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Zhang H, Li Y, Zhan L, Long J, Shen J, Chen J, Qian J, Pan Z, Wu X, Wang Z, Wu W, Huang G. Knowledge domain and emerging trends in post-stroke cognitive impairment: a bibliometric analysis. Front Aging Neurosci 2025; 17:1525626. [PMID: 40103932 PMCID: PMC11913868 DOI: 10.3389/fnagi.2025.1525626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 02/17/2025] [Indexed: 03/20/2025] Open
Abstract
Background Cognitive impairment is an important cause of disability and death among the elderly. One of the most important risk factors is stroke. Post-stroke cognitive impairment (PSCI) not only diminishes the quality of life for patients but also increases the burden on families and society. But PSCI can be mitigated through early intervention. Cerebral small vessel disease (CSVD) is one of the significant causes of stroke and has garnered considerable attention in PSCI. Therefore, this study aims to identify research priorities and trends in PSCI through bibliometric analysis, and further explore the role played by CSVD in PSCI. Methods In this study, we performed a systematic search in the Science Citation Index Expanded (SCI-E) of the Web of Science Core Collection (WoSCC). VOSviewer, CiteSpace and Origin were mainly used to visualize the research focus and trend in PSCI. In addition, we screened the retrieved literature again, and performed keyword analysis on the studies related to CSVD. Results A total of 1,943 publications were retrieved in the field of PSCI in this study, with consistent upward trend in annual publications in recent years. Pendlebury was an important leader in PSCI research. Capital Medical University was in the leading position judging from the number of publications. China had the highest number of publications in this field. The journal Stroke had the strongest international influence in this field. Keywords such as "functional connectivity," "tool," "systematic review," and "meta-analysis" have been revealed to have momentous impact on PSCI in recent years. In the further analysis of PSCI and CSVD, "hypertension," "white matter hyperintensities (WMH)," "cerebral microbleeds (CMBs)," and "cerebral amyloid angiopathy (CAA)" received extensive attention. Conclusion The study of PSCI is still in the development stage. This study systematically summarizes the progress and development trend in the field of PSCI, and further explores the relationship between CSVD and PSCI through hypertension and magnetic resonance imaging markers. This study is of great significance for researchers to quickly understand the development of PSCI, but also helps them understand future directions, and provides important insights for the prevention and treatment of PSCI.
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Affiliation(s)
- Heyu Zhang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Yanwei Li
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Luqian Zhan
- Department of Neurology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China
| | - Jingfang Long
- Department of Neurology, Wenzhou Central Hospital, Wenzhou, China
| | - Jianing Shen
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Jiahui Chen
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Jiajing Qian
- Department of Mental Health, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Zhiming Pan
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Xue Wu
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Zhen Wang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou, China
| | - Wenjun Wu
- Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Affiliated With Wenzhou Medical University, Wenzhou, China
| | - Guiqian Huang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Affiliated With Wenzhou Medical University, Wenzhou, China
- School of Mental Health, Affiliated With Wenzhou Medical University, Wenzhou, China
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Alateeq K, Walsh EI, Cherbuin N. High Blood Pressure and Impaired Brain Health: Investigating the Neuroprotective Potential of Magnesium. Int J Mol Sci 2024; 25:11859. [PMID: 39595928 PMCID: PMC11594239 DOI: 10.3390/ijms252211859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 10/27/2024] [Accepted: 10/30/2024] [Indexed: 11/28/2024] Open
Abstract
High blood pressure (BP) is a significant contributor to the disease burden globally and is emerging as an important cause of morbidity and mortality in the young as well as the old. The well-established impact of high BP on neurodegeneration, cognitive impairment, and dementia is widely acknowledged. However, the influence of BP across its full range remains unclear. This review aims to explore in more detail the effects of BP levels on neurodegeneration, cognitive function, and dementia. Moreover, given the pressing need to identify strategies to reduce BP levels, particular attention is placed on reviewing the role of magnesium (Mg) in ageing and its capacity to lower BP levels, and therefore potentially promote brain health. Overall, the review aims to provide a comprehensive synthesis of the evidence linking BP, Mg and brain health. It is hoped that these insights will inform the development of cost-effective and scalable interventions to protect brain health in the ageing population.
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Affiliation(s)
- Khawlah Alateeq
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 2601, Australia; (K.A.); (E.I.W.)
- Radiological Science, College of Applied Medical Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Erin I. Walsh
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 2601, Australia; (K.A.); (E.I.W.)
| | - Nicolas Cherbuin
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 2601, Australia; (K.A.); (E.I.W.)
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Littig L, Sheth KN, Brickman AM, Mistry EA, de Havenon A. Blood Pressure and Cognitive Function in Older Adults. Clin Geriatr Med 2024; 40:597-613. [PMID: 39349034 PMCID: PMC11443062 DOI: 10.1016/j.cger.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Abstract
This review explores the extensive evidence linking hypertension with vascular cognitive impairment and dementia, emphasizing its role as a treatable risk factor. Drawing on observational data, it will elucidate how the chronicity of hypertension at different life stages amplifies cognitive decline risk. It explores the mechanisms underlying hypertension's association with dementia, assesses the neuroprotective properties of antihypertensive therapy, and evaluates novel blood pressure metrics and monitoring methods for their diagnostic and therapeutic potential in dementia management.
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Affiliation(s)
- Lauren Littig
- Department of Neurology, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Kevin N Sheth
- Department of Neurology, Yale University, 15 York Street, New Haven, CT 06510, USA; Center for Brain and Mind Health, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Adam M Brickman
- Department of Neurology, Columbia University Medical Center, 710 West 168 Street, New York, NY 10032, USA
| | - Eva A Mistry
- Department of Neurology and Rehabilitation Medicine, University of Cincinnati, 260 Stetson Street, Cincinnati, OH 45267, USA
| | - Adam de Havenon
- Department of Neurology, Yale University, 15 York Street, New Haven, CT 06510, USA; Center for Brain and Mind Health, Yale University, 15 York Street, New Haven, CT 06510, USA.
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Csiszar A, Ungvari A, Patai R, Gulej R, Yabluchanskiy A, Benyo Z, Kovacs I, Sotonyi P, Kirkpartrick AC, Prodan CI, Liotta EM, Zhang XA, Toth P, Tarantini S, Sorond FA, Ungvari Z. Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhages. GeroScience 2024; 46:5103-5132. [PMID: 38639833 PMCID: PMC11336042 DOI: 10.1007/s11357-024-01139-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 03/14/2024] [Indexed: 04/20/2024] Open
Abstract
Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). This review paper delves into the hypothesis that atherosclerosis, a prevalent age-related large vessel disease, extends its pathological influence into the cerebral microcirculation, thereby contributing to the development and progression of CSVD, with a specific focus on CMHs. We explore the concept of vascular aging as a continuum, bridging macrovascular pathologies like atherosclerosis with microvascular abnormalities characteristic of CSVD. We posit that the same risk factors precipitating accelerated aging in large vessels (i.e., atherogenesis), primarily through oxidative stress and inflammatory pathways, similarly instigate accelerated microvascular aging. Accelerated microvascular aging leads to increased microvascular fragility, which in turn predisposes to the formation of CMHs. The presence of hypertension and amyloid pathology further intensifies this process. We comprehensively overview the current body of evidence supporting this interconnected vascular hypothesis. Our review includes an examination of epidemiological data, which provides insights into the prevalence and impact of CMHs in the context of atherosclerosis and CSVD. Furthermore, we explore the shared mechanisms between large vessel aging, atherogenesis, microvascular aging, and CSVD, particularly focusing on how these intertwined processes contribute to the genesis of CMHs. By highlighting the role of vascular aging in the pathophysiology of CMHs, this review seeks to enhance the understanding of CSVD and its links to systemic vascular disorders. Our aim is to provide insights that could inform future therapeutic approaches and research directions in the realm of neurovascular health.
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Affiliation(s)
- Anna Csiszar
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Anna Ungvari
- Department of Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary.
| | - Roland Patai
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Rafal Gulej
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Andriy Yabluchanskiy
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Zoltan Benyo
- Institute of Translational Medicine, Semmelweis University, 1094, Budapest, Hungary
- Cerebrovascular and Neurocognitive Disorders Research Group, HUN-REN, Semmelweis University, 1094, Budapest, Hungary
| | - Illes Kovacs
- Department of Ophthalmology, Semmelweis University, 1085, Budapest, Hungary
- Department of Ophthalmology, Weill Cornell Medical College, New York, NY, 10021, USA
| | - Peter Sotonyi
- Department of Vascular and Endovascular Surgery, Heart and Vascular Centre, Semmelweis University, 1122, Budapest, Hungary
| | - Angelia C Kirkpartrick
- Veterans Affairs Medical Center, Oklahoma City, OK, USA
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Calin I Prodan
- Veterans Affairs Medical Center, Oklahoma City, OK, USA
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Eric M Liotta
- International Training Program in Geroscience, Doctoral College/Department of Public Health, Semmelweis University, Budapest, Hungary
- Department of Neurology, Division of Stroke and Neurocritical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Xin A Zhang
- Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA
| | - Peter Toth
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
- Neurotrauma Research Group, Szentagothai Research Centre, University of Pecs, Pecs, Hungary
- ELKH-PTE Clinical Neuroscience MR Research Group, University of Pecs, Pecs, Hungary
| | - Stefano Tarantini
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Farzaneh A Sorond
- Department of Neurology, Division of Stroke and Neurocritical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Department of Public Health, Semmelweis University, Budapest, Hungary
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Wu Z, Chen J, Liu Y, Yang Y, Feng M, Dai H. The Effects of PICALM rs3851179 and Age on Brain Atrophy and Cognition Along the Alzheimer's Disease Continuum. Mol Neurobiol 2024; 61:6984-6996. [PMID: 38363532 DOI: 10.1007/s12035-024-03953-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 01/12/2024] [Indexed: 02/17/2024]
Abstract
Rs3851179, a variant of PICALM gene, and age are the risk factors of Alzheimer's disease (AD). AD is divided into early-onset AD (EOAD, < 65 years) and late-onset AD (LOAD, ≥ 65 years) by age. The purpose was to investigate the impact of different genotypes of PICALM rs3851179 on brain atrophy and cognitive decline across the AD continuum in different age groups. Four hundred seven cognitive normal (CN) controls, 362 mild cognitive impairment (MCI) patients, and 94 AD patients were enrolled to assess the interaction between AD continuum, age status, and PICALM on gray matter volume (GMV), global cognition, memory function, and executive function using full factorial ANCOVA (3 × 2 × 2). The interaction between AD continuum and PICALM significantly affected the GMV of the left putamen (PUT.L). rs3851179 A-allele carriers did not show a significant decrease in PUT.L GMV from CN to MCI to AD, while GG-allele carriers did. The interaction between AD continuum and age status was significant on GMV of the left angular gyrus (ANG.L) and right superior occipital gyrus (SOG.R). LOAD had higher GMV of ANG.L and SOG.R than EOAD. The interactive effects among AD continuum, age status, and PICALM were not significant on GMV but were significant on global cognition and executive function. The A-allele was found to have a protective effect on global cognition and executive function in EOAD, but not significantly so in LOAD. PICALM rs3851179 A-allele might alleviate the atrophy of PUT.L across the AD continuum than GG-allele. Age status did not affect the interaction between AD continuum and PICALM on brain atrophy. The ANG.L and SOG.R atrophied more severely in EOAD than in LOAD. Rs3851179 A-allele was protective for global cognition and executive function in EOAD.
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Affiliation(s)
- Zhiwei Wu
- Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, 230001, People's Republic of China
| | - Jinhong Chen
- Department of Ultrasound, Hefei Hospital affiliated to Anhui Medical University: The Second People's Hospital of Hefei, Hefei, Anhui Province, 230011, People's Republic of China
- The Fifth Clinical Medical College of Anhui Medical University, Hefei, Anhui Province, 230032, People's Republic of China
| | - Yuanqing Liu
- Department of Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People's Republic of China
| | - Yiwen Yang
- Department of Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People's Republic of China
| | - Mengmeng Feng
- Department of Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People's Republic of China
| | - Hui Dai
- Department of Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People's Republic of China.
- Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu Province, 215006, People's Republic of China.
- Suzhou Key Laboratory of Intelligent Medicine and Equipment, Suzhou, Jiangsu Province, 215123, People's Republic of China.
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6
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Ungvari A, Gulej R, Csik B, Mukli P, Negri S, Tarantini S, Yabluchanskiy A, Benyo Z, Csiszar A, Ungvari Z. The Role of Methionine-Rich Diet in Unhealthy Cerebrovascular and Brain Aging: Mechanisms and Implications for Cognitive Impairment. Nutrients 2023; 15:4662. [PMID: 37960316 PMCID: PMC10650229 DOI: 10.3390/nu15214662] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 10/28/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
As aging societies in the western world face a growing prevalence of vascular cognitive impairment and Alzheimer's disease (AD), understanding their underlying causes and associated risk factors becomes increasingly critical. A salient concern in the western dietary context is the high consumption of methionine-rich foods such as red meat. The present review delves into the impact of this methionine-heavy diet and the resultant hyperhomocysteinemia on accelerated cerebrovascular and brain aging, emphasizing their potential roles in cognitive impairment. Through a comprehensive exploration of existing evidence, a link between high methionine intake and hyperhomocysteinemia and oxidative stress, mitochondrial dysfunction, inflammation, and accelerated epigenetic aging is drawn. Moreover, the microvascular determinants of cognitive deterioration, including endothelial dysfunction, reduced cerebral blood flow, microvascular rarefaction, impaired neurovascular coupling, and blood-brain barrier (BBB) disruption, are explored. The mechanisms by which excessive methionine consumption and hyperhomocysteinemia might drive cerebromicrovascular and brain aging processes are elucidated. By presenting an intricate understanding of the relationships among methionine-rich diets, hyperhomocysteinemia, cerebrovascular and brain aging, and cognitive impairment, avenues for future research and potential therapeutic interventions are suggested.
