Vascular Cognitive Impairment and Dementia

Journal of the American College of Cardiology, Journal Year: 2019, Volume and Issue: 73(25), P. 3326 - 3344

Published: June 24, 2019

Language: Английский

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NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Sept. 16, 2021

Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD

Language: Английский

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White matter degeneration in vascular and other ageing‐related dementias

Journal of Neurochemistry, Journal Year: 2017, Volume and Issue: 144(5), P. 617 - 633

Published: Dec. 6, 2017

Abstract Advances in neuroimaging have enabled greater understanding of the progression cerebral degenerative processes associated with ageing‐related dementias. Leukoaraiosis or rarefied white matter ( WM ) originally described on computed tomography is one most prominent changes which occurs older age. White hyperintensities WMH evident magnetic resonance imaging become commonplace to describe relation cognitive dysfunction, types stroke injury, small vessel disease and neurodegenerative disorders including Alzheimer's disease. Substrates degeneration collectively include myelin loss, axonal abnormalities, arteriolosclerosis parenchymal resulting from lacunar infarcts, microinfarcts, microbleeds perivascular spacing. cells incorporating astrocytes, oligodendrocytes, pericytes microglia are recognized as key cellular components gliovascular unit. They respond ongoing pathological different ways leading disruption The robust alterations involve oligodendrocyte loss astrocytic clasmatodendrosis displacement water channel protein, aquaporin 4. These modifications likely precede capillary tissue oedema, breach blood–brain barrier induction a chronic hypoxic state deep . Several pathophysiological mechanisms proposed explain how commencing haemodynamic within vascular system impact dysfunction. Animal models simulating hypoperfusion man paved way for several translational opportunities. Various compounds variable efficacies been tested reduce oxidative stress, inflammation damage Our review demonstrates that encompasses multiple substrates therefore more than pharmacological approach necessary preserve function prevent impairment. image This article part Special Issue “Vascular Dementia”

Language: Английский

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Vascular Cognitive Impairment (VCI)

Neurotherapeutics, Journal Year: 2021, Volume and Issue: 19(1), P. 68 - 88

Published: Dec. 22, 2021

Vascular cognitive impairment (VCI) is predominately caused by vascular risk factors and cerebrovascular disease. VCI includes a broad spectrum of disorders, from mild to dementia ischemic or hemorrhagic stroke, alone in combination with neurodegeneration including Alzheimer's disease (AD) AD-related dementia. accounts for at least 20-40% all diagnosis. Growing evidence indicates that pathology the most important contributor dementia, additive synergistic interactions neurodegenerative pathology. The common underlying mechanism chronic age-related dysregulation CBF, although other such as inflammation cardiovascular dysfunction play role. are prevalent if measured midlife they predict later life. Particularly, hypertension, high cholesterol, diabetes, smoking each associated 20 40% increased Control these multimodality strategies an inclusion lifestyle modification promising strategy treatment prevention VCI. In this review, we present recent developments VCI, its mechanisms, diagnostic criteria, neuroimaging correlates, determinants, current intervention We have also summarized relevant literature field

Language: Английский

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Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment

Theranostics, Journal Year: 2022, Volume and Issue: 12(4), P. 1639 - 1658

Published: Jan. 1, 2022

The prevalence of cerebrovascular disease increases with age, placing the elderly at a greater lifetime risk for dementia. Vascular cognitive impairment (VCI) encompasses spectrum deficits from mild to VCI and its most severe form, vascular dementia (VaD), is becoming major public health concern worldwide. As growing efforts are being taken understand VaD in animal models humans, pathogenesis actively explored. It postulated that chronic cerebral hypoperfusion (CCH) cause VCI. CCH activates molecular cellular injury cascade leads breakdown blood brain barrier (BBB) neurodegeneration. BBB tightly regulates movement substances between brain, thereby regulating microenvironment within parenchyma. Here we illustrate how damage causal through increased activation pathways related excitotoxicity, oxidative stress, inflammation matrix metalloproteinases lead downstream perivascular damage, leukocyte infiltration white matter changes brain. Thus, CCH-induced may initiate contribute vicious cycle, resulting progressive neuropathological This review outlines mechanisms govern during highlights clinical evidence identifying at-risk patients.

