin A1c, high creatinine levels, and intracranial arterial stenosis were independently predictive of high acute blood pressure. At 3 weeks after the stroke onset, patients with high acute blood pressure were more dependent in their daily living activities (p < 0.02) and more frequently developed vascular events or death (p < 0.005) than the other patients. CONCLUSIONS Poorly controlled diabetes mellitus and advanced renal damage appeared to correlate with acute hypertension after stroke. Since intracranial arterial stenosis also seemed to contribute to high acute blood pressure, one should be careful not to induce cerebral hypoperfusion by the early use of antihypertensives.
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Affiliation(s)
- Kazunori Toyoda
- Department of Cerebrovascular Disease, Cerebrovascular Center and Clinical Research Institute, National Kyushu Medical Center, Fukuoka, Japan.
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van Harten B, de Leeuw FE, Weinstein HC, Scheltens P, Biessels GJ. Brain imaging in patients with diabetes: a systematic review. Diabetes Care 2006; 29:2539-48. [PMID: 17065699 DOI: 10.2337/dc06-1637] [Citation(s) in RCA: 262] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Barbera van Harten
- Medisch Centrum Leeuwarden, Postbus 888, 8901 BR Leeuwarden, Netherlands.
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Affiliation(s)
- Christopher M Ryan
- University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
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Toyoda K, Okada Y, Fujimoto S, Hagiwara N, Nakachi K, Kitazono T, Ibayashi S, Iida M. Blood pressure changes during the initial week after different subtypes of ischemic stroke. Stroke 2006; 37:2637-9. [PMID: 16946144 DOI: 10.1161/01.str.0000242781.80832.cc] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND PURPOSE The purpose of this study was to clarify the differences in the acute blood pressure course among different ischemic stroke subtypes. METHODS We divided 588 consecutive patients with acute brain infarction into four clinical subgroups to study the blood pressure levels during the initial 6 hospital days. RESULTS During the 6 days, systolic blood pressure of lacunar and atherothrombotic patients was higher (P=0.0001) and diastolic blood pressure of lacunar patients was higher (P=0.0371) than of patients with the other subtypes. Preexisting hypertension was associated with elevated acute systolic blood pressure in all patients and in each subtype and with elevated acute diastolic blood pressure in all patients, cardioembolic patients, and patients with stroke of other etiology. After adjustment by preexisting hypertension, diabetes mellitus with a hemoglobin A1c >7.0% was associated with elevated systolic blood pressure in all, lacunar, and cardioembolic patients and with diastolic blood pressure in all patients. CONCLUSIONS Blood pressure course of patients sustaining acute stroke varied widely according to stroke subtypes. Poorly controlled diabetes mellitus, as well as preexisting hypertension, appeared to influence blood pressure during the initial week of stroke.
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Affiliation(s)
- Kazunori Toyoda
- Department of Cerebrovascular Disease and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
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Novak V, Last D, Alsop DC, Abduljalil AM, Hu K, Lepicovsky L, Cavallerano J, Lipsitz LA. Cerebral blood flow velocity and periventricular white matter hyperintensities in type 2 diabetes. Diabetes Care 2006; 29:1529-34. [PMID: 16801574 PMCID: PMC1978169 DOI: 10.2337/dc06-0261] [Citation(s) in RCA: 124] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Diabetes increases the risk for cerebromicrovascular disease, possibly through its effects on blood flow regulation. The aim of this study was to assess the effects of type 2 diabetes on blood flow velocities (BFVs) in the middle cerebral arteries and to determine the relationship between white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) and BFVs. RESEARCH DESIGN AND METHODS We measured BFVs in 28 type 2 diabetic and 22 control subjects (aged 62.3 +/- 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO(2) rebreathing. WMHs were graded, and their volume was quantified from fluid-attenuated inversion recovery images on a 3.0 Tesla MRI. RESULTS The diabetic group demonstrated decreased mean BFVs and increased cerebrovascular resistance during baseline, hypo- and hypercapnia (P < 0.0001), and impaired CO(2) reactivity (P = 0.05). WMH volume was negatively correlated with baseline BFV (P < 0.0001). A regression model revealed that baseline BFVs were negatively associated with periventricular WMHs, HbA(1c) (A1C), and inflammatory markers and positively associated with systolic blood pressure (R(2) = 0.86, P < 0.0001). CONCLUSIONS Microvascular disease in type 2 diabetes, which manifests as white matter abnormalities on MRI, is associated with reduced cerebral BFVs, increased resistance in middle cerebral arteries, and inflammation. These findings are clinically relevant as a potential mechanism for cerebrovascular disease in elderly with type 2 diabetes.
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Affiliation(s)
- Vera Novak
- Division of Gerontology, Beth Israel Deaconess Medical Center, 110 Francis St., Boston, MA 02215, USA.
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Kario K. "Cocktail" antihypertensive chronotherapy for perfect control of morning hypertension in diabetic patients. Intern Med 2005; 44:1211-2. [PMID: 16415538 DOI: 10.2169/internalmedicine.44.1211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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