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Affiliation(s)
- Anna Ungvari
- Department of Public Health, Semmelweis University, 1089 Budapest, Hungary
| | - Rafal Gulej
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Boglarka Csik
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- International Training Program in Geroscience, Department of Public Health, Doctoral School of Basic and Translational Medicine, Semmelweis University, 1089 Budapest, Hungary
| | - Peter Mukli
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- International Training Program in Geroscience, Department of Public Health, Doctoral School of Basic and Translational Medicine, Semmelweis University, 1089 Budapest, Hungary
| | - Sharon Negri
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Stefano Tarantini
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- International Training Program in Geroscience, Department of Public Health, Doctoral School of Basic and Translational Medicine, Semmelweis University, 1089 Budapest, Hungary
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Andriy Yabluchanskiy
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- International Training Program in Geroscience, Department of Public Health, Doctoral School of Basic and Translational Medicine, Semmelweis University, 1089 Budapest, Hungary
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Zoltan Benyo
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary;
- Cerebrovascular and Neurocognitive Disorders Research Group, Eötvös Loránd Research Network, Semmelweis University, 1094 Budapest, Hungary
| | - Anna Csiszar
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- International Training Program in Geroscience, Department of Translational Medicine, Doctoral School of Basic and Translational Medicine, Semmelweis University, 1089 Budapest, Hungary
| | - Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (R.G.); (B.C.); (P.M.); (S.N.); (S.T.); (A.Y.); (A.C.); (Z.U.)
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- International Training Program in Geroscience, Department of Public Health, Doctoral School of Basic and Translational Medicine, Semmelweis University, 1089 Budapest, Hungary
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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7
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Mladenov M, Lubomirov L, Grisk O, Avtanski D, Mitrokhin V, Sazdova I, Keremidarska-Markova M, Danailova Y, Nikolaev G, Konakchieva R, Gagov H. Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging. Antioxidants (Basel) 2023; 12:antiox12051126. [PMID: 37237992 DOI: 10.3390/antiox12051126] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/22/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
This review is focused on the mechanisms that regulate health, disease and aging redox status, the signal pathways that counteract oxidative and reductive stress, the role of food components and additives with antioxidant properties (curcumin, polyphenols, vitamins, carotenoids, flavonoids, etc.), and the role of the hormones irisin and melatonin in the redox homeostasis of animal and human cells. The correlations between the deviation from optimal redox conditions and inflammation, allergic, aging and autoimmune responses are discussed. Special attention is given to the vascular system, kidney, liver and brain oxidative stress processes. The role of hydrogen peroxide as an intracellular and paracrine signal molecule is also reviewed. The cyanotoxins β-N-methylamino-l-alanine (BMAA), cylindrospermopsin, microcystins and nodularins are introduced as potentially dangerous food and environment pro-oxidants.
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Affiliation(s)
- Mitko Mladenov
- Faculty of Natural Sciences and Mathematics, Institute of Biology, "Ss. Cyril and Methodius" University, P.O. Box 162, 1000 Skopje, North Macedonia
| | - Lubomir Lubomirov
- Institute of Physiology, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany
| | - Olaf Grisk
- Institute of Physiology, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany
| | - Dimiter Avtanski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, 110 E 59th Street, New York, NY 10003, USA
| | - Vadim Mitrokhin
- Department of Physiology, Pirogov Russian National Research Medical University, 1 Ostrovityanova Street, 117997 Moscow, Russia
| | - Iliyana Sazdova
- Department of Animal and Human Physiology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria
| | - Milena Keremidarska-Markova
- Department of Animal and Human Physiology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria
| | - Yana Danailova
- Department of Animal and Human Physiology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria
| | - Georgi Nikolaev
- Department of Cell and Developmental Biology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria
| | - Rossitza Konakchieva
- Department of Cell and Developmental Biology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria
| | - Hristo Gagov
- Department of Animal and Human Physiology, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria
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8
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Miao SH, Gao SQ, Li HX, Zhuang YS, Wang X, Li T, Gao CC, Han YL, Qiu JY, Zhou ML. Increased NOX2 expression in astrocytes leads to eNOS uncoupling through dihydrofolate reductase in endothelial cells after subarachnoid hemorrhage. Front Mol Neurosci 2023; 16:1121944. [PMID: 37063365 PMCID: PMC10097896 DOI: 10.3389/fnmol.2023.1121944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/13/2023] [Indexed: 04/03/2023] Open
Abstract
IntroductionEndothelial nitric oxide synthase (eNOS) uncoupling plays a significant role in acute vasoconstriction during early brain injury (EBI) after subarachnoid hemorrhage (SAH). Astrocytes in the neurovascular unit extend their foot processes around endothelia. In our study, we tested the hypothesis that increased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression in astrocytes after SAH leads to eNOS uncoupling.MethodsWe utilized laser speckle contrast imaging for monitoring cortical blood flow changes in mice, nitric oxide (NO) kits to measure the level of NO, and a co-culture system to study the effect of astrocytes on endothelial cells. Moreover, the protein levels were assessed by Western blot and immunofluorescence staining. We used CCK-8 to measure the viability of astrocytes and endothelial cells, and we used the H2O2 kit to measure the H2O2 released from astrocytes. We used GSK2795039 as an inhibitor of NOX2, whereas lentivirus and adeno-associated virus were used for dihydrofolate reductase (DHFR) knockdown in vivo and in vitro.ResultsThe expression of NOX2 and the release of H2O2 in astrocytes are increased, which was accompanied by a decrease in endothelial DHFR 12 h after SAH. Moreover, the eNOS monomer/dimer ratio increased, leading to a decrease in NO and acute cerebral ischemia. All of the above were significantly alleviated after the administration of GSK2795039. However, after knocking down DHFR both in vivo and in vitro, the protective effect of GSK2795039 was greatly reversed.DiscussionThe increased level of NOX2 in astrocytes contributes to decreased DHFR in endothelial cells, thus aggravating eNOS uncoupling, which is an essential mechanism underlying acute vasoconstriction after SAH.
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Affiliation(s)
- Shu-Hao Miao
- Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Sheng-Qing Gao
- Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Hui-Xin Li
- Department of Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing, China
| | - Yun-Song Zhuang
- Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Xue Wang
- Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Tao Li
- Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Chao-Chao Gao
- Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Yan-Ling Han
- Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jia-Yin Qiu
- Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Meng-Liang Zhou
- Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical Medicine, Nanjing Medical University, Nanjing, China
- *Correspondence: Meng-Liang Zhou,
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9
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Liu Q, Zhang X. Multimodality neuroimaging in vascular mild cognitive impairment: A narrative review of current evidence. Front Aging Neurosci 2023; 15:1073039. [PMID: 37009448 PMCID: PMC10050753 DOI: 10.3389/fnagi.2023.1073039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 02/24/2023] [Indexed: 03/17/2023] Open
Abstract
The vascular mild cognitive impairment (VaMCI) is generally accepted as the premonition stage of vascular dementia (VaD). However, most studies are focused mainly on VaD as a diagnosis in patients, thus neglecting the VaMCI stage. VaMCI stage, though, is easily diagnosed by vascular injuries and represents a high-risk period for the future decline of patients' cognitive functions. The existing studies in China and abroad have found that magnetic resonance imaging technology can provide imaging markers related to the occurrence and development of VaMCI, which is an important tool for detecting the changes in microstructure and function of VaMCI patients. Nevertheless, most of the existing studies evaluate the information of a single modal image. Due to the different imaging principles, the data provided by a single modal image are limited. In contrast, multi-modal magnetic resonance imaging research can provide multiple comprehensive data such as tissue anatomy and function. Here, a narrative review of published articles on multimodality neuroimaging in VaMCI diagnosis was conducted，and the utilization of certain neuroimaging bio-markers in clinical applications was narrated. These markers include evaluation of vascular dysfunction before tissue damages and quantification of the extent of network connectivity disruption. We further provide recommendations for early detection, progress, prompt treatment response of VaMCI, as well as optimization of the personalized treatment plan.
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Affiliation(s)
- Qiuping Liu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xuezhu Zhang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
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10
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Gunraj RE, Yang C, Liu L, Larochelle J, Candelario-Jalil E. Protective roles of adropin in neurological disease. Am J Physiol Cell Physiol 2023; 324:C674-C678. [PMID: 36717106 PMCID: PMC10027081 DOI: 10.1152/ajpcell.00318.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 01/18/2023] [Accepted: 01/23/2023] [Indexed: 02/01/2023]
Abstract
Adropin is a highly conserved secreted peptide encoded by the Energy Homeostasis Associated gene (Enho). It is expressed in many tissues throughout the body, including the liver and brain, and plays a crucial role in maintaining lipid homeostasis and regulating insulin sensitivity. Adropin also participates in several other pathophysiological processes of multiple central nervous system (CNS) diseases. There is strong evidence of the protective effects of adropin in stroke, heart disease, aging, and other diseases. The peptide has been shown to reduce the risk of disease, attenuate histological alterations, and reduce cognitive decline associated with neurological disorders. Recent findings support its critical role in regulating endothelial cells and maintaining blood-brain barrier integrity through an endothelial nitric oxide synthase (eNOS)-dependent mechanism. Here we discuss current evidence of the protective effects of adropin in CNS diseases specifically involving the cerebrovasculature and highlight potential mechanisms through which the peptide exhibits these effects.
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Affiliation(s)
- Rachel E Gunraj
- Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States
| | - Changjun Yang
- Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States
| | - Lei Liu
- Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States
| | - Jonathan Larochelle
- Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States
| | - Eduardo Candelario-Jalil
- Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, United States
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11
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White Matter Injury: An Emerging Potential Target for Treatment after Subarachnoid Hemorrhage. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:3842493. [PMID: 36798684 PMCID: PMC9928519 DOI: 10.1155/2023/3842493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 12/20/2022] [Accepted: 01/04/2023] [Indexed: 02/10/2023]
Abstract
Subarachnoid hemorrhage (SAH) refers to vascular brain injury mainly from a ruptured aneurysm, which has a high lifetime risk and imposes a substantial burden on patients, families, and society. Previous studies on SAH mainly focused on neurons in gray matter (GM). However, according to literature reports in recent years, in-depth research on the mechanism of white matter (WM) is of great significance to injury and recovery after SAH. In terms of functional recovery after SAH, all kinds of cells in the central nervous system (CNS) should be protected. In other words, it is necessary to protect not only GM but also WM, not only neurons but also glial cells and axons, and not only for the lesion itself but also for the prevention and treatment of remote damage. Clarifying the mechanism of white matter injury (WMI) and repair after SAH is of great importance. Therefore, this present review systematically summarizes the current research on WMI after SAH, which might provide therapeutic targets for treatment after SAH.
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12
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Kiyohara T, Kumai Y, Yubi T, Ishikawa E, Wakisaka Y, Ago T, Kitazono T. Association between Early Cognitive Impairment and Short-Term Functional Outcome in Acute Ischemic Stroke. Cerebrovasc Dis 2023; 52:61-67. [PMID: 35662179 DOI: 10.1159/000524839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 04/12/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Little is known about the association between poststroke cognitive impairment (PSCI) and functional outcome in the acute care phase of ischemic stroke and the influence of the clinical condition of acute stroke on this association. We examined this issue, taking into account stroke-related factors, in a hospital-based prospective study of patients with acute ischemic stroke. The same analysis was also performed after subsequent rehabilitation to investigate whether the association observed in the acute care phase persisted after that. For comparison, the same analysis was performed for pre-stroke dementia (PreSD). METHODS We included in the study a total of 923 patients with acute ischemic stroke who were admitted to a hospital from 2012 to 2020 in Japan. Cognitive function was assessed using the Mini-Mental State Examination and Raven's Colored Progressive Matrices test at an average of 6.3 days after stroke onset. The subjects were divided into three groups with normal cognition, PSCI, and PreSD. Study outcome was a poor functional outcome, defined as a modified Rankin Scale score of ≥3 at the end of acute care (median 21 days after admission). Among total subjects, 460 were also assessed for poor functional outcome after rehabilitation (median 77 days after admission). A logistic regression model was applied in this study. RESULTS Patients with PSCI and PreSD had higher median National Institute of Health Stroke Scale scores than those with normal cognition (median [IQR]: 3 [2-6], 4 [2-12], and 2 [1-4], respectively). The age- and sex-adjusted cumulative incidence of poor functional outcome was significantly higher in patients with PSCI and PreSD than in those with normal cognition in the acute care and rehabilitation phases. In the acute care phase, these associations remained significant after adjustment for stroke-related factors and other confounders (multivariable-adjusted odds ratio [95% CI] for PSCI vs. normal cognition: 3.28 [2.07-5.20]; for PreSD: 2.39 [1.40-4.08]). Similar results were observed in the rehabilitation phase (for PSCI: 2.48 [1.31-4.70]; for PreSD: 3.92 [1.94-7.92]). CONCLUSIONS Our findings suggest that PSCI, as well as PreSD, is possibly associated with the development of poor functional outcome in the acute care phase of ischemic stroke, and this association continues thereafter.