Language: Английский

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Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 11, 2023

Abstract Vascular cognitive impairment and dementia (VCID) is commonly caused by vascular injuries in cerebral large small vessels a key driver of age-related decline. Severe VCID includes post-stroke dementia, subcortical ischemic multi-infarct mixed dementia. While acknowledged as the second most common form after Alzheimer’s disease (AD) accounting for 20% cases, AD frequently coexist. In VCID, vessel (cSVD) often affects arterioles, capillaries, venules, where arteriolosclerosis amyloid angiopathy (CAA) are major pathologies. White matter hyperintensities, recent infarcts, lacunes presumed origin, enlarged perivascular space, microbleeds, brain atrophy neuroimaging hallmarks cSVD. The current primary approach to cSVD treatment control risk factors such hypertension, dyslipidemia, diabetes, smoking. However, causal therapeutic strategies have not been established partly due heterogeneous pathogenesis this review, we summarize pathophysiology discuss probable etiological pathways focusing on hypoperfusion/hypoxia, blood–brain barriers (BBB) dysregulation, fluid drainage disturbances, inflammation define potential diagnostic targets

Language: Английский

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The role of inflammasomes in vascular cognitive impairment

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Jan. 9, 2022

There is an increasing prevalence of Vascular Cognitive Impairment (VCI) worldwide, and several studies have suggested that Chronic Cerebral Hypoperfusion (CCH) plays a critical role in disease onset progression. However, there limited understanding the underlying pathophysiology VCI, especially relation to CCH. Neuroinflammation significant contributor progression VCI as increased systemic levels proinflammatory cytokine interleukin-1β (IL-1β) has been extensively reported patients. Recently it established CCH can activate inflammasome signaling pathways, involving NLRP3 AIM2 inflammasomes critically regulate IL-1β production. Given neuroinflammation early event important we understand its molecular cellular mechanisms enable development disease-modifying treatments reduce structural brain damage cognitive deficits are observed clinically elderly. Hence, this review aims provide comprehensive insight into involved pathogenesis CCH-induced VCI.

Language: Английский

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Chronic cerebral hypoperfusion: a critical feature in unravelling the etiology of vascular cognitive impairment

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: June 12, 2023

Vascular cognitive impairment (VCI) describes a wide spectrum of deficits related to cerebrovascular diseases. Although the loss blood flow cortical regions critically involved in processes must feature as main driver VCI, underlying mechanisms and interactions with disease remain be fully elucidated. Recent clinical studies cerebral measurements have supported role chronic hypoperfusion (CCH) major vascular pathology manifestations VCI. Here we review pathophysiological well neuropathological changes CCH. Potential interventional strategies for VCI are also reviewed. A deeper understanding how CCH can lead accumulation VCI-associated could potentially pave way early detection development disease-modifying therapies, thus allowing preventive interventions instead symptomatic treatments.

Language: Английский

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Animal Models of Chronic Cerebral Hypoperfusion: From Mouse to Primate

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(24), P. 6176 - 6176

Published: Dec. 7, 2019

Vascular cognitive impairment (VCI) or vascular dementia occurs as a result of brain ischemia and represents the second most common type after Alzheimer's disease. To explore underlying mechanisms VCI, several animal models chronic cerebral hypoperfusion have been developed in rats, mice, primates. We established mouse model by narrowing bilateral carotid arteries with microcoils, eventually resulting hippocampal atrophy. In addition, white matter infarct-related damage motor dysfunction has also asymmetric artery surgery. Although experiments studying performed rodents because ease handling greater ethical acceptability, non-human primates appear to represent best for study due their similarities much larger volume amyloid β depositions like humans. Therefore, we recently baboon VCI through three-vessel occlusion (both internal left vertebral artery). this review, hypoperfusion, from primate, are extensively discussed aid better understanding pathophysiology VCI.

Language: Английский

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Association Between Blood Pressure Variability and Cerebral Small‐Vessel Disease: A Systematic Review and Meta‐Analysis

Journal of the American Heart Association, Journal Year: 2019, Volume and Issue: 9(1)

Published: Dec. 24, 2019

Background Research links blood pressure variability ( BPV ) with stroke; however, the association cerebral small‐vessel disease CSVD remains unclear. As and mean are interrelated, it uncertain whether adds additional information to understanding cerebrovascular morphological characteristics. Methods Results A systematic review was performed from inception until March 3, 2019. Eligibility criteria included population, adults without stroke (<4 weeks); exposure, quantified by any metