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Medicine (Abingdon, England : UK Ed.) Sep 2020Stroke is a clinically defined syndrome of acute, focal neurological deficit attributed to vascular injury (infarction, haemorrhage) of the central nervous system.... (Review)
Review
Stroke is a clinically defined syndrome of acute, focal neurological deficit attributed to vascular injury (infarction, haemorrhage) of the central nervous system. Stroke is the second leading cause of death and disability worldwide. Stroke is not a single disease but can be caused by a wide range of risk factors, disease processes and mechanisms. Hypertension is the most important modifiable risk factor for stroke, although its contribution differs for different subtypes. Most (85%) strokes are ischaemic, predominantly caused by small vessel arteriolosclerosis, cardioembolism and large artery athero-thromboembolism. Ischaemic strokes in younger patients can result from a different spectrum of causes such as extracranial dissection. Approximately 15% of strokes worldwide are the result of intracerebral haemorrhage, which can be deep (basal ganglia, brainstem), cerebellar or lobar. Deep haemorrhages usually result from deep perforator (hypertensive) arteriopathy (arteriolosclerosis), while lobar haemorrhages are mainly caused by cerebral amyloid angiopathy or arteriolosclerosis. A minority (about 20%) of intracerebral haemorrhages are caused by macrovascular lesions (vascular malformations, aneurysms, cavernomas), venous sinus thrombosis or rarer causes; these are particularly important in young patients (<50 years). Knowledge of vascular and cerebral anatomy is important in localizing strokes and understanding their mechanisms. This guides rational acute management, investigation, and secondary prevention.
PubMed: 32837228
DOI: 10.1016/j.mpmed.2020.06.002 -
Continuum (Minneapolis, Minn.) Jun 2022This article gives a broad overview of vascular cognitive impairment and dementia, including epidemiology, pathophysiology, clinical approach, and management. Emphasis... (Review)
Review
PURPOSE OF REVIEW
This article gives a broad overview of vascular cognitive impairment and dementia, including epidemiology, pathophysiology, clinical approach, and management. Emphasis is placed on understanding the common underlying types of cerebrovascular disease (including atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy) and awareness of rare inherited cerebrovascular disorders.
RECENT FINDINGS
The pathophysiology of vascular cognitive impairment and dementia is heterogeneous, and the most recent diagnostic criteria for vascular cognitive impairment and dementia break down the diagnosis of major vascular dementia into four phenotypic categories, including subcortical ischemic vascular dementia, poststroke dementia, multi-infarct dementia, and mixed dementia. Control of cardiovascular risk factors, including management of midlife blood pressure, cholesterol, and blood sugars, remains the mainstay of prevention for vascular cognitive impairment and dementia. Cerebral amyloid angiopathy requires special consideration when it comes to risk factor management given the increased risk of spontaneous intracerebral hemorrhage. Recent trials suggest some improvement in global cognitive function in patients with vascular cognitive impairment and dementia with targeted cognitive rehabilitation.
SUMMARY
Thorough clinical evaluation and neuroimaging form the basis for diagnosis. As vascular cognitive impairment and dementia is the leading nondegenerative cause of dementia, identifying risk factors and optimizing their management is paramount. Once vascular brain injury has occurred, symptomatic management should be offered and secondary prevention pursued.