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Affiliation(s)
- Takuya Kiyohara
- Department of Cerebrovascular Disease and Neurology, Hakujyuji Hospital, Fukuoka, Japan.,Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasuhiro Kumai
- Department of Cerebrovascular Disease and Neurology, Hakujyuji Hospital, Fukuoka, Japan.,Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomohiro Yubi
- Department of Cerebrovascular Disease and Neurology, Hakujyuji Hospital, Fukuoka, Japan.,Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eiichi Ishikawa
- Department of Cerebrovascular Disease and Neurology, Hakujyuji Hospital, Fukuoka, Japan.,Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshinobu Wakisaka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tetsuro Ago
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.,Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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13
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Bickel MA, Csik B, Gulej R, Ungvari A, Nyul-Toth A, Conley SM. Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis. Front Endocrinol (Lausanne) 2023; 14:1087053. [PMID: 36755922 PMCID: PMC9900125 DOI: 10.3389/fendo.2023.1087053] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 01/04/2023] [Indexed: 01/24/2023] Open
Abstract
Age-related cerebrovascular pathologies, ranging from cerebromicrovascular functional and structural alterations to large vessel atherosclerosis, promote the genesis of vascular cognitive impairment and dementia (VCID) and exacerbate Alzheimer's disease. Recent advances in geroscience, including results from studies on heterochronic parabiosis models, reinforce the hypothesis that cell non-autonomous mechanisms play a key role in regulating cerebrovascular aging processes. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) exert multifaceted vasoprotective effects and production of both hormones is significantly reduced in aging. This brief overview focuses on the role of age-related GH/IGF-1 deficiency in the development of cerebrovascular pathologies and VCID. It explores the mechanistic links among alterations in the somatotropic axis, specific macrovascular and microvascular pathologies (including capillary rarefaction, microhemorrhages, impaired endothelial regulation of cerebral blood flow, disruption of the blood brain barrier, decreased neurovascular coupling, and atherogenesis) and cognitive impairment. Improved understanding of cell non-autonomous mechanisms of vascular aging is crucial to identify targets for intervention to promote cerebrovascular and brain health in older adults.
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Affiliation(s)
- Marisa A. Bickel
- Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Boglarka Csik
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Rafal Gulej
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
| | - Anna Ungvari
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- International Training Program in Geroscience, Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Adam Nyul-Toth
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- International Training Program in Geroscience, Department of Public Health, Semmelweis University, Budapest, Hungary
- Institute of Biophysics, Biological Research Centre, Eötvös Lorand Research Network (ELKH), Szeged, Hungary
| | - Shannon M. Conley
- Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
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14
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Solé-Guardia G, Custers E, de Lange A, Clijncke E, Geenen B, Gutierrez J, Küsters B, Claassen JAHR, de Leeuw FE, Wiesmann M, Kiliaan AJ. Association between hypertension and neurovascular inflammation in both normal-appearing white matter and white matter hyperintensities. Acta Neuropathol Commun 2023; 11:2. [PMID: 36600303 PMCID: PMC9811756 DOI: 10.1186/s40478-022-01497-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 12/19/2022] [Indexed: 01/05/2023] Open
Abstract
The major vascular cause of dementia is cerebral small vessel disease (SVD), including white matter hyperintensities (WMH) amongst others. While the underlying pathology of SVD remains unclear, chronic hypertension and neuroinflammation are recognized as important risk factors for SVD and for the conversion of normal-appearing white matter (NAWM) to WMH. Unfortunately, most studies investigating the role of neuroinflammation in WMH relied on peripheral blood markers, e.g., markers for systemic or vascular inflammation, as a proxy for inflammation in the brain itself. However, it is unknown whether such markers accurately capture inflammatory changes within the cerebral white matter. Therefore, we aimed to comprehensively investigate the impact of hypertension on perivascular- and neuroinflammation in both WMH and NAWM. We conducted high field brain magnetic resonance imaging (MRI), followed by (immuno-)histopathological staining of neuroinflammatory markers on human post-mortem brains of elderly people with a history of hypertension (n = 17) and age-matched normotensive individuals (n = 5). MRI images were co-registered to (immuno-)histopathological data including stainings for microglia and astroglia to assess changes in MRI-based WMH at microscopic resolution. Perivascular inflammation was carefully assessed based on the severity of perivascular astrogliosis of the smallest vessels throughout white matter regions. Hypertension was associated with a larger inflammatory response in both WMH and NAWM. Notably, the presence of close-range perivascular inflammation was twice as common among those with hypertension than in controls both in WMH and NAWM, suggesting that neurovascular inflammation is critical in the etiology of WMH. Moreover, a higher degree of microglial activation was related to a higher burden of WMH. Our results indicate that neuro(vascular)inflammation at the level of the brain itself is involved in the etiology of WMH. Future therapeutic strategies focusing on multitarget interventions including antihypertensive treatment as well as neuroinflammation may ameliorate WMH progression.
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Affiliation(s)
- Gemma Solé-Guardia
- grid.10417.330000 0004 0444 9382Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands
| | - Emma Custers
- grid.10417.330000 0004 0444 9382Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands
| | - Arthur de Lange
- grid.10417.330000 0004 0444 9382Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands
| | - Elyne Clijncke
- grid.10417.330000 0004 0444 9382Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands
| | - Bram Geenen
- grid.10417.330000 0004 0444 9382Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands
| | - Jose Gutierrez
- grid.239585.00000 0001 2285 2675Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Medical Center, New York, NY USA
| | - Benno Küsters
- grid.10417.330000 0004 0444 9382Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jurgen A. H. R. Claassen
- grid.10417.330000 0004 0444 9382Department of Geriatrics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Radboud Alzheimer Center, Nijmegen, The Netherlands
| | - Frank-Erik de Leeuw
- grid.10417.330000 0004 0444 9382Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Nijmegen, The Netherlands
| | - Maximilian Wiesmann
- grid.10417.330000 0004 0444 9382Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands
| | - Amanda J. Kiliaan
- grid.10417.330000 0004 0444 9382Department of Medical Imaging, Anatomy, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, The Netherlands
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15
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Xin Y, Chen J, Zhang H, Ostrowski RP, Liang Y, Zhao J, Xiang X, Liang F, Fu W, Huang H, Wu X, Su J, Deng J, He Z. Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage. Cells 2022; 11:2976. [PMID: 36230939 PMCID: PMC9564295 DOI: 10.3390/cells11192976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 09/10/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
White matter damage (WMD), one of the research hotspots of subarachnoid hemorrhage (SAH), mainly manifests itself as myelin injury and oligodendrocyte differentiation disorder after SAH, although the specific mechanism remains unclear. Dexamethasone-induced Ras-related protein 1(Dexras1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis. However, whether Dexras1 participates in dysdifferentiation of oligodendrocytes and myelin injury after SAH has yet to be examined, which is the reason for creating the research content of this article. Here, intracerebroventricular lentiviral administration was used to modulate Dexras1 levels in order to determine its functional influence on neurological injury after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting methods, were used to investigate the effects of Dexras1 on demyelination, glial cell activation, and differentiation of oligodendrocyte progenitor cells (OPCs) after SAH. Primary rat brain neurons were treated with oxyhemoglobin to verify the association between Dexras1 and cAMP-CREB. The results showed that Dexras1 levels were significantly increased upon in vivo SAH model, accompanied by OPC differentiation disturbances and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH. In contrast, Dexras1 knockdown ameliorated myelin injury, OPC dysdifferentiation, and glial cell activation. Further research of the underlying mechanism discovered that the cAMP-CREB pathway was inhibited after Dexras1 overexpression in the in vitro model of SAH. This study is the first to confirm that Dexras1 induced oligodendrocyte dysdifferentiation and myelin injury after SAH by inhibiting the cAMP-CREB pathway. This present research may reveal novel therapeutic targets for the amelioration of brain injury and neurological dysfunction after SAH.
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Affiliation(s)
- Yuanjun Xin
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Jie Chen
- Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Hongxia Zhang
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Robert P. Ostrowski
- Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Institute Polish Academy of Sciences, 02-106 Warsaw, Poland
| | - Yidan Liang
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Jun Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Xiang Xiang
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Fuming Liang
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Wenqiao Fu
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Hao Huang
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Xintong Wu
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Jun Su
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Jiewen Deng
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
| | - Zhaohui He
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Chongqing 400016, China
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16
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Yu H, Ding S, Wei W, Guo F, Li Z, Yuan Q, Zhao X. Impact of Pre-Stroke Dementia or Mild Cognitive Impairment on Stroke Outcome: A Systematic Review and Meta-Analysis. Dement Geriatr Cogn Disord 2022; 51:101-109. [PMID: 35405675 DOI: 10.1159/000522302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 12/21/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Pre-stroke dementia (PSD) and pre-stroke mild cognitive impairment (PSMCI) are important risk factors for stroke. The present meta-analysis aimed to investigate the impact of PSD or PSMCI on stroke outcomes. METHODS Electronic databases (PubMed, EMbase, Google Scholar, Cochrane Library, and TRIP) were screened for eligible studies published prior to March 31, 2021. Risk ratios (RR) and mean differences with 95% confidence intervals (CIs) using random or fixed effect models were used to calculate pooled estimates. Study quality was assessed using the Newcastle Ottawa Scale. RESULTS Fifteen studies were included in our meta-analysis. Pooled data from ten studies involving 3,107 PSD and 20,645 non-PSD subjects showed a higher risk of mortality in PSD patients (RR = 2.03; 95% CI: 1.40-2.91; I2 = 89%). Risk of recurrent stroke risk was observed more in patients with PSD compared to non-PSD patients (RR = 2.02; 95% CI: 1.40-2.91; I2 = 0%). Three studies involving 300 mild cognitive impairment (MCI) and 1,025 normal cognition subjects showed a significant increased risk of mortality in stroke patients with MCI (RR = 2.43; 95% CI: 1.81-3.27; I2 = 20%). However, elevated stroke severity was not observed in PSMCI patients. CONCLUSIONS Our meta-analysis shows an increased risk of mortality in stroke patients with a history of PSD and PSMCI. Proper clinical management and increased attention are therefore required for the prevention and management of stroke in patients with cognitive deficits.
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Affiliation(s)
- Huanqing Yu
- Department of Geriatrics, Qingdao Fifth People's Hospital, Qingdao, China
| | - Shufang Ding
- Department of Geriatrics, Qingdao Fifth People's Hospital, Qingdao, China
| | - Wei Wei
- Department of Geriatrics, Qingdao Fuwai Cardiovascular Hospital, Qingdao, China
| | - Feng Guo
- Department of Supply Room, Qingdao Fifth People's Hospital, Qingdao, China
| | - Zhongnan Li
- Department of Emergency, Qingdao Fifth People's Hospital, Qingdao, China
| | - Quan Yuan
- Department of Preventive Medicine, Qingdao Fifth People's Hospital, Qingdao, China
| | - Xin Zhao
- Department of First Stationed Outpatient, No. 971 PLA Hospital, Qingdao, China
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17
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Whitehead SN, Bruno A, Burns JM, Carmichael ST, Csiszar A, Edwards JD, Elahi FM, Faraco G, Gould DB, Gustafson DR, Hachinski V, Rosenberg G, Sorond FA, Shih AY, Tse KH, Ungvari Z, Wilcock DM, Zuloaga KL, Barone FC. Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition. GeroScience 2022; 44:25-37. [PMID: 34606040 PMCID: PMC8488071 DOI: 10.1007/s11357-021-00461-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 12/14/2022] Open
Abstract
White matter pathologies are critically involved in the etiology of vascular cognitive impairment-dementia (VCID), Alzheimer's disease (AD), and Alzheimer's disease and related diseases (ADRD), and therefore need to be considered a treatable target ( Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793-4, [1] . To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of "The Albert Research Institute for White Matter and Cognition" in 2020. The first annual "Institute" meeting was held virtually on March 3-4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust-sponsored workshops (Barone et al. in J Transl Med 14:1-14, [2]; Sorond et al. in GeroScience 42:81-96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop.
