Concept Of Vascular Cognitive Impairment Research Articles

Brain Health-Curbing Stroke, Heart Disease, and Dementia: The 2020 Wartenberg Lecture.

There is no health without brain health, which is threatened by rising curves of stroke, ischemic heart disease, and dementia (the triple threat). The fastest growing and intractable threat has been dementia. Focusing on finding a drug to stop Alzheimer disease has yielded growing knowledge but no treatments, partly because in the elderly, cognitive impairment results from multiple interactive pathologies aggravated by fragility and tempered by resilience on the advancing background of aging. The concept of vascular cognitive impairment (VCI) cuts pragmatically through this complexity. VCI is any cognitive impairment caused by or associated with vascular factors. It spans the spectrum of undetected cognitive impairment to full-blown dementia. The vascular component represents the only major current, treatable, and preventable contributor to dementia and offers the possibility of delaying, mitigating, or preventing more dementias in the near future. The triple threat conditions share the same protective and treatable risk factors and can be prevented together. The approach needs to be comprehensive, identifying all relevant environmental, socioeconomic, health care, and individual factors; targeted, as risks and protective factors differ among populations and individuals; and and investment valued, yielding worthwhile returns in terms of money, effort, or time. The World Stroke Organization's proclamation calling for the joint prevention of stroke and potentially preventable dementias has been endorsed by 23 international, regional, and national brain and heart organizations, including the American Academy of Neurology. We need to develop joint prevention programs to curb the triple threat. Millions of brains depend on it.

CARDIOVASCULAR REMODELING IN PATIENTS WITH HYPERTENSION WITH DIFFERENT DEGREES OF COGNITIVE IMPAIRMENT

Introduction: Recently, the concept of vascular cognitive impairment, combining all variants of cognitive decline due to cerebrovascular insufficiency, is actively being developed. This concept goes far beyond traditionally existing ideas about the problem of vascular cognitive disturbances. The aim of the study is to demonstrate the correlation between the indices of structural and functional rearrangement of the cardiovascular system and the state of intellectualmnemonic functions in patients with hypertension. Materials and methods: A comprehensive survey of 146 patients with hypertension of the II and III stage according to ESH / ESC 2013, 2017, 2018 has been performed. The study included patients with mild and moderate cognitive impairment (CI). Depending on the state of the cognitive sphere and on the basis of the results of the neuronpsychological testing, The patients were divided into 3 groups depending on the state of the cognitive sphere and on the basis of the results of the neuron-psychological testing with further comparisons of their clinical and instrumental data. Results: According to the results of our study, it has been found that an increase of the signs of cardiovascular remodeling was observed in patients with more pronounced changes in cognitive activity. The analysis of intracardiac hemodynamic parameters in patients of the studied groups revealed more significant pathological changes in patients with cognitive impairments than in patients without them. Patients with mild and moderate CI had significantly higher heart rates, left ventricular wall thickness (LV) which led to impairment of the diastolic function of LV and had already been registered in patients without cognitive dysfunction. Moreover, it increased with the appearance (mild) and growth of the degree (moderate) cognitive impairment. The average daily values of BP (SBP, DBP) in patients of all studied groups significantly exceeded the recommended norms, while in patients with moderate CI these rates were significantly higher than those in the group with mild CI (p = 0.028). In addition, the variability of systolic blood pressure was increasing simultaneously with the deterioration of cognitive function of our patients. Also, signs of remodeling were being observed during the study of the state of peripheral vessels (increase of peripheral resistance, pulsation index, linear velocity and thickening of the intima-media complex), which is the main cause of cognitive impairment and causes their appearance and reflects their degree. Conclusions: The presented study revealed a clear correlation between the degree of cognitive impairment and the degree of changes in the daily blood pressure profile, the most important of which were the average daily systolic blood pressure and systolic blood pressure variability. On the basis of the conducted research, in the future it will be possible to predict the level of the cognitive sphere involvement, depending on the state of the daily blood pressure profile, changes of the ventricle and vessels geometry, which will enable timely diagnosis of cognitive impairment and the prescription an adequate therapy.

