scholarly journals Cholesterol, Atherosclerosis, and APOE in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Potential Mechanisms and Therapy

2021 ◽  
Vol 13 ◽  
Author(s):  
Michael Tran Duong ◽  
Ilya M. Nasrallah ◽  
David A. Wolk ◽  
Catherine C. Y. Chang ◽  
Ta-Yuan Chang
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Cholesterol Metabolism ◽  
Experimental Models ◽  
Clinical Aspects ◽  
Chronic Neuroinflammation ◽  
Intracranial Atherosclerotic Disease ◽  
Atherosclerosis Risk Factors ◽  
A Minor

Vascular contributions to cognitive impairment and dementia (VCID) are a common cause of cognitive decline, yet limited therapies exist. This cerebrovascular disease results in neurodegeneration via acute, chronic, local, and systemic mechanisms. The etiology of VCID is complex, with a significant impact from atherosclerosis. Risk factors including hypercholesterolemia and hypertension promote intracranial atherosclerotic disease and carotid artery stenosis (CAS), which disrupt cerebral blood flow and trigger ischemic strokes and VCID. Apolipoprotein E (APOE) is a cholesterol and phospholipid carrier present in plasma and various tissues. APOE is implicated in dyslipidemia and Alzheimer disease (AD); however, its connection with VCID is less understood. Few experimental models for VCID exist, so much of the present information has been drawn from clinical studies. Here, we review the literature with a focus on the clinical aspects of atherosclerotic cerebrovascular disease and build a working model for the pathogenesis of VCID. We describe potential intermediate steps in this model, linking cholesterol, atherosclerosis, and APOE with VCID. APOE4 is a minor isoform of APOE that promotes lipid dyshomeostasis in astrocytes and microglia, leading to chronic neuroinflammation. APOE4 disturbs lipid homeostasis in macrophages and smooth muscle cells, thus exacerbating systemic inflammation and promoting atherosclerotic plaque formation. Additionally, APOE4 may contribute to stromal activation of endothelial cells and pericytes that disturb the blood-brain barrier (BBB). These and other risk factors together lead to chronic inflammation, atherosclerosis, VCID, and neurodegeneration. Finally, we discuss potential cholesterol metabolism based approaches for future VCID treatment.

The Spectrum of Cerebrovascular Disease and Associated Cognitive Decline

2019 ◽  
pp. 574-599
Author(s):  
Victoria J. Williams ◽  
Steven E. Arnold ◽  
David H. Salat
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Structure And Function ◽  
Vascular Risk Factors ◽  
Vascular Health ◽  
Vascular Risk ◽  
And Function

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.

Clinical Aspects of Non-Alzheimer Disease Dementias

2017 ◽  
Author(s):  
David Knopman
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cerebrovascular Disease ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Clinical Aspects ◽  
Key Words Dementia ◽  
Sleep Behavior

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN, and C9ORF72). Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

Abstract WP228: Clinical Characteristics of Hmong Patients Presenting with Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Haitham M Hussein ◽  
Bhavani Kashyap ◽  
Lauren O Erickson ◽  
Carol Droegemueller ◽  
Leah Hanson
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Univariate Analysis ◽  
Left Ventricular ◽  
Small Vessel ◽  
Arterial Calcification ◽  
Clinical Aspects ◽  
Intracranial Atherosclerotic Disease ◽  
The Usa ◽  
Hmong People

Introduction: Hmong people are originally from the mountainous areas of Southeastern China, Northern Vietnam, Laos, and Thailand. Large numbers have migrated to the USA. In response to a request from leaders of the Hmong community and given the lack of literature, this study was conducted to describe ischemic stroke in the Hmong patients at our comprehensive stroke center. Methods: Institutional GWTG database and charts for years 2010-2015 were retrospectively reviewed. Hmong patients were identified by their last names (18 clans) provided by the Hmong community leaders. Different demographic, social, and clinical aspects were reported and compared to white patients in a univariate analysis. Results: Forty-one Hmong and 1510 White were included in the analysis. Compared to Whites, Hmong patients were significantly younger (60±2.16 vs. 70±0.39 years # ), predominantly women (66% vs. 48%; p=0.03), less frequently covered by medical insurance (68% vs. 87% # ) and less frequently brought by ambulance (44% vs. 54% # ). Onset-to-door time, door-to-needle time, NIHSS at admission, and incidence of vascular risk factors was similar between the two groups; however, Hmong patients seemed to have poorly controlled risk factors with mean A1C 11±0.9% in diabetics (n=13) and mean LDL 116±6.4 mg/dL in hyperlipidemics (n=16). The most common stroke mechanisms were small vessel (31%) and intracranial atherosclerotic diseases (27%). Based on imaging in Hmong patients; 56% had intracranial arterial calcification, 53% had microaniopathic disease, 46% had intracranial stenosis, and 18% extracranial stenosis. On echocardiogram, 68% of Hmong had left ventricular hypertrophy, 54% had dilated left atrium, one patient had hypokinesis, and none had low ejection fraction. The length of stay and the rate of independent ambulation on discharge were not different between Hmong and Whites, however, a larger proportion of Hmong were discharged home (59% vs. 46%; p=0.05). # p≤0.0005 Conclusion: In this study population, Hmong patients suffered from poorly controlled risk factors, had high incidence of small vessel and intracranial atherosclerotic disease, low incidence of carotid disease and heart failure and utilized fewer resources than Whites.