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Affiliation(s)
- Shawn N Whitehead
- Department of Anatomy and Cell Biology, Western University, London, ON, N6A 3K7, Canada.
| | - Askiel Bruno
- Department of Neurology, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA
| | - Jeffrey M Burns
- Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA
| | - S Thomas Carmichael
- Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA
| | - Anna Csiszar
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Jodi D Edwards
- University of Ottawa Heart Institute, Ottawa, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, K1G 5Z3, Canada
| | - Fanny M Elahi
- Memory and Aging Center, UCSF Weill Institute for Neurosciences, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA
| | - Giuseppe Faraco
- Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, 10065, USA
| | - Douglas B Gould
- Departments of Ophthalmology and Anatomy, and Institute for Human Genetics, School of Medicine, University of California, San Francisco, 94143, USA
| | - Deborah R Gustafson
- Department of Neurology, Section for NeuroEpidemiology, State University of New York Downstate Health Sciences University, New York, Brooklyn, 11203, USA
| | - Vladimir Hachinski
- Department of Clinical Neurological Sciences, Western University, London, ON, N6A 5C1, Canada
| | - Gary Rosenberg
- UNM Health Sciences Center, University of New Mexico, Albuquerque, NM, 87106, USA
| | | | - Andy Y Shih
- Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute; Department of Pediatrics; Department of Bioengineering, University of Washington, Seattle, WA, USA
| | - Kai Hei Tse
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Zoltan Ungvari
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Donna M Wilcock
- Sanders-Brown Center on Aging; Department of Neurology, Department of Behavioral Science, University of Kentucky, Lexington, KY, 40536, USA
| | - Kristen L Zuloaga
- Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, 12208, USA
| | - Frank C Barone
- Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, NY, 11203, USA
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18
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Craig L, Hoo ZL, Yan TZ, Wardlaw J, Quinn TJ. Prevalence of dementia in ischaemic or mixed stroke populations: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2022; 93:180-187. [PMID: 34782389 PMCID: PMC8784999 DOI: 10.1136/jnnp-2020-325796] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 08/30/2021] [Indexed: 12/24/2022]
Abstract
An understanding of the epidemiology of poststroke dementia (PSD) is necessary to inform research, practice and policy. With increasing primary studies, a contemporary review of PSD could allow for analyses of incidence and prevalence trends. Databases were searched using a prespecified search strategy. Eligible studies described an ischaemic or mixed stroke cohort with prospective clinical assessment for dementia. Pooled prevalence of dementia was calculated using random-effects models at any time after stroke (primary outcome) and at 1 year (range: 6-18 months), stratified for inclusion of prestroke dementia. Meta-regression explored the effect of year of study. Sensitivity analyses removed low-quality or outlier studies. Of 12 505 titles assessed, 44 studies were included in the quantitative analyses. At any time point after stroke, the prevalence of PSD was 16.5% (95% CI 10.4% to 25.1%) excluding prestroke dementia and 22.3% (95% CI 18.8% to 26.2%) including prestroke dementia. At 1 year, the prevalence of PSD was 18.4% (95% CI 7.4% to 38.7%) and 20.4% (95% CI 14.2% to 28.2%) with prestroke dementia included. In studies including prestroke dementia there was a negative association between dementia prevalence and year of study (slope coefficient=-0.05 (SD: 0.01), p<0.0001). Estimates were robust to sensitivity analyses. Dementia is common following stroke. At any point following stroke, more than one in five people will have dementia, although a proportion of this dementia predates the stroke. Declining prevalence of prestroke dementia may explain apparent reduction in PSD over time. Risk of dementia following stroke remains substantial and front-loaded, with high prevalence at 1 year post event.
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Affiliation(s)
- Louise Craig
- Institute of Cardiovascular and Medical Sciences, University of Glasgow College of Medical, Veterinary and Life Sciences, Glasgow, UK
| | - Zhi Liang Hoo
- Institute of Cardiovascular and Medical Sciences, University of Glasgow College of Medical, Veterinary and Life Sciences, Glasgow, UK
| | - Toh Zeng Yan
- Geriatric Medicine, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
| | - Joanna Wardlaw
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - Terence J Quinn
- Institute of Cardiovascular and Medical Sciences, University of Glasgow College of Medical, Veterinary and Life Sciences, Glasgow, UK
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19
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Ma LY, He F, Liu S, Wang XD, Gao Y, Shi Z, Niu J, Ji Y. The Association Between the Prevalence, Medication Adherence and Control of Hypertension and the Prevalence of Mild Cognitive Impairment in Rural Northern China: A Cross-Sectional Study. Patient Prefer Adherence 2022; 16:493-502. [PMID: 35228797 PMCID: PMC8882022 DOI: 10.2147/ppa.s351588] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 01/28/2022] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION High blood pressure is one of the main modifiable risk factors for dementia. However, it remains unclear whether lowering the blood pressure effectively prevents cognitive impairment. Our objective was to explore the association between the prevalence, medication adherence and control of hypertension and mild cognitive impairment (MCI) among elderly individuals in northern China. METHODS A two-stage clustering sampling method was used, and 9036 participants aged ≥65 years were included in the analysis. The Mini-Mental State Examination and activities of daily living were used to assess participants' cognitive function. Demographic characteristics (gender, age, marital status, education level, occupation), history and duration of hypertension, use of antihypertensive medications (AHMs) and its control effect were obtained. RESULTS The prevalence of MCI in all participants was 18.1%, and the prevalence of MCI was significantly higher in hypertensive subjects than in normotensive subjects (19.7% vs 16.2%, P < 0.01). Furthermore, in hypertensive patients, the prevalence of MCI was lower in those with good adherence (17.3%) than in those with poor adherence (23.7%, P < 0.01) and lower in those controlled (16.5%) than in those with uncontrolled adherence (20.8%, P < 0.01). In univariate analyses, being female gender, increased age, agriculture occupation, unmarried and widow, less than primary school and middle school were associated with MCI prevalence. The assessment of the hypertensive patients revealed the adjusted OR (95% CI) of having MCI in those with poor adherence to AHMs was 1.32 (1.14-1.54) compared with those having good adherence. CONCLUSION There is an association between the prevalence of hypertension, adherence to AHMs and MCI, suggesting that hypertensives should be screened for MCI to provide improved diagnoses and optimal therapeutics for cognitive decline prevention, especially in poor AHM adherence.
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Affiliation(s)
- Ling-Yun Ma
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Fangfang He
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, People’s Republic of China
| | - Shuai Liu
- Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China
| | - Xiao-Dan Wang
- Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China
| | - Yanqin Gao
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, People’s Republic of China
| | - Zhihong Shi
- Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China
- China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China
| | - Jianping Niu
- Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, People’s Republic of China
- Correspondence: Jianping Niu; Yong Ji, Tel +8618059218208; +8613612048681, Email ; ;
| | - Yong Ji
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China
- Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Department of Neurology, Tianjin Dementia Institute, Tianjin Huanhu Hospital, Tianjin, People’s Republic of China
- China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China
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20
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Ungvari Z, Toth P, Tarantini S, Prodan CI, Sorond F, Merkely B, Csiszar A. Hypertension-induced cognitive impairment: from pathophysiology to public health. Nat Rev Nephrol 2021; 17:639-654. [PMID: 34127835 PMCID: PMC8202227 DOI: 10.1038/s41581-021-00430-6] [Citation(s) in RCA: 255] [Impact Index Per Article: 63.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2021] [Indexed: 02/06/2023]
Abstract
Hypertension affects two-thirds of people aged >60 years and significantly increases the risk of both vascular cognitive impairment and Alzheimer's disease. Hypertension compromises the structural and functional integrity of the cerebral microcirculation, promoting microvascular rarefaction, cerebromicrovascular endothelial dysfunction and neurovascular uncoupling, which impair cerebral blood supply. In addition, hypertension disrupts the blood-brain barrier, promoting neuroinflammation and exacerbation of amyloid pathologies. Ageing is characterized by multifaceted homeostatic dysfunction and impaired cellular stress resilience, which exacerbate the deleterious cerebromicrovascular effects of hypertension. Neuroradiological markers of hypertension-induced cerebral small vessel disease include white matter hyperintensities, lacunar infarcts and microhaemorrhages, all of which are associated with cognitive decline. Use of pharmaceutical and lifestyle interventions that reduce blood pressure, in combination with treatments that promote microvascular health, have the potential to prevent or delay the pathogenesis of vascular cognitive impairment and Alzheimer's disease in patients with hypertension.
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Affiliation(s)
- Zoltan Ungvari
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Peter Toth
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
- Department of Neurosurgery, Medical School, University of Pecs, Pecs, Hungary
| | - Stefano Tarantini
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Calin I Prodan
- Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Veterans Affairs Medical Center, Oklahoma City, OK, USA
| | - Farzaneh Sorond
- Department of Neurology, Division of Stroke and Neurocritical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Bela Merkely
- Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Anna Csiszar
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
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21
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Sun Y, Xu S, Jiang M, Liu X, Yang L, Bai Z, Yang Q. Role of the Extracellular Matrix in Alzheimer's Disease. Front Aging Neurosci 2021; 13:707466. [PMID: 34512308 PMCID: PMC8430252 DOI: 10.3389/fnagi.2021.707466] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 08/04/2021] [Indexed: 12/31/2022] Open
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease with complex pathological characteristics, whose etiology and pathogenesis are still unclear. Over the past few decades, the role of the extracellular matrix (ECM) has gained importance in neurodegenerative disease. In this review, we describe the role of the ECM in AD, focusing on the aspects of synaptic transmission, amyloid-β-plaque generation and degradation, Tau-protein production, oxidative-stress response, and inflammatory response. The function of ECM in the pathological process of AD will inform future research on the etiology and pathogenesis of AD.
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Affiliation(s)
- Yahan Sun
- College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China
| | - Sen Xu
- College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China
| | - Ming Jiang
- College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China
| | - Xia Liu
- College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China
| | - Liang Yang
- College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China
| | - Zhantao Bai
- College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China
| | - Qinghu Yang
- College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China
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22
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Ru X, Gao L, Zhou J, Li Q, Zuo S, Chen Y, Liu Z, Feng H. Secondary White Matter Injury and Therapeutic Targets After Subarachnoid Hemorrhage. Front Neurol 2021; 12:659740. [PMID: 34335439 PMCID: PMC8319471 DOI: 10.3389/fneur.2021.659740] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 06/11/2021] [Indexed: 01/19/2023] Open
Abstract
Aneurysmal subarachnoid hemorrhage (SAH) is one of the special stroke subtypes with high mortality and mobility. Although the mortality of SAH has decreased by 50% over the past two decades due to advances in neurosurgery and management of neurocritical care, more than 70% of survivors suffer from varying degrees of neurological deficits and cognitive impairments, leaving a heavy burden on individuals, families, and the society. Recent studies have shown that white matter is vulnerable to SAH, and white matter injuries may be one of the causes of long-term neurological deficits caused by SAH. Attention has recently focused on the pivotal role of white matter injury in the pathophysiological processes after SAH, mainly related to mechanical damage caused by increased intracerebral pressure and the metabolic damage induced by blood degradation and hypoxia. In the present review, we sought to summarize the pathophysiology processes and mechanisms of white matter injury after SAH, with a view to providing new strategies for the prevention and treatment of long-term cognitive dysfunction after SAH.
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Affiliation(s)
- Xufang Ru
- State Key Laboratory of Trauma, Burn and Combined Injury, Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.,Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Ling Gao
- Department of General Practice, Audio-Visual Education Center, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jiru Zhou
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qiang Li
- State Key Laboratory of Trauma, Burn and Combined Injury, Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.,Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Shilun Zuo
- Department of Neurology, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yujie Chen
- State Key Laboratory of Trauma, Burn and Combined Injury, Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.,Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Zhi Liu
- State Key Laboratory of Trauma, Burn and Combined Injury, Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.,Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hua Feng
- State Key Laboratory of Trauma, Burn and Combined Injury, Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.,Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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23
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Jurcau A, Simion A. Cognition, Statins, and Cholesterol in Elderly Ischemic Stroke Patients: A Neurologist's Perspective. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:616. [PMID: 34199243 PMCID: PMC8231765 DOI: 10.3390/medicina57060616] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 05/28/2021] [Accepted: 06/09/2021] [Indexed: 12/25/2022]
Abstract
Background and Objectives: The efficacy of hydroxy methyl glutaryl-coenzyme A reductase inhibitors (statins) in reducing the incidence of cardiovascular events pushed the target LDL-cholesterol (LDL-C) levels lower and lower in successive guidelines despite signals regarding potential cognitive side effects. We evaluated the relationship between cognitive impairment and LDL-C levels in elderly ischemic stroke patients. Materials and Methods: 29 ischemic stroke patients aged 65 and above with LDL-C levels ≤70 mg/dL, classified according to the TOAST criteria, underwent detailed neuropsychological testing comprising the MMSE test, Montreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Evaluation (ACE-III) test. Their performances were compared to those of 29 age-matched ischemic stroke patients with LDL-Cl levels >71 mg/dL. Results: The MMSE test failed to detect significant cognitive differences between the two groups. The MoCA and ACE-III tests detected impairments in visuo-spatial/executive function, attention, and recall/memory in patients with low LDL-C. A stepwise linear regression model of the ACE-III total scores revealed that LDL-cholesterol levels could contribute to 13.8% of the detected cognitive dysfunction, second in importance only to age, which contributed to 38.8% of the detected impairment. Conclusions: Physicians should be cautious when prescribing statins to elderly people. Hydrophilic ones may be preferred in cognitively impaired patients.