Nimodipine activates neuroprotective signaling events and inactivates autophages in the VCID rat hippocampus

Background: Autophagy and phosphatidylinositol 3-kinase (PI3K)/Akt kinase pathways are implicated in cognitive decline associated with cerebrovascular lesions. This decline is reflected in the concept of vascular cognitive impairment and dementia (VCID). However, the underlying molecular mechanism and specific details regarding these types of cognitive deficits induced by chronic brain hypoperfusion have not been elucidated.Methods: We designed a method to evaluate these mechanisms. Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid artery (2VO) and randomly divided into three groups: Sham, Vehicle (2VO), and Nimodipine10 (2VO + nimodipine 10 mg/kg). Each group was studied for 4 weeks postoperatively and assessed by the Morris water maze.Results: The results of this study show that chronic brain hypoperfusion significantly increased the number of autophagic vacuoles with high LC3 II levels, but it decreased p-Akt and p-CREB levels, which were involved in the PI3K/Akt kinase pathway in the hippocampi of rats. Additionally, significant cognitive losses were observed following 2VO. Further analysis showed that, in VCID rats subjected to 2VO, nimodipine administration decreased autophagy, increased the Akt/CREB signaling pathway and significantly reduced brain damage.Conclusions: We concluded that neuronal pathology and activation of the autophagic and Akt/CREB signaling pathway caused by chronic brain hypoperfusion could suppress cognitive behavior, which may provide a novel way for the prevention of VCID. The results of this study indicate that nimodipine protected the brain from chronic brain hypoperfusion damage by suppressing autophagy and activating the Akt/CREB signaling pathway.

Vascular cognitive impairment, no dementia: diagnosis, prognosis, treatment, and prevention

The paper considers the concept of vascular cognitive impairment (CI), no dementia, their epidemiology, risk markers and pathological basis. It describes in detail the neuropsychological characteristics of CI, relevant diagnostic criteria, and clinical and neuroimaging diagnostic techniques. In addition to stroke, cerebral small vessel disease, which is characterized in the article in a modern light, is shown to play an important role in the development of moderate vascular CI. The course, prognosis of vascular cognitive impairment, and their determinants are discussed. Approaches to the treatment of the disease, including nicergoline therapy, and preventive measures with emphasis on physical activity are presented.

Recent updates on subcortical ischemic vascular dementia.

Vascular dementia (VaD) is a history-laden disease entity that dates back to the 19th century when arteriosclerotic brain atrophy due to hardening of the arteries was perceived as the major cause of senile dementia. Its existence had been overshadowed by the emergence of Alzheimer's disease (AD) in the past century and research on AD dominated the field of dementia. Interest in VaD has been revived in recent years as vascular lesions have been shown to make great contributions to the development of dementia, particularly in the elderly. VaD has now evolved into the concept of vascular cognitive impairment (VCI), which encompasses not only VaD but also AD with cerebrovascular disorder and VCI with no dementia. The concept of VCI is intended to maximize the therapeutic potential in dementia management because the vascular component may be amenable to therapeutic intervention particularly in the early stages of cognitive impairment. Subcortical ischemic vascular dementia (SIVD) is pathologically driven by severe stenosis and the occlusion of small vessels that culminate into white matter ischemia and multiple lacunar infarctions in the subcortical structures. The relatively slow progression of symptoms and clinical manifestations associated with cholinergic deficits often make the differentiation of SIVD from AD difficult. The recent development of in vivo amyloid imaging enabled further pathological breakdown of SIVD into pure SIVD and mixed dementia with subcortical ischemia based on the absence or existence of amyloid pathology in the brain. In this article, the authors reviewed the emerging concepts of VaD/VCI and the clinical manifestations, biomarkers, treatments, and preclinical models of SIVD based on the pathophysiologic mechanisms of the disease.

Vascular cognitive impairment

Clinically apparent and subclinical forms of vascular disease including stroke are important causes of cognitive dysfunction. In this review, we will describe the current nomenclature for vascular cognitive impairment (VCI) from the histopathological and clinical perspectives to raise awareness among practitioners about the interaction between conventional and novel vascular risk factors and VCI, with an emphasis on the prevention and risk factor modification. There is substantial evidence from observational studies and clinical trials that conventional risk factors such as hypertension, diabetes, dyslipidemia, smoking, and atrial fibrillation play a role in the development of VCI. Additional novel risk factors such as the metabolic syndrome have been associated with cognitive dysfunction as well. Targeting these risk factors will minimize the burden of VCI in our aging population. The concept of VCI has evolved to describe a continuum of cognitive disorders in which vascular brain injury plays a role, ranging from mild cognitive impairment to dementia. Future research is needed to clarify the role of risk factor modification in limiting vascular brain injury to prevent VCI and progression to dementia.

Vaskuläre Demenz

Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.