scholarly journals Relationship between cortical microinfarcts and cognitive impairment in Alzheimer's disease

2012 ◽  
Vol 6 (3) ◽  
pp. 131-136 ◽  
Author(s):  
Benito P. Damasceno
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Vascular Diseases ◽  
Cerebral Hypoperfusion ◽  
Association Cortex ◽  
Vascular Risk ◽  
Behavioral Disturbances ◽  
Sedative Drugs

ABSTRACT Cerebrovascular disease and AD pathology co-exist in most dementia cases, and microinfarcts (MIs), particularly if cortical and multiple, play an additive and independent role in AD cognitive impairment. The main cause of cortical MIs is chronic cerebral hypoperfusion but occlusive vascular diseases, embolism and blood-brain barrier disruptions, isolated or combined, may also play a role. The precise mechanisms by which MIs cause cognitive impairment are not well known, but one plausible explanation is that they are widespread and accompanied by diffuse hypoperfusion, hypoxia, oxidative stress and inflammation, particularly in the watershed areas of the tertiary association cortex, and hence could damage cognition networks and explain many of AD's cognitive and behavioral disturbances. Therefore, it is crucial to control vascular risk factors and avoid uncontrolled use of the antihypertensives, neuroleptics and other sedative drugs frequently prescribed to AD patients.

scholarly journals In Vivo Studies of Protein Misfolding and Neurodegeneration Induced by Metabolic Syndrome Relative to Chronic Cerebral Hypoperfusion: A Critical Review

2020 ◽  
Author(s):  
María I. Herrera ◽  
Juan P. Luaces ◽  
Lucas D. Udovin ◽  
Nicolás Toro-Urrego ◽  
Matilde Otero-Losada ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Protein Misfolding ◽  
Basic Research ◽  
Experimental Models ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
In Vivo Studies

Metabolic syndrome (MetS) leads to microvascular dysfunction and chronic cerebral hypoperfusion (CCH) in an insidious way. Clinical evidence and several rodent models have contributed to determining the neurodegenerative effect of a sustained decrease in cerebral blood flow (CBF). Protein misfolding and aggregation derived from CCH might account for the establishment of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). However, the complex and multifactorial etiology of cerebrovascular disease demands the combination of experimental models in scientific research. In this sense, the present work aims at summarizing the differential available rodent paradigms for studying the establishment of cognitive decline resulting from protein misfolding induced by MetS in association with CCH. Revising experimental findings in the field will help further basic research on the pathophysiology of cerebrovascular disease and the future testing of protein-remodeling factors as neuroprotective agents for the prevention of cognitive impairment.

Clinical Aspects of Non-Alzheimer Disease Dementias

2017 ◽  
Author(s):  
David Knopman
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cerebrovascular Disease ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Clinical Aspects ◽  
Key Words Dementia ◽  
Sleep Behavior

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN, and C9ORF72). Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

Vascular Risk Factors, Vascular Diseases, and Imaging Findings in a Hospital-based Cohort of Mild Cognitive Impairment Types

2018 ◽  
Vol 15 (7) ◽  
pp. 679-690 ◽  
Author(s):  
Cecilia Camarda ◽  
Carmela Pipia ◽  
Delia Azzarello ◽  
Iacopo Battaglini ◽  
Giovanni Romeo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Brain Atrophy ◽  
Vascular Diseases ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Amnestic Mci ◽  
Multiple Domain

Background: Mild Cognitive Impairment (MCI) is a transitional state between normal cognition and dementia. Objective: The aim of this study is to investigate the role of vascular risk factors, vascular diseases, cerebrovascular disease and brain atrophy in a large hospital-based cohort of MCI types including 471 amnestic MCI (a-MCI), 693 amnestic MCI multiple domain (a-MCImd), 322 single non-memory MCI (snm-MCI), and 202 non amnestic MCI multiple domain (na-MCImd). For comparison, 1,005 neurologically and cognitively healthy subjects were also evaluated. Method: Several vascular risk factors and vascular diseases were assessed. All participants underwent neurological, neuropsychological and behavioural assessments as well as carotid ultrasonography and standard brain MRI. Multinomial logistic regression models on the MCI cohort with the NCH group and a-MCI type as reference categories were used to assess the effects of the variables evaluated on the estimated probability of one of the four MCI types. Results: This study demonstrates that cerebrovascular disease contributes substantially to the risk of non-memory MCI types and a-MCImd type, and that brain atrophy is present in all MCI types and is greater in multiple domain types particularly in the na-MCI type. Conclusion: Improving detection and control of cerebrovascular disease in aging individuals should be mandatory. Since the incidence of MCI and dementia will be expected to rise because of the progressive life expectancy, a better management of cerebrovascular disease could indeed prevent or delay the onset of MCI, or could delay progression of MCI to dementia.

Clinical Aspects of Non-Alzheimer Disease Dementias

2017 ◽  
Author(s):  
David Knopman
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cerebrovascular Disease ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Clinical Aspects ◽  
Key Words Dementia ◽  
Sleep Behavior

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN, and C9ORF72). Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

Clinical Aspects of Non-Alzheimer Disease Dementias

2017 ◽  
Author(s):  
David Knopman
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cerebrovascular Disease ◽  
Lewy Body ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Lewy Body Disease ◽  
Clinical Aspects ◽  
Key Words Dementia ◽  
Sleep Behavior

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN, and C9ORF72). Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment

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