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Affiliation(s)
- Anamaria Jurcau
- Department of Psycho-Neurosciences and Rehabilitation, Faculty of Medicine and Pharmacy, University of Oradea, nr 1 Universitatii Street, 410087 Oradea, Romania;
- Neurology Ward, Clinical Municipal Hospital “dr. G. Curteanu”, nr 12 Corneliu Coposu Street, 410469 Oradea, Romania
| | - Aurel Simion
- Department of Psycho-Neurosciences and Rehabilitation, Faculty of Medicine and Pharmacy, University of Oradea, nr 1 Universitatii Street, 410087 Oradea, Romania;
- Neurological Rehabilitation Ward, Clinical Municipal Hospital “dr. G. Curteanu”, nr 12 Corneliu Coposu Street, 410469 Oradea, Romania
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24
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Yi C, Zhang W, Ye H, Wu H, Huang X, Lin J, Yang X. Association of brachial-ankle pulse wave velocity with cognitive impairment in peritoneal dialysis patients. Ren Fail 2021; 43:934-941. [PMID: 34120562 PMCID: PMC8205036 DOI: 10.1080/0886022x.2021.1937221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background The relationship between cognitive impairment (CI) and arterial stiffness in peritoneal dialysis (PD) patients has not been clearly clarified. The aim of this study was to examine the relationship between CI and arterial stiffness in PD patients. Methods This cross-sectional study enrolled PD patients who performed a vascular profiler test at a single PD center in China between January 2014 and June 2016. The cognitive function was evaluated using the Montreal cognitive assessment (MoCA). A noninvasive vascular screening device was used to assess arterial stiffness relevant indicators. Results A total of 643 PD patients with median age 45 (37–57.4) years and median duration of PD 27.8 (8.7–56.4) months were enrolled. The rate of CI was 49.9%. The mean brachial-ankle pulse wave velocity (baPWV) was 17.2 ± 5.6 m/s. Compared with normal cognitive function group, patients with CI had higher baPWV (18.6 ± 7.0 vs. 15.8 ± 3.2 m/s), systolic blood pressure (150.3 ± 21.5 vs. 144.2 ± 20.2 mmHg), and pulse pressure (59.7 ± 14.7 vs. 52.5 ± 11.6 mmHg), and lower ankle-brachial index (ABI, 1.12 ± 0.12 vs. 1.15 ± 0.09) (all p<.05). Compared with systolic blood pressure, pulse pressure, and ABI in receiver operating characteristic (ROC) analysis, baPWV had better performance in predicting CI (area under curve: 0.68, 95% confidence interval: 0.64–0.72). BaPWV was independently associated with MoCA score (B per SD, −0.42 [95% confidence interval, −0.71 to −0.12]; p = .006) and CI (OR per SD, 1.55 [95% confidence interval, 1.11–2.17]; p = .011) in PD patients after adjustment for confounders. Conclusions Higher baPWV was independently associated with CI in PD patients.
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Affiliation(s)
- Chunyan Yi
- Department of Nephrology,The First Affiliated Hospital, Sun Yat-sen University and Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, PR China
| | - Wenbo Zhang
- Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China
| | - Hongjian Ye
- Department of Nephrology,The First Affiliated Hospital, Sun Yat-sen University and Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, PR China
| | - Haishan Wu
- Department of Nephrology,The First Affiliated Hospital, Sun Yat-sen University and Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, PR China
| | - Xuan Huang
- Department of Nephrology,The First Affiliated Hospital, Sun Yat-sen University and Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, PR China
| | - Jianxiong Lin
- Department of Nephrology,The First Affiliated Hospital, Sun Yat-sen University and Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, PR China
| | - Xiao Yang
- Department of Nephrology,The First Affiliated Hospital, Sun Yat-sen University and Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, PR China
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25
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Kanamaru T, Suda S, Muraga K, Ishiwata A, Aoki J, Suzuki K, Sakamoto Y, Katano T, Nishimura T, Nishiyama Y, Kimura K. Pre-stroke cognitive impairment in acute ischemic stroke patients predicts poor functional outcome after mechanical thrombectomy. Neurol Sci 2021; 42:4629-4635. [PMID: 33666769 DOI: 10.1007/s10072-021-05158-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/27/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Several studies have investigated the predictors of functional outcome in patients with ischemic stroke after mechanical thrombectomy (MT). However, it is not clear whether pre-stroke cognitive (PSC) impairment is associated with the functional outcome of patients treated with MT. METHODS We enrolled 113 patients treated with MT from December 2016 to November 2018. PSC was evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Poor outcome was defined as a modified Rankin Scale score of 3-6. We compared the clinical characteristics between the groups with poor outcome (n = 61) and good outcome (n = 52) to determine if PSC could be a predictor of poor outcome. RESULTS IQCODE was significantly higher in the group with poor outcome than good outcome (3.34 vs. 3.13, P = 0.017). Moreover, the following metrics differed between those two groups: age (75.9 vs. 71.6 years old, P = 0.010), the percentage of females (39.9% vs. 17.3%, P = 0.009), the percentage with hypertension (72.1% vs. 44.2%, P = 0.003), National Institutes of Health Stroke Scale (NIHSS) score on admission (20 vs. 11, P < 0.001), and no successful recanalization (24.5% vs. 7.7%; P = 0.025). Multivariable logistic regression analysis demonstrated that PSC (OR: 5.59; 95% CI: 1.55-23.47), history of hypertension (OR: 3.33; 95% CI: 1.29-9.11), no successful recanalization (OR: 5.51; 95% CI: 1.49-25.03), and NIHSS score on admission (OR: 1.14; 95% CI: 1.07-1.22) were associated with poor outcome 3 months after stroke onset. CONCLUSIONS PSC was significantly and independently associated with poor functional outcome in patients treated with MT.
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Affiliation(s)
- Takuya Kanamaru
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
| | - Satoshi Suda
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Kanako Muraga
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Akiko Ishiwata
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Junya Aoki
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Kentaro Suzuki
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Yuki Sakamoto
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Takehiro Katano
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Takuya Nishimura
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Yasuhiro Nishiyama
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Kazumi Kimura
- Department of Neurology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
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26
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Klein AP, Yarbrough K, Cole JW. Stroke, Smoking and Vaping: The No-Good, the Bad and the Ugly. ANNALS OF PUBLIC HEALTH AND RESEARCH 2021; 8:1104. [PMID: 34322688 PMCID: PMC8315328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Both stroke and smoking continue to be major public health crises in the United States, with stroke being the third and fourth leading cause of death among women and men, respectively. The goal of this review will be to provide clinicians a succinct overview regarding the epidemiology, economics, and biology of stroke in the setting of smoking and electronic cigarette use. Special attention will be given to the escalating public health crisis of electronic cigarette use, emphasizing mechanistic relationships of stroke and lung injury. Readers will be made aware of the need for continued scientific advancement and study regarding these relationships, as well as the need for improved governmental and public health efforts to curb these ongoing public health crises.
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Affiliation(s)
- Adam P Klein
- Department of Neurology, University of Maryland School of Medicine, USA
| | - Karen Yarbrough
- Department of Neurology, University of Maryland School of Medicine, USA
| | - John W Cole
- Department of Neurology, Veterans Affairs Maryland Health Care System and the University of Maryland School of Medicine, USA
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27
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Czakó C, Kovács T, Ungvari Z, Csiszar A, Yabluchanskiy A, Conley S, Csipo T, Lipecz A, Horváth H, Sándor GL, István L, Logan T, Nagy ZZ, Kovács I. Retinal biomarkers for Alzheimer's disease and vascular cognitive impairment and dementia (VCID): implication for early diagnosis and prognosis. GeroScience 2020; 42:1499-1525. [PMID: 33011937 PMCID: PMC7732888 DOI: 10.1007/s11357-020-00252-7] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 08/10/2020] [Indexed: 12/11/2022] Open
Abstract
Cognitive impairment and dementia are major medical, social, and economic public health issues worldwide with significant implications for life quality in older adults. The leading causes are Alzheimer's disease (AD) and vascular cognitive impairment/dementia (VCID). In both conditions, pathological alterations of the cerebral microcirculation play a critical pathogenic role. Currently, the main pathological biomarkers of AD-β-amyloid peptide and hyperphosphorylated tau proteins-are detected either through cerebrospinal fluid (CSF) or PET examination. Nevertheless, given that they are invasive and expensive procedures, their availability is limited. Being part of the central nervous system, the retina offers a unique and easy method to study both neurodegenerative disorders and cerebral small vessel diseases in vivo. Over the past few decades, a number of novel approaches in retinal imaging have been developed that may allow physicians and researchers to gain insights into the genesis and progression of cerebromicrovascular pathologies. Optical coherence tomography (OCT), OCT angiography, fundus photography, and dynamic vessel analyzer (DVA) are new imaging methods providing quantitative assessment of retinal structural and vascular indicators-such as thickness of the inner retinal layers, retinal vessel density, foveal avascular zone area, tortuosity and fractal dimension of retinal vessels, and microvascular dysfunction-for cognitive impairment and dementia. Should further studies need to be conducted, these retinal alterations may prove to be useful biomarkers for screening and monitoring dementia progression in clinical routine. In this review, we seek to highlight recent findings and current knowledge regarding the application of retinal biomarkers in dementia assessment.
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Affiliation(s)
- Cecilia Czakó
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Tibor Kovács
- Department of Neurology, Semmelweis University, Budapest, Hungary
| | - Zoltan Ungvari
- Translational Geroscience Laboratory, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
- International Training Program in Geroscience, Theoretical Medicine Doctoral School/Departments of Medical Physics and Informatics & Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Anna Csiszar
- Translational Geroscience Laboratory, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Theoretical Medicine Doctoral School/Departments of Medical Physics and Informatics & Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary
| | - Andriy Yabluchanskiy
- Translational Geroscience Laboratory, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Shannon Conley
- Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Tamas Csipo
- Translational Geroscience Laboratory, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Agnes Lipecz
- Translational Geroscience Laboratory, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Vascular Cognitive Impairment and Neurodegeneration Program, Center for Geroscience and Healthy Brain Aging/Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Ophthalmology, Josa Andras Hospital, Nyiregyhaza, Hungary
| | - Hajnalka Horváth
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | | | - Lilla István
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Trevor Logan
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Zoltán Zsolt Nagy
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Illés Kovács
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
- Department of Ophthalmology, Weill Cornell Medical College, New York City, NY, USA.
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28
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Nyúl-Tóth Á, Tarantini S, Kiss T, Toth P, Galvan V, Tarantini A, Yabluchanskiy A, Csiszar A, Ungvari Z. Increases in hypertension-induced cerebral microhemorrhages exacerbate gait dysfunction in a mouse model of Alzheimer's disease. GeroScience 2020; 42:1685-1698. [PMID: 32844283 PMCID: PMC7732885 DOI: 10.1007/s11357-020-00256-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/17/2020] [Indexed: 12/17/2022] Open
Abstract
Clinical studies show that cerebral amyloid angiopathy (CAA) associated with Alzheimer's disease (AD) and arterial hypertension are independent risk factors for cerebral microhemorrhages (CMHs). To test the hypothesis that amyloid pathology and hypertension interact to promote the development of CMHs, we induced hypertension in the Tg2576 mouse model of AD and respective controls by treatment with angiotensin II (Ang II) and the NO synthesis inhibitor L-NAME. The number, size, localization, and neurological consequences (gait alterations) of CMHs were compared. We found that compared to control mice, in TG2576 mice, the same level of hypertension led to significantly increased CMH burden and exacerbation of CMH-related gait alterations. In hypertensive TG2576 mice, CMHs were predominantly located in the cerebral cortex at the cortical-subcortical boundary, mimicking the clinical picture seen in patients with CAA. Collectively, amyloid pathologies exacerbate the effects of hypertension, promoting the genesis of CMHs, which likely contribute to their deleterious effects on cognitive function. Therapeutic strategies for prevention of CMHs that reduce blood pressure and preserve microvascular integrity are expected to exert neuroprotective effects in high-risk elderly AD patients.
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Affiliation(s)
- Ádám Nyúl-Tóth
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Institute of Biophysics, Biological Research Centre, Szeged, Hungary
| | - Stefano Tarantini
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Tamas Kiss
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Theoretical Medicine Doctoral School/Departments of Medical Physics and Informatics & Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary
| | - Peter Toth
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
- International Training Program in Geroscience, Doctoral School of Clinical Medicine, Department of Neurosurgery and Szentagothai Research Center, Medical School, University of Pecs, Pecs, Hungary
| | - Veronica Galvan
- Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- South Texas Veterans Health Care System, San Antonio, TX, USA
- Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | - Amber Tarantini
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
| | - Andriy Yabluchanskiy
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Anna Csiszar
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Theoretical Medicine Doctoral School/Departments of Medical Physics and Informatics & Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary
| | - Zoltan Ungvari
- Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary.
- International Training Program in Geroscience, Theoretical Medicine Doctoral School/Departments of Medical Physics and Informatics & Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary.
- Department of Biochemistry and Molecular Biology, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA.
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29
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Time-dependent effects of platelet-rich plasma on the memory and hippocampal synaptic plasticity impairment in vascular dementia induced by chronic cerebral hypoperfusion. Brain Res Bull 2020; 164:299-306. [DOI: 10.1016/j.brainresbull.2020.08.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 08/19/2020] [Accepted: 08/30/2020] [Indexed: 12/19/2022]
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30
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McKinnon AC, Stickel A, Ryan L. Cardiovascular risk factors and APOE-ε4 status affect memory functioning in aging via changes to temporal stem diffusion. J Neurosci Res 2020; 99:502-517. [PMID: 33070365 DOI: 10.1002/jnr.24734] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/28/2020] [Accepted: 09/02/2020] [Indexed: 01/08/2023]
Abstract
Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age-related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE-ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion-weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE-ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.