Neuropsychological Assessment

See related article, pages 2969–2972. Research on vascular factors in dementia and vascular cognitive impairment has gone through some major developments the past decades. Until 1993, the term multi-infarct dementia was used to distinguish dementia caused by one or more infarctions from Alzheimer disease.1 Research on cognitive functioning aimed at obvious cognitive impairment after a stroke, that was generally quantified with dementia screening methods. In 1993, the first set of diagnostic criteria of vascular dementia was introduced, which led to an expansion in the number of publications on the subject.2 In these criteria, several vascular mechanisms, pathology, and circumscript lesions or localizations were defined that may lead to vascular dementia. As the field evolved, new insights arose, accompanied with the acknowledgment that not all cognitive decline fulfilled the criteria of dementia. The concept of vascular cognitive impairment was formulated as an umbrella term that encompasses all cognitive deficits associated with vascular factors or mechanisms.3 Meanwhile, several attempts have been made to further differentiate specific patterns of cognitive impairment related to distinct vascular pathology. Efforts have been made with regard to poststroke dementia4,5 and subcortical vascular ischemic dementia.6 Still, the number of publications on cognitive deficits related to vascular factors is growing, and presently several studies aim to objectify even more subtle cognitive changes. In this issue of Stroke , …

Beyond mild cognitive impairment: vascular cognitive impairment, no dementia (VCIND)

Identifying the causes of dementia is important in the search for effective preventative and treatment strategies. The concept of mild cognitive impairment (MCI), as prodromal dementia, has been useful but remains controversial since in population-based studies it appears to be a limited predictor of progression to dementia. Recognising the relative contribution of neurodegenerative and vascular causes, as well as their interrelationship, may enhance predictive accuracy. The concept of vascular cognitive impairment (VCI) has been introduced to describe the spectrum of cognitive change related to vascular causes from early cognitive decline to dementia. A recent review of this concept highlighted the need for diagnostic criteria that encompass the full range of the VCI construct. However, very little is known regarding the mildest stage of VCI, generally termed 'vascular cognitive impairment, no dementia' (VCIND). Whether mild cognitive change in the context of neurodegenerative pathologies is distinct from that in the context of cerebrovascular diseases is not known. This is key to the definition of VCIND and whether it is possible to identify this state. Distinguishing between vascular (that is, VCIND) and non-vascular (that is, MCI) cognitive disorders and determining how well each might predict dementia may not be possible due to the overlap in pathologies observed in the older population. Here, we review the concept of VCIND in an effort to identify recent developments and areas of controversy in nosology and the application of VCIND for screening individuals at increased risk of dementia secondary to vascular disease and its risk factors.

Vascular disease and cognitive impairment

vascular risk factors; cerebrovascular disease; cognitive impairment; dementiaVascular disease seems to be important in cognitive impairment and dementia in the elderly.The entities implicated comprise various vascular risk factors and cerebrovascular diseaseincluding large cortical infarcts, single strategically-placed or multiple small infarcts, cerebralhemorrhage, cortical changes due to hypoperfusion (eg, hippocampal sclerosis, ischemic-anoxic damage, cortical laminar sclerosis), white matter changes, and a variety ofvasculopathies (eg, lipohyalinosis, cerebral autosomal dominant arteriopathy with subcorticalinfarcts and leukoencephalopathy (CADASIL), cerebral amyloid angiopathy). The traditionalview is that the two most common causes of dementia are vascular dementia and Alzheimer'sdisease. While there is general agreement that vascular dementia is caused by cerebrovasculardisease and its risk factors, their contribution to what we define clinically as Alzheimer'sdisease, theoretically characterized by the deposition of amyloid beta, is less clear. Morerecently, the concept of vascular cognitive impairment has been coined as an umbrella termthat encompasses all instances of cognitive impairment due to vascular risk factors andcerebrovascular disease, including vascular dementia, and Alzheimer’s disease with a vascularcontribution.1 As our understanding grows, new questions arise: does cerebrovascular disease,including white matter lesions and silent infarcts, lead to a specific pattern of cognitiveimpairment, and if so, how? Does cerebrovascular disease lead to a dementia syndromeindistinguishable from Alzheimer's disease? What are the molecular mechanisms underlyingthe associations between the various vascular risk factors and cognitive impairment? Dochanges in the microvasculature lead to the development of Alzheimer pathology?Leys et al. 2 summarized previous studies that explored the impact of clinical stroke on the riskof post-stroke dementia (PSD). Accordingly, stroke increases the risk of dementia, with aprevalence ranging from 13.6 to 32% within 3 months to 1 year after stroke, and after stroke

Modern concept of vascular cognitive impairment

Vascular cognitive impairment (VCI) has superseded vascular dementia and multi-infarct dementia as the concept to be used in cognitive decline due to cerebrovascular disease. The literature was reviewed with regard to the concept of VCI and its incidence, pathophysiological substrate, clinical features and management. A change in the diagnostic paradigm from the current Alzheimer-based definition of vascular dementia to VCI will allow the earlier identification of cases and will identify a different population from that recognized using the current criteria for vascular dementia. Case identification at the earliest possible stage affords the greatest opportunity for treatment that may slow the rate of progression.

Welcome Harmonizations

Welcome Harmonizations

The neuropsychology of vascular cognitive impairment: is there a specific cognitive deficit?