Topics: Alzheimer Disease; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Cognitive Dysfunction; Dementia, Vascular; Humans; Neuroimaging
PubMed: 35678401
DOI: 10.1212/CON.0000000000001124 -
International Journal of Stroke :... Jan 2023Cerebral small vessel disease (SVD) causes lacunar stroke and intracerebral hemorrhage, and is the most common pathology underlying vascular cognitive impairment.... (Review)
Review
Cerebral small vessel disease (SVD) causes lacunar stroke and intracerebral hemorrhage, and is the most common pathology underlying vascular cognitive impairment. Increasingly, the importance of other clinical features of SVD is being recognized including motor impairment, (vascular) parkinsonism, impaired balance, falls, and behavioral symptoms, such as depression, apathy, and personality change. Epidemiological data show a high prevalence of the characteristic magnetic resonance imaging (MRI) features of white matter hyperintensities and lacunar infarcts in community studies, and recent data suggest that it is also a major health burden in low- and middle-income countries. In this review, we cover advances in diagnosis, imaging, clinical presentations, pathogenesis, and treatment.The two most common pathologies underlying SVD are arteriolosclerosis caused by aging, hypertension, and other conventional vascular risk factors, and cerebral amyloid angiopathy (CAA) caused by vascular deposition of β-amyloid. We discuss the revised Boston criteria of CAA based on MRI features, which have been recently validated. Imaging is providing important insights into pathogenesis, including improved detection of tissue damage using diffusion tensor imaging (DTI) leading to its use to monitor progression and surrogate endpoints in clinical trials. Advanced MRI techniques can demonstrate functional or dynamic abnormalities of the blood vessels, while the high spatial resolution provided by ultrahigh field MRI at 7 T allows imaging of individual perforating arteries for the first time, and the measurement of flow velocity and pulsatility within these arteries. DTI and structural network analysis have highlighted the importance of network disruption in mediating the effect of different SVD pathologies in causing a number of symptoms, including cognitive impairment, apathy, and gait disturbance.Despite the public health importance of SVD, there are few proven treatments. We review the evidence for primary prevention, and recent data showing how intensive blood pressure lowering reduces white matter hyperintensities (WMH) progression and delays the onset of cognitive impairment. There are few treatments for secondary prevention, but a number of trials are currently evaluating novel treatment approaches. Recent advances have implicated molecular processes related to endothelial dysfunction, nitric oxide synthesis, blood-brain barrier integrity, maintenance and repair of the extracellular matrix, and inflammation. Novel treatment approaches are being developed to a number of these targets. Finally, we highlight the importance of large International collaborative initiatives in SVD to address important research questions and cover a number which have recently been established.
Topics: Humans; Diffusion Tensor Imaging; Stroke; Cerebral Small Vessel Diseases; Cognitive Dysfunction; Magnetic Resonance Imaging; Stroke, Lacunar; Cerebral Amyloid Angiopathy
PubMed: 36575578
DOI: 10.1177/17474930221144911 -
Cell Transplantation Dec 2018Cerebral small vessel disease (CSVD) is composed of several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain, and refers to... (Review)
Review
Cerebral small vessel disease (CSVD) is composed of several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain, and refers to several pathological processes and etiologies. Neuroimaging features of CSVD include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. The main clinical manifestations of CSVD include stroke, cognitive decline, dementia, psychiatric disorders, abnormal gait, and urinary incontinence. Currently, there are no specific preventive or therapeutic measures to improve this condition. In this review, we will discuss the pathophysiology, clinical aspects, neuroimaging, progress of research to treat and prevent CSVD and current treatment of this disease.
Topics: Arteriolosclerosis; Cerebral Amyloid Angiopathy; Cerebral Small Vessel Diseases; Humans; Magnetic Resonance Imaging; Platelet Aggregation Inhibitors; Stroke; Tissue Plasminogen Activator; White Matter
PubMed: 30251566
DOI: 10.1177/0963689718795148 -
Molecular Neurodegeneration Jul 2023Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large and small vessels and is a key driver of age-related... (Review)
Review
Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large and small vessels and is a key driver of age-related cognitive decline. Severe VCID includes post-stroke dementia, subcortical ischemic vascular dementia, multi-infarct dementia, and mixed dementia. While VCID is acknowledged as the second most common form of dementia after Alzheimer's disease (AD) accounting for 20% of dementia cases, VCID and AD frequently coexist. In VCID, cerebral small vessel disease (cSVD) often affects arterioles, capillaries, and venules, where arteriolosclerosis and cerebral amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent small subcortical infarcts, lacunes of presumed vascular origin, enlarged perivascular space, microbleeds, and brain atrophy are neuroimaging hallmarks of cSVD. The current primary approach to cSVD treatment is to control vascular risk factors such as hypertension, dyslipidemia, diabetes, and smoking. However, causal therapeutic strategies have not been established partly due to the heterogeneous pathogenesis of cSVD. In this review, we summarize the pathophysiology of cSVD and discuss the probable etiological pathways by focusing on hypoperfusion/hypoxia, blood-brain barriers (BBB) dysregulation, brain fluid drainage disturbances, and vascular inflammation to define potential diagnostic and therapeutic targets for cSVD.