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Affiliation(s)
- Andrew C McKinnon
- Cognition and Neuroimaging Laboratory, Department of Psychology, University of Arizona, Tucson, AZ, USA.,Healthy Brain Ageing Program, School of Psychology, University of Sydney, Sydney, NSW, Australia.,Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia
| | - Ariana Stickel
- Cognition and Neuroimaging Laboratory, Department of Psychology, University of Arizona, Tucson, AZ, USA.,Department of Neurosciences, University of California, San Diego, CA, USA
| | - Lee Ryan
- Cognition and Neuroimaging Laboratory, Department of Psychology, University of Arizona, Tucson, AZ, USA
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31
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Lubart A, Benbenishty A, Har-Gil H, Laufer H, Gdalyahu A, Assaf Y, Blinder P. Single Cortical Microinfarcts Lead to Widespread Microglia/Macrophage Migration Along the White Matter. Cereb Cortex 2020; 31:248-266. [PMID: 32954425 DOI: 10.1093/cercor/bhaa223] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Revised: 05/13/2020] [Accepted: 06/08/2020] [Indexed: 12/31/2022] Open
Abstract
Loss of cognitive function with aging is a complex and poorly understood process. Recently, clinical research has linked the occurrence of cortical microinfarcts to cognitive decline. Cortical microinfarcts form following the occlusion of penetrating vessels and are considered to be restricted to the proximity of the occluded vessel. Whether and how such local events propagate and affect remote brain regions remain unknown. To this end, we combined histological analysis and longitudinal diffusion tensor imaging (DTI), following the targeted-photothrombotic occlusion of single cortical penetrating vessels. Occlusions resulted in distant tissue reorganization across the mouse brain. This remodeling co-occurred with the formation of a microglia/macrophage migratory path along subcortical white matter tracts, reaching the contralateral hemisphere through the corpus callosum and leaving a microstructural signature detected by DTI-tractography. CX3CR1-deficient mice exhibited shorter trail lengths, differential remodeling, and only ipsilateral white matter tract changes. We concluded that microinfarcts lead to brain-wide remodeling in a microglial CX3CR1-dependent manner.
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Affiliation(s)
- Alisa Lubart
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel
| | - Amit Benbenishty
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel.,Biological Regulation Department, The Weizmann Institute of Science, Rehovot, Israel
| | - Hagai Har-Gil
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel
| | - Hadas Laufer
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel
| | - Amos Gdalyahu
- Neurobiology, Biochemistry and Biophysics School, Tel Aviv University, Tel Aviv-Yafo, Israel
| | - Yaniv Assaf
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel.,Neurobiology, Biochemistry and Biophysics School, Tel Aviv University, Tel Aviv-Yafo, Israel
| | - Pablo Blinder
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv-Yafo, Israel.,Neurobiology, Biochemistry and Biophysics School, Tel Aviv University, Tel Aviv-Yafo, Israel
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32
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Araghi M, Shipley MJ, Wilkinson IB, McEniery CM, Valencia-Hernández CA, Kivimaki M, Sabia S, Singh-Manoux A, Brunner EJ. Association of aortic stiffness with cognitive decline: Whitehall II longitudinal cohort study. Eur J Epidemiol 2020; 35:861-869. [PMID: 31776832 PMCID: PMC7441227 DOI: 10.1007/s10654-019-00586-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 11/13/2019] [Indexed: 12/14/2022]
Abstract
Aortic stiffness is associated with an increased risk of cardio- and cerebrovascular disease and mortality and may increase risk of dementia. The aim of the present study is to examine the association between arterial stiffness and cognitive decline in a large prospective cohort study with three repeated cognitive assessment over 7 years of follow-up. Aortic pulse wave velocity (PWV) was measured among 4300 participants (mean ± standard deviation age 65.1 ± 5.2 years) in 2007-2009 and categorized based on the tertiles: (lowest third: < 7.41 m/s), (middle third: 7.41-8.91 m/s), and (highest third: > 8.91 m/s). A global cognitive score was calculated in 2007-2009, 2012-2013, and 2015-2016 based on responses to memory, reasoning and fluency tests. Standardized global cognitive score (mean = 0, SD = 1) in highest third versus lowest third of PWV category was lower at baseline (- 0.12, 95% CI - 0.18, - 0.06). Accelerated 7-year cognitive decline was observed among individuals with the highest PWV [difference in 7-year cognitive change for highest third versus lowest third PWV: - 0.06, 95% CI - 0.11, - 0.01, P < 0.01]. Higher aortic stiffness was associated with faster cognitive decline. Clinicians may be able to use arterial stiffness severity as an indicator to administer prompt treatments to prevent or delay the onset of cognitive decline or dementia. Future studies need to determine whether early intervention of vascular stiffness is effective in delaying these outcomes.
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Affiliation(s)
- Marzieh Araghi
- Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK.
| | - Martin J Shipley
- Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK
| | - Ian B Wilkinson
- Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK
| | - Carmel M McEniery
- Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK
| | - Carlos A Valencia-Hernández
- Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK
| | - Mika Kivimaki
- Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK
| | - Séverine Sabia
- Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK
- Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases, Paris, France
| | - Archana Singh-Manoux
- Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK
- Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases, Paris, France
| | - Eric J Brunner
- Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, WC1E 6BT, UK
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33
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Taneja K, Liu P, Xu C, Turner M, Zhao Y, Abdelkarim D, Thomas BP, Rypma B, Lu H. Quantitative Cerebrovascular Reactivity in Normal Aging: Comparison Between Phase-Contrast and Arterial Spin Labeling MRI. Front Neurol 2020; 11:758. [PMID: 32849217 PMCID: PMC7411174 DOI: 10.3389/fneur.2020.00758] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 06/19/2020] [Indexed: 12/20/2022] Open
Abstract
Purpose: Cerebrovascular reactivity (CVR) is an index of the dilatory function of cerebral blood vessels and has shown great promise in the diagnosis of risk factors in cerebrovascular disease. Aging is one such risk factor; thus, it is important to characterize age-related differences in CVR. CVR can be measured by BOLD MRI but few studies have measured quantitative cerebral blood flow (CBF)-based CVR in the context of aging. This study aims to determine the age effect on CVR using two quantitative CBF techniques, phase-contrast (PC), and arterial spin labeling (ASL) MRI. Methods: In 49 participants (32 younger and 17 older), CVR was measured with PC, ASL, and BOLD MRI. These CVR methods were compared across young and older groups to determine their dependence on age. PC and ASL CVR were also studied for inter-correlation and mean differences. Gray and white matter CVR values were also studied. Results: PC CVR was higher in younger participants than older participants (by 17%, p = 0.046). However, there were no age differences in ASL or BOLD CVR. ASL CVR was significantly correlated with PC CVR (p = 0.042) and BOLD CVR (p = 0.016), but its values were underestimated compared to PC CVR (p = 0.045). ASL CVR map revealed no difference between gray matter and white matter tissue types, whereas gray matter was significantly higher than white matter in the BOLD CVR map. Conclusion: This study compared two quantitative CVR techniques in the context of brain aging and revealed that PC CVR is a more sensitive method for detection of age differences, despite the absence of spatial information. The ASL method showed a significant correlation with PC and BOLD, but it tends to underestimate CVR due to confounding factors associated with this technique. Importantly, our data suggest that there is not a difference in CBF-based CVR between the gray and white matter, in contrast to previous observation using BOLD MRI.
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Affiliation(s)
- Kamil Taneja
- The Russel H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Peiying Liu
- The Russel H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Cuimei Xu
- The Russel H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Monroe Turner
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States
| | - Yuguang Zhao
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States
| | - Dema Abdelkarim
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States
| | - Binu P Thomas
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Bart Rypma
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, United States.,Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Hanzhang Lu
- The Russel H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.,F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States.,Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States
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Song MK, Kim YJ, Lee JM, Kim YJ. Neurovascular integrative effects of long-term environmental enrichment on chronic cerebral hypoperfusion rat model. Brain Res Bull 2020; 163:160-169. [PMID: 32711044 DOI: 10.1016/j.brainresbull.2020.07.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 07/02/2020] [Accepted: 07/20/2020] [Indexed: 12/11/2022]
Abstract
Vascular dementia (VaD) is one of the most common types of dementia followed by Alzheimer's disease (AD). Recent studies showed that approximately 30 %-35 % of patients with AD at post-mortem exhibited vascular pathologies, which suggested that mixed dementia may be the most common type of dementia. Permanent bilateral common carotid artery occlusion (2VO) is a well-characterized method for investigating cognitive functions and the histopathological consequences of chronic cerebral hypoperfusion (CCH) in rats. In the present study, we investigated the effects of environmental enrichment (EE) on cognitive impairment after CCH, as well as the effects of CCH-induced neurovascular damage on cognitive function. Wistar rats were randomly allocated to a sham group, a 2VO group, and a 2VO + EE group. The 2VO procedure was performed at 12 weeks, while EE was performed for 8 weeks before and 6 weeks after 2VO. The effect of EE on cognitive functions in 2VO rats was investigated using the radial-arm maze and Morris Water Maze tests. Neurovascular integrity was assessed based on immunoreactivity for glial fibrillary acidic protein (GFAP), morphological changes in microvessels, and the expression of matrix metalloproteinase-9 (MMP-9) and zonula occludens-1 (ZO-1) in the motor cortex and hippocampus. EE ameliorated microvessel fragmentation by sustaining the tight junction through increases of ZO-1 expression after CCH, resulting in preserving the neurovascular unit. In summary, EE mitigated cognitive impairment by restoring neurovascular integrity. These findings suggest that EE can be a valuable and meaningful environmental intervention for patients with cognitive impairment.
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Affiliation(s)
- Min Kyung Song
- Department of Nursing, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Yoon Ju Kim
- Department of Nursing, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Jae-Min Lee
- Department of Nursing, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Youn-Jung Kim
- College of Nursing Science, Kyung Hee University, East-west Nursing Research Institute, Seoul, 02447, Republic of Korea.
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Shenmayizhi Formula Combined with Ginkgo Extract Tablets for the Treatment of Vascular Dementia: A Randomized, Double-Blind, Controlled Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:8312347. [PMID: 32774430 PMCID: PMC7397431 DOI: 10.1155/2020/8312347] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 06/22/2020] [Indexed: 01/05/2023]
Abstract
Shenmayizhi formula (SMYZF) has been shown to have an effect on vascular dementia (VaD) in previous studies. The aim of this study was to evaluate whether a combination of SMYZF with Ginkgo extract tablets improves mild-to-moderate VaD. In this 12-week, randomized, double-blind, controlled study, we randomly assigned 196 patients with VaD (aged 50-85 years) to either the SMYZF group (n = 98) or the Ginkgo group (n = 98). All patients received Ginkgo extract tablets as a basic treatment, while the SMYZF group also received SMYZF treatment. We evaluated the participants at baseline and after 12 weeks of the intervention for the following: the Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL), Chinese Medicine Symptom Scale (CM-SS) scores, serum endothelin-1 (ET-1), nitric oxide (NO), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), and homocysteine (Hcy) serum levels. Both interventions significantly increased MMSE scores and decreased NIHSS, ADL, and CM-SS scores. The SMYZF group showed greater improvement in MMSE, NIHSS, and CM-SS scores. Both groups showed a significant decrease in serum ET-1 and an increase in serum VEGF. Furthermore, serum NO increased, and vWF decreased significantly in the SMYZF group. Changes in serum ET-1 and NO were greater in the SMYZF group. Both groups showed a significant increase in serum BDNF and a decrease in serum NSE and Hcy. Improvement in serum NSE and BDNF was greater in the SMYZF group. SMYZF combined with Ginkgo extract tablets improved vascular endothelial and cognitive functions, as well as the syndromes diagnosed based on the traditional Chinese medicine in patients with VaD.
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Huang J, Tang J, Zhang Y, Zhang J, Tan Z, Shi S. Association between Ankle Brachial Index, Brachial-Ankle Pulse Wave Velocity, and Mild Cognitive Impairment in Patients with Acute Lacunar Infarction. Eur Neurol 2020; 83:147-153. [PMID: 32570253 DOI: 10.1159/000504844] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 11/15/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND The link between arterial stiffness and mild cognitive impairment (MCI) is receiving increasing attention, and the goal of this study was to explore the relationship among the ankle brachial index (ABI), brachial-ankle pulse wave velocity (Ba-PWV), and MCI in patients with acute lacunar infarction (ALI). METHODS A total of 103 hospitalized patients with ALI were divided into a non-MCI group (n = 41) and an MCI group (n = 62) according to their Montreal Cognitive Assessment (MoCA) scores. A binary logistic regression model was used to assess the association among ABI, Ba-PWV, and MCI after adjusting for confounding factors. Spearman correlation was utilized to analyse the correlations between ABI, Ba-PWV, and MoCA total scores and sub-scores in ALI patients. RESULTS Participants with cognitive impairment had significantly higher Ba-PWV and lower ABI than those with normal cognition. Correlation analysis suggested that Ba-PWV (r = -0.854, p < 0.05) and ABI (r = 0.734, p < 0.05) were correlated with MoCA total scores; of all MoCA sub-scores, visuospatial/executive function was the most strongly correlated with the vascular variables. In the binary logistic regression analysis, Ba-PWV (odds ratio [OR] = 4.507, 95% confidence interval [CI] = 2.152-9.441) and ABI (OR = 1.124, 95% CI = 1.015-1.254) were significantly associated with MCI, even after adjusting for lipoprotein (a) and systolic and diastolic blood pressure. CONCLUSION The present study suggested that a higher Ba-PWV and a lower ABI were independent risk factors for MCI in patients with ALI.