The concept of Vascular Cognitive Impairment (VCI) encompasses patients across the entire continuum of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from high-risk patients with no frank cognitive deficit (the “brain-at-risk” stage) through vascular dementia (VaD). There are accepted differences in the neuropsychological profile of patients with Alzheimer's disease (AD) and VaD. In patients with VaD, executive functions that tend to be disproportionately impaired include planning and sequencing, speed of mental processing, performance on unstructured tasks, and attention. Language production may be impaired in patients with VaD but primary language functions otherwise tend to be preserved. Patients with VaD also exhibit significantly more perseverations than patients with AD. Memory impairment is typically evident in patients with AD+CVD but memory impairment may also occur as a primary consequence of stroke in the posterior cerebral artery territory with involvement of the medial temporal lobe, or as a secondary consequence of a cognitive syndrome involving inattention due to primary executive dysfunction. Compared to VaD, patients with AD may exhibit greater deficits in functions (including memory) mediated by posterior cortical structures, such as the temporal and parietal lobes. AD patients exhibit a faster rate of information decay, reduced ability to benefit from cues to facilitate retrieval, and higher frequency of intrusion errors; in addition, certain aspects of language function, such as naming, may exacerbate deficits on verbal memory tasks. AD tends to affect lexicon while VaD tends to affect syntax. When patients with AD exhibit perseverations, they tend to be elicited by tests of semantic knowledge.

The concept of vascular cognitive impairment

Vascular dementia (VaD) is increasingly recognised to reflect an outmoded concept in that it identifies cases too late for preventive therapy to have an opportunity to prevent the development of dementia and uses a cognitive paradigm inappropriately based on Alzheimer's disease. A replacement is urgently required and a new concept, that of vascular cognitive impairment (VCI), has been proposed to meet this need. It is imperative that criteria for VCI are developed on the basis of knowledge and data rather than supposition and assumption, as was the case for VaD. This review details the state of knowledge that we have now reached concerning the fundamental points of severity and cognitive paradigm and also covers a number of other imaging-related essential points embracing atrophy, leukoaraiosis, infarct volume and infarct location. Finally, the increasingly important concept of mixed dementia (co-existent Alzheimer's disease and VCI) is discussed.

Vascular cognitive impairment and vascular dementia

The criteria for vascular dementia (VaD) depend on first diagnosing dementia using Alzheimer-type criteria, upon which are superimposed vascular events, usually following a stroke model. This if often inappropriate, however, as memory loss is not always prominent in VaD. Alzheimer-type criteria will not detect these patients, and much brain injury can occur without resulting in classical features of stroke. VaD is often only diagnosed when dementia is clinically manifest, already too late to influence the early progression of the disease. Moreover, the predominating consensus-based criteria have demonstrably poor reliability. These shortcomings in the diagnosis of VaD have led to the development of the concept of vascular cognitive impairment (VCI), a broader term that is intended to detect cognitive loss before the dementia advances beyond effective treatment. Criteria for VCI are in the early stages of development. A lack of data on the beginnings of cognitive loss has inhibited their formalization, but it appears that the level of cognition should be set at a sensitive rather than a specific level. Similarly, for routine purposes, neuroimaging evidence of any cerebrovascular disease may be sufficient to document VCI and specific localization is not required. The current clinical criteria for VaD are probably not applicable for the diagnosis of VCI since the presence of focal signs is inappropriate, and stepwise progression is more supportive than diagnostic of VCI. The purpose of defining the new concept of VCI is to identify preventable risk factors. Importantly, not only physical health but also mental health should be monitored and treated.

Cognitive impairment after stroke

The concept of vascular dementia is undergoing revision. The multi-infarct model and the Alzheimer's model of dementia, usually referred to as ‘multi-infarct dementia’, are gradually being replaced by a much broader concept of vascular cognitive impairment. This conceptual evolution reflects a more profound understanding of the pathogenic mechanisms that underlie this complex syndrome. As a consequence of this revision new diagnostic criteria have been established during the past 25 years, resulting in new problems with regard to precise disease definition and limited inter-rater reliability. The particular criteria chosen by a clinician or investigator to diagnose vascular dementia have a major impact on epidemiology, disease management and health economic estimates.

Cognitive impairment after stroke.

The concept of vascular dementia is undergoing revision. The multi-infarct model and the Alzheimer's model of dementia, usually referred to as 'multi-infarct dementia', are gradually being replaced by a much broader concept of vascular cognitive impairment. This conceptual evolution reflects a more profound understanding of the pathogenic mechanisms that underlie this complex syndrome. As a consequence of this revision new diagnostic criteria have been established during the past 25 years, resulting in new problems with regard to precise disease definition and limited inter-rater reliability. The particular criteria chosen by a clinician or investigator to diagnose vascular dementia have a major impact on epidemiology, disease management and health economic estimates.