Topics: Humans; Dementia, Vascular; Alzheimer Disease; Causality; Risk Factors; Cerebral Small Vessel Diseases
PubMed: 37434208
DOI: 10.1186/s13024-023-00640-5 -
Arteriosclerosis, Thrombosis, and... Aug 2019The notion of what qualifies as vascular dementia has varied greatly since the first mention of dementia after apoplexy in ancient literature. Current insight points... (Review)
Review
The notion of what qualifies as vascular dementia has varied greatly since the first mention of dementia after apoplexy in ancient literature. Current insight points towards a multifactorial cause of cognitive decline at old age, in which vascular components like atherosclerosis, arterio(lo)sclerosis, (micro)infarcts, and amyloid angiopathy play an important role alongside other markers of neurodegeneration. Cerebrovascular disease will be present in most individuals with dementia, but-just like other causes-rarely a cause on its own. The consequent limitations of nosology may be alleviated by addition of a vascular component to the recently introduced amyloid/tau/neurodegeneration etiological classification system for dementia. Meanwhile, risk of dementia is increased about 2-fold after stroke, and the prevention of (recurrent) stroke remains a cornerstone in the prevention of vascular dementia. Similarly, control of cardiovascular risk factors from middle age onwards is likely to have contributed to the reported decline in the age-specific incidence of dementia over the past decades. In conjunction with experimental studies, large-scale observational evidence from imaging, genomics, metabolomics, and alike will continue to improve our understanding of the underlying pathophysiological processes. To prevent ecological fallacies, such etiological studies in patients with dementia are best served by inclusion of subjects regardless of the presumed (single) cause of their disease.
Topics: Cerebrovascular Disorders; Dementia, Vascular; Humans; Risk Factors; Stroke
PubMed: 31294622
DOI: 10.1161/ATVBAHA.119.311908 -
Journal of the American Society of... Oct 2017Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level,... (Review)
Review
Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria.
Topics: Aging; Humans; Kidney
PubMed: 28790143
DOI: 10.1681/ASN.2017040421 -
Acta Neuropathologica Aug 2017Longitudinal clinical-pathological studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and... (Review)
Review
Longitudinal clinical-pathological studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and cerebrovascular disease pathologies) as important factors in the development of Alzheimer's disease (AD) and other forms of dementia. Older persons with AD pathology, often have concomitant cerebrovascular disease pathologies (macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy) as well as other concomitant neurodegenerative disease pathologies (Lewy bodies, TDP-43, hippocampal sclerosis). These additional pathologies lower the threshold for clinical diagnosis of AD. Many of these findings from pathologic studies, especially for CVD, have been confirmed using sophisticated neuroimaging technologies. In vivo biomarker studies are necessary to provide an understanding of specific pathologic contributions and time course relationships along the spectrum of accumulating pathologies. In this review, we provide a clinical-pathological perspective on the role of multiple brain pathologies in dementia followed by a review of the available clinical and biomarker data on some of the mixed pathologies.
Topics: Alzheimer Disease; Cerebrovascular Disorders; Cognition Disorders; Cohort Studies; Humans; Longitudinal Studies; Neuroimaging
PubMed: 28488154
DOI: 10.1007/s00401-017-1717-7 -
Acta Neuropathologica Jan 2021Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive... (Review)
Review
Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.
Topics: Aged; Aged, 80 and over; Animals; Arterioles; Brain; Cerebral Amyloid Angiopathy; Cognition Disorders; Humans; Intracranial Arteriosclerosis; Neuroimaging
PubMed: 33098484
DOI: 10.1007/s00401-020-02235-6 -
Jornal Vascular Brasileiro 2021Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are... (Review)
Review
Cardiovascular diseases are the main cause of death in contemporary times. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg's arteriosclerosis are terms that are often used interchangeably, but they refer to different vascular pathologies. The objective of this study is to review the concepts of atherosclerosis, atherosclerosis, arteriosclerosis and Monckeberg medial calcific sclerosis (MMCS). The term arteriosclerosis is more generic, meaning the stiffening and consequent loss of elasticity of the arterial wall, and encompasses the other terms. Atherosclerosis is an inflammatory disease secondary to lesions in the intimal layer and whose main complication is acute and chronic obstruction of the arterial lumen. Arteriolosclerosis refers to thickening of arterioles, particularly in association with systemic arterial hypertension. MMCS refers to non-obstructive calcification in the internal elastic lamina or the tunica media of muscular arteries. Vascular calcifications, which include atherosclerotic lesions and MMCS, have been studied as a risk factor for cardiovascular morbidity and mortality.
PubMed: 34290756
DOI: 10.1590/1677-5449.200211