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Affiliation(s)
- Junling Huang
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jian Tang
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yueling Zhang
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jian Zhang
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhong Tan
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Shengliang Shi
- Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China,
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Leira Y, Carballo Á, Orlandi M, Aldrey JM, Pías‐Peleteiro JM, Moreno F, Vázquez‐Vázquez L, Campos F, D’Aiuto F, Castillo J, Sobrino T, Blanco J. Periodontitis and systemic markers of neurodegeneration: A case–control study. J Clin Periodontol 2020; 47:561-571. [DOI: 10.1111/jcpe.13267] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 12/28/2019] [Accepted: 02/03/2020] [Indexed: 01/08/2023]
Affiliation(s)
- Yago Leira
- Periodontology Unit UCL Eastman Dental Institute and NIHR UCLH Biomedical Research Centre University College London London UK
- Periodontology Unit Faculty of Medicine and Odontology University of Santiago de Compostela Santiago de Compostela Spain
- Medical‐Surgical Dentistry (OMEQUI) Research Group Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
| | - Álvaro Carballo
- Periodontology Unit Faculty of Medicine and Odontology University of Santiago de Compostela Santiago de Compostela Spain
| | - Marco Orlandi
- Periodontology Unit UCL Eastman Dental Institute and NIHR UCLH Biomedical Research Centre University College London London UK
| | - José Manuel Aldrey
- Dementia Unit Department of Neurology Clinical University Hospital Santiago de Compostela Spain
- Clinical Neurosciences Research Laboratory Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
| | - Juan Manuel Pías‐Peleteiro
- Dementia Unit Department of Neurology Clinical University Hospital Santiago de Compostela Spain
- Clinical Neurosciences Research Laboratory Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
| | - Federico Moreno
- Periodontology Unit UCL Eastman Dental Institute and NIHR UCLH Biomedical Research Centre University College London London UK
| | - Laura Vázquez‐Vázquez
- Dementia Unit Department of Neurology Clinical University Hospital Santiago de Compostela Spain
- Clinical Neurosciences Research Laboratory Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
| | - Francisco Campos
- Clinical Neurosciences Research Laboratory Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
| | - Francesco D’Aiuto
- Periodontology Unit UCL Eastman Dental Institute and NIHR UCLH Biomedical Research Centre University College London London UK
| | - José Castillo
- Clinical Neurosciences Research Laboratory Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
| | - Tomás Sobrino
- Clinical Neurosciences Research Laboratory Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
| | - Juan Blanco
- Periodontology Unit Faculty of Medicine and Odontology University of Santiago de Compostela Santiago de Compostela Spain
- Medical‐Surgical Dentistry (OMEQUI) Research Group Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain
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Neurovascular unit dysregulation, white matter disease, and executive dysfunction: the shared triad of vascular cognitive impairment and Alzheimer disease. GeroScience 2020; 42:445-465. [PMID: 32002785 DOI: 10.1007/s11357-020-00164-6] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 01/22/2020] [Indexed: 01/07/2023] Open
Abstract
Executive dysfunction is the most important predictor for loss of independence in dementia. As executive function involves the coordination of distributed cerebral functions, executive function requires healthy white matter. However, white matter is highly vulnerable to cerebrovascular insults, with executive dysfunction being a core feature of vascular cognitive impairment (VCI). At the same time, cerebrovascular pathology, white matter disease, and executive dysfunction are all increasingly recognized as features of Alzheimer disease (AD). Recent studies have characterized the crucial role of glial cells in the pathological changes observed in both VCI and AD. In comorbid VCI and AD, the glial cells of the neurovascular unit (NVU) emerge as important therapeutic targets for the preservation of white matter integrity and executive function. Our synthesis from current research identifies dysregulation of the NVU, white matter disease, and executive dysfunction as a fundamental triad that is common to both VCI and AD. Further study of this triad will be critical for advancing the prevention and management of dementia.
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Iulita MF, Duchemin S, Vallerand D, Barhoumi T, Alvarez F, Istomine R, Laurent C, Youwakim J, Paradis P, Arbour N, Piccirillo CA, Schiffrin EL, Girouard H. CD4 + Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II-Induced Hypertension. J Am Heart Assoc 2020; 8:e009372. [PMID: 30572753 PMCID: PMC6405729 DOI: 10.1161/jaha.118.009372] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD4+CD25+) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate the cerebrovascular damage induced by hypertension is unknown. Methods and Results C57BL/6 mice were perfused with angiotensin II (Ang II; 1000 ng/kg per minute) for 14 days and adoptive transfer of 3×105CD4+CD25+ T cells was performed via 2 intravenous injections. Control mice received a sham surgery and PBS. Treg prevented Ang II‐induced neurovascular uncoupling (P<0.05) and endothelial impairment (P<0.05), evaluated by laser Doppler flowmetry in the somatosensory cortex. The neuroprotective effect of Treg was abolished when they were isolated from mice deficient in interleukin‐10. Administration of interleukin‐10 (60 ng/d) to hypertensive mice prevented Ang II‐induced neurovascular uncoupling (P<0.05). Treg adoptive transfer also diminished systemic inflammation induced by Ang II (P<0.05), examined with a peripheral blood cytokine array. Mice receiving Ang II + Treg exhibited reduced numbers of Iba‐1+ cells in the brain cortex (P<0.05) and hippocampus (P<0.001) compared with mice infused only with Ang II. Treg prevented the increase in cerebral superoxide radicals. Overall, these effects did not appear to be directly modulated by Treg accumulating in the brain parenchyma, because only a nonsignificant number of Treg were detected in brain. Instead, Treg penetrated peripheral tissues such as the kidney, inguinal lymph nodes, and the spleen. Conclusions Treg prevent impaired cerebrovascular responses in Ang II‐induced hypertension. The neuroprotective effects of Treg involve the modulation of inflammation in the brain and periphery.
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Affiliation(s)
- M Florencia Iulita
- 1 Department of Neurosciences Université de Montréal Montréal Canada.,2 Groupe de recherche sur le système nerveux central (GRSNC) Université de Montréal Montréal Canada
| | - Sonia Duchemin
- 4 Department of Pharmacology and Physiology Université de Montréal Montréal Canada
| | - Diane Vallerand
- 4 Department of Pharmacology and Physiology Université de Montréal Montréal Canada
| | - Tlili Barhoumi
- 5 Lady Davis Institute for Medical Research McGill University Montréal Canada
| | - Fernando Alvarez
- 6 Centre of Excellence in Translational Immunology Research Institute of McGill University Health Centre McGill University Montréal Canada.,7 Department of Microbiology and Immunology McGill University Montréal Canada
| | - Roman Istomine
- 6 Centre of Excellence in Translational Immunology Research Institute of McGill University Health Centre McGill University Montréal Canada.,7 Department of Microbiology and Immunology McGill University Montréal Canada
| | - Cyril Laurent
- 1 Department of Neurosciences Université de Montréal Montréal Canada.,3 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) Montréal Canada
| | - Jessica Youwakim
- 4 Department of Pharmacology and Physiology Université de Montréal Montréal Canada
| | - Pierre Paradis
- 5 Lady Davis Institute for Medical Research McGill University Montréal Canada
| | - Nathalie Arbour
- 1 Department of Neurosciences Université de Montréal Montréal Canada.,3 Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) Montréal Canada
| | - Ciriaco A Piccirillo
- 6 Centre of Excellence in Translational Immunology Research Institute of McGill University Health Centre McGill University Montréal Canada.,7 Department of Microbiology and Immunology McGill University Montréal Canada
| | - Ernesto L Schiffrin
- 5 Lady Davis Institute for Medical Research McGill University Montréal Canada.,8 Department of Medicine Sir Mortimer B. Davis-Jewish General Hospital McGill University Montréal Canada
| | - Hélène Girouard
- 2 Groupe de recherche sur le système nerveux central (GRSNC) Université de Montréal Montréal Canada.,4 Department of Pharmacology and Physiology Université de Montréal Montréal Canada.,9 Centre de recherche de l'Institut universitaire de gériatrie de Montréal Canada
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Yu Y, Luo X, Li C, Ding F, Wang M, Xie M, Yu Z, Ransom BR, Wang W. Microglial Hv1 proton channels promote white matter injuries after chronic hypoperfusion in mice. J Neurochem 2019; 152:350-367. [PMID: 31769505 DOI: 10.1111/jnc.14925] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 11/16/2019] [Accepted: 11/19/2019] [Indexed: 12/30/2022]
Abstract
Microglia are critical in damage/repair processes during ischemic white matter injury (WMI). Voltage-gated proton channel (Hv1) is expressed in microglia and contributes to nicotinamide adenine dinucleotide phosphate oxidase complex-dependent production of reactive oxygen species (ROS). Recent findings have shown that Hv1 is involved in regulating luminal pH of M1-polarized microglial phagosomes and inhibits endocytosis in microglia. We previously reported that Hv1 facilitated production of ROS and pro-inflammatory cytokines in microglia and enhanced damage to oligodendrocyte progenitor cells from oxygen and glucose deprivation. To investigate the role of Hv1 in hypoperfusion-induced WMI, we employed mice that were genetically devoid of Hv1 (Hv1-/- ), as well as a model of subcortical vascular dementia via bilateral common carotid artery stenosis. Integrity of myelin was assessed using immunofluorescent staining and transmission electron microscopy, while cognitive impairment was assessed using an eight-arm radial maze test. Hv1 deficiency was found to attenuate bilateral common carotid artery stenosis-induced disruption of white matter integrity and impairment of working memory. Immunofluorescent staining and western blotting were used to assay changes in oligodendrocytes, OPCs, and microglial polarization. Compared with that in wild-type (WT) mice, Hv1-/- mice exhibited reduced ROS generation, decreased pro-inflammatory cytokines production, and an M2-dominant rather than M1-dominant microglial polarization. Furthermore, Hv1-/- mice exhibited enhanced OPC proliferation and differentiation into oligodendrocytes. Results of mouse-derived microglia-OPC co-cultures suggested that PI3K/Akt signaling was involved in Hv1-deficiency-induced M2-type microglial polarization and concomitant OPC differentiation. These results suggest that microglial Hv1 is a promising therapeutic target for reducing ischemic WMI and cognitive impairment.
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Affiliation(s)
- Ying Yu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Luo
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chunyu Li
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fengfei Ding
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Minghuan Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Minjie Xie
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiyuan Yu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bruce R Ransom
- Department of Neurology, University of Washington School of Medicine HMC, Seattle, WA, USA
| | - Wei Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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41
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Heterogeneity of Astrocytes in Grey and White Matter. Neurochem Res 2019; 46:3-14. [PMID: 31797158 DOI: 10.1007/s11064-019-02926-x] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 11/21/2019] [Accepted: 11/28/2019] [Indexed: 02/07/2023]
Abstract
Astrocytes are a diverse and heterogeneous type of glial cells. The major task of grey and white matter areas in the brain are computation of information at neuronal synapses and propagation of action potentials along axons, respectively, resulting in diverse demands for astrocytes. Adapting their function to the requirements in the local environment, astrocytes differ in morphology, gene expression, metabolism, and many other properties. Here we review the differential properties of protoplasmic astrocytes of grey matter and fibrous astrocytes located in white matter in respect to glutamate and energy metabolism, to their function at the blood-brain interface and to coupling via gap junctions. Finally, we discuss how this astrocytic heterogeneity might contribute to the different susceptibility of grey and white matter to ischemic insults.
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42
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Caruso P, Signori R, Moretti R. Small vessel disease to subcortical dementia: a dynamic model, which interfaces aging, cholinergic dysregulation and the neurovascular unit. Vasc Health Risk Manag 2019; 15:259-281. [PMID: 31496716 PMCID: PMC6689673 DOI: 10.2147/vhrm.s190470] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 01/14/2019] [Indexed: 12/14/2022] Open
Abstract
Background Small vessels have the pivotal role for the brain’s autoregulation. The arteriosclerosis-dependent alteration of the brain perfusion is one of the major determinants in small vessel disease. Endothelium distress can potentiate the flow dysregulation and lead to subcortical vascular dementia (sVAD). sVAD increases morbidity and disability. Epidemiological studies have shown that sVAD shares with cerebrovascular disease most of the common risk factors. The molecular basis of this pathology remains controversial. Purpose To detect the possible mechanisms between small vessel disease and sVAD, giving a broad vision on the topic, including pathological aspects, clinical and laboratory findings, metabolic process and cholinergic dysfunction. Methods We searched MEDLINE using different search terms (“vascular dementia”, “subcortical vascular dementia”, “small vessel disease”, “cholinergic afferents”, etc). Publications were selected from the past 20 years. Searches were extended to Embase, Cochrane Library, and LILIACS databases. All searches were done from January 1, 1998 up to January 31, 2018. Results A total of 560 studies showed up, and appropriate studies were included. Associations between traditional vascular risk factors have been isolated. We remarked that SVD and white matter abnormalities are seen frequently with aging and also that vascular and endothelium changes are related with age; the changes can be accelerated by different vascular risk factors. Vascular function changes can be heavily influenced by genetic and epigenetic factors. Conclusion Small vessel disease and the related dementia are two pathologies that deserve attention for their relevance and impact in clinical practice. Hypertension might be a historical problem for SVD and SVAD, but low pressure might be even more dangerous; CBF regional selective decrease seems to be a critical factor for small vessel disease-related dementia. In those patients, endothelium damage is a super-imposed condition. Several issues are still debatable, and more research is needed.
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Affiliation(s)
- Paola Caruso
- Department of Medical, Surgical and Health Sciences, Neurology Clinic, University of Trieste, Trieste, Italy
| | - Riccardo Signori
- Department of Medical, Surgical and Health Sciences, Neurology Clinic, University of Trieste, Trieste, Italy
| | - Rita Moretti
- Department of Medical, Surgical and Health Sciences, Neurology Clinic, University of Trieste, Trieste, Italy
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Nazarian A, Arbeev KG, Yashkin AP, Kulminski AM. Genetic heterogeneity of Alzheimer's disease in subjects with and without hypertension. GeroScience 2019; 41:137-154. [PMID: 31055733 PMCID: PMC6544706 DOI: 10.1007/s11357-019-00071-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 04/25/2019] [Indexed: 01/01/2023] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder caused by the interplay of multiple genetic and non-genetic factors. Hypertension is one of the AD risk factors that has been linked to underlying pathological changes like senile plaques and neurofibrillary tangles formation as well as hippocampal atrophy. In this study, we investigated the differences in the genetic architecture of AD between hypertensive and non-hypertensive subjects in four independent cohorts. Our genome-wide association analyses revealed significant associations of 15 novel potentially AD-associated polymorphisms (P < 5E-06) that were located outside the chromosome 19q13 region and were significant either in hypertensive or non-hypertensive groups. The closest genes to 14 polymorphisms were not associated with AD at P < 5E-06 in previous genome-wide association studies (GWAS). Also, four of them were located within two chromosomal regions (i.e., 3q13.11 and 17q21.2) that were not associated with AD at P < 5E-06 before. In addition, 30 genes demonstrated evidence of group-specific associations with AD at the false discovery rates (FDR) < 0.05 in our gene-based and transcriptome-wide association analyses. The chromosomal regions corresponding to four genes (i.e., 2p13.1, 9p13.3, 17q12, and 18q21.1) were not associated with AD at P < 5E-06 in previous GWAS. These genes may serve as a list of prioritized candidates for future functional studies. Our pathway-enrichment analyses revealed the associations of 11 non-group-specific and four group-specific pathways with AD at FDR < 0.05. These findings provided novel insights into the potential genetic heterogeneity of AD among subjects with and without hypertension.
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Affiliation(s)
- Alireza Nazarian
- Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Erwin Mill Building, 2024 W. Main St., Durham, NC, 27705, USA.
| | - Konstantin G Arbeev
- Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Erwin Mill Building, 2024 W. Main St., Durham, NC, 27705, USA
| | - Arseniy P Yashkin
- Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Erwin Mill Building, 2024 W. Main St., Durham, NC, 27705, USA
| | - Alexander M Kulminski
- Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Erwin Mill Building, 2024 W. Main St., Durham, NC, 27705, USA.
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Metabolic syndrome alters relationships between cardiometabolic variables, cognition and white matter hyperintensity load. Sci Rep 2019; 9:4356. [PMID: 30867458 PMCID: PMC6416472 DOI: 10.1038/s41598-019-40630-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Accepted: 02/01/2019] [Indexed: 02/05/2023] Open
Abstract
Cardiometabolic risk factors influence white matter hyperintensity (WMH) development: in metabolic syndrome (MetS), higher WMH load is often reported but the relationships between specific cardiometabolic variables, WMH load and cognitive performance are uncertain. We investigated these in a Brazilian sample (aged 50–85) with (N = 61) and without (N = 103) MetS. Stepwise regression models identified effects of cardiometabolic and demographic variables on WMH load (from FLAIR MRI) and verbal recall performance. WMH volume was greater in MetS, but verbal recall performance was not impaired. Age showed the strongest relationship with WMH load. Across all participants, systolic blood pressure (SBP) and fasting blood glucose were also contributors, and WMH volume was negatively associated with verbal recall performance. In non-MetS, higher HbA1c, SBP, and number of MetS components were linked to poorer recall performance while higher triglyceride levels appeared to be protective. In MetS only, these relationships were absent but education exerted a strongly protective effect on recall performance. Thus, results support MetS as a construct: the clustering of cardiometabolic variables in MetS alters their individual relationships with cognition; instead, MetS is characterised by a greater reliance on cognitive reserve mechanisms. In non-MetS, strategies to control HbA1c and SBP should be prioritised as these have the largest impact on cognition.
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45
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Ostroumova OD, Chernyaeva MS. Antihypertension drugs in prevention of cognition disorder and dementia: focus on calcium channel blockers and diuretics. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2018. [DOI: 10.15829/1728-8800-2018-5-79-91] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Arterial hypertension is associated with elevated risk of cognition decline and vascular dementia development, as the Alzheimer disease development. Therefore, antihypertension therapy might be of preventive value. The review is focused on literary data that witness on, despite controversial, evidence of cerebroprotective action of the range of antihypertension medications. Especially, dihydropyridine calcium antagonists, diuretics and some blockers of renin-angiotensin-aldosterone system. These act not only via blood pressure decrease, but due to additional specific neuroprotective mechanisms. This makes it to consider calcium antagonists and diuretics as a major component of systemic hypertension management, incl. elderly and senile patients, aiming to prevent cognition decline and dementia of various types development.Nitrendipine, among the calcium channels antagonists, and indapamide among diuretics have acquired the broadest evidence that points on their cerebroprotective properties.
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Affiliation(s)
- O. D. Ostroumova
- Evdokimov Moscow State University of Medicine and Dentistry (MSUMD); Sechenov First Moscow State University of the Ministry of Health (the Sechenov University)
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Bergman I, Johansson K, Lundberg C. Five-year change scores in old age for six neuropsychological tests and normative data for the Useful Field of View (UFOV) test: The influence of physical health. J Clin Exp Neuropsychol 2018; 41:229-245. [PMID: 30332909 DOI: 10.1080/13803395.2018.1527292] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
INTRODUCTION Neuropsychological assessment of cognitive change over time is often conducted in clinical settings, but whether neuropsychological change scores are influenced by physical health has, as far as we know, not been examined previously. METHOD In a sample of 153 older Swedish adults (age range, 72-86 years), we evaluated the influence of common age-related diseases, terminal decline pathology, age, education, and gender, to provide (a) preliminary test-specific regression weights and 90% confidence intervals to assess significant change in performance after five years on tests of visual scanning, mental shifting, visual spatial ability, memory, reaction time, and selective attention, and (b) normative data for the Useful Field of View test (UFOV) from a single testing occasion. RESULTS Multiple regression analyses showed that test-retest changes were affected by physical health for mental shifting, visual spatial ability, memory, and reaction time, by age for mental shifting and visual reaction time, by education for visual spatial ability, and by Age × Education for auditory reaction time. Gender did not affect any of the change scores. The overall average of variance explained was 2.5%: up to 8.1% for physical health, 4.4% for age, and 3.6% for education. The UFOV scores were mostly influenced by age, but also by physical health and education. CONCLUSIONS The findings indicate that considering the influence of health on normative change scores in old age in addition to demographic factors leads to more accurate predictions of whether true change has occurred.
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Affiliation(s)
- Ingvar Bergman
- a Function Area Aging Health and Functioning , Karolinska University Hospital , Stockholm , Sweden.,b Traffic Medicine Centre , Karolinska University Hospital , Stockholm , Sweden
| | - Kurt Johansson
- b Traffic Medicine Centre , Karolinska University Hospital , Stockholm , Sweden.,c Theme Aging , Karolinska University Hospital , Stockholm , Sweden
| | - Catarina Lundberg
- a Function Area Aging Health and Functioning , Karolinska University Hospital , Stockholm , Sweden.,b Traffic Medicine Centre , Karolinska University Hospital , Stockholm , Sweden
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Xu M, Wang MM, Gao Y, Keep RF, Shi Y. The effect of age-related risk factors and comorbidities on white matter injury and repair after ischemic stroke. Neurobiol Dis 2018; 126:13-22. [PMID: 30017454 DOI: 10.1016/j.nbd.2018.07.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Revised: 06/17/2018] [Accepted: 07/10/2018] [Indexed: 02/06/2023] Open
Abstract
White matter injury is a crucial component of human stroke, but it has often been neglected in preclinical studies. Most human stroke is associated with one or more comorbidities, including aging, hypertension, diabetes and metabolic syndrome including hyperlipidemia. The purpose of this review is to examine how age and hypertension impact stroke-induced white matter injury as well as white matter repair in both human stroke and preclinical models. It is essential that comorbidities be examined in preclinical trials as they may impact translatability to the clinic. In addition, understanding how comorbidities impact white matter injury and repair may provide new therapeutic opportunities for patients with those conditions.
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Affiliation(s)
- Mingyue Xu
- Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA; State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
| | - Michael M Wang
- Departments of Neurology and Physiology, University of Michigan, Ann Arbor, MI 48109, USA; VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA
| | - Yanqin Gao
- State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
| | - Richard F Keep
- Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
| | - Yejie Shi
- Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
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Toth P, Tarantini S, Rutkai I, Ungvari Z. Assessment of endothelial function in leptomeningeal arterioles derived from patients with Alzheimer's disease and vascular cognitive impairment. Am J Physiol Heart Circ Physiol 2018; 315:H790-H793. [PMID: 29932773 DOI: 10.1152/ajpheart.00367.2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Peter Toth
- Department of Neurosurgery, Medical School, University of Pecs , Pecs , Hungary.,Institute for Translational Medicine, Medical School, University of Pecs , Pecs , Hungary.,MTA-PTE Clinical Neuroscience MR Research Group of the Hungarian Academy of Sciences , Pecs , Hungary.,Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma
| | - Stefano Tarantini
- Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma
| | - Ibolya Rutkai
- Department of Pharmacology, Tulane University, School of Medicine, New Orleans, Louisana
| | - Zoltan Ungvari
- Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma
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Catchlove SJ, Pipingas A, Hughes ME, Macpherson H. Magnetic resonance imaging for assessment of cerebrovascular reactivity and its relationship to cognition: a systematic review. BMC Neurosci 2018; 19:21. [PMID: 29649969 PMCID: PMC5898077 DOI: 10.1186/s12868-018-0421-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 03/27/2018] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Cerebrovascular reactivity (CVR) refers to the responsiveness of cerebral vasculature to vasoactive stimuli. CVR is an indicator of brain health and can be assessed using vasodilatory techniques and magnetic resonance imaging (MRI). Using such approaches, some researchers have explored the relationship between CVR and cognition; here we systematically review this work. RESULTS We extracted information pertaining to: (1) study location and design, participant characteristics, sample sizes, (2) design of vascular challenge, end-tidal CO 2 (etCO 2 ) concentrations (if applicable), (3) MRI protocol, (4) cognitive assessment, (5) CVR values, and outcomes of statistical analyses with cognitive tests. Five studies assessed participants with cognitive impairment compared to controls, one studied patients with multiple sclerosis with or without cognitive impairment compared to controls, one examined patients with moyamoya disease with or without cognitive impairment, two investigated patients with Type 2 diabetes mellitus (T2DM), and one was a cross-sectional study with younger and older healthy adults. Cognition was typically probed using the MMSE and tests of executive function, while a number of vasodilatory techniques were employed. CONCLUSION CVR was associated with cognition in six of ten studies, but heterogeneity of study samples, designs and vasodilatory methods may have a role in the inconsistent findings. We make recommendations for future research that includes use of a multi-domain cognitive assessment and standardised hypercapnic challenge with MRI.
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Affiliation(s)
- Sarah J. Catchlove
- Centre for Human Psychopharmacology, Swinburne University, Hawthorn, Australia
| | - Andrew Pipingas
- Centre for Human Psychopharmacology, Swinburne University, Hawthorn, Australia
| | - Matthew E. Hughes
- Centre for Mental Health, Swinburne University, Hawthorn, Australia
- Australian National Imaging Facility, St. Lucia, Australia
| | - Helen Macpherson
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, Australia
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Sokolova IB, Ryzhak GA, Khavinson VK. Functional Cumulation of the Influence of Vascular Peptide Bioregulator on Microcirculation in the Brain Cortex of Spontaneously Hypertensive Rats. ADVANCES IN GERONTOLOGY 2018. [DOI: 10.1134/s2079057018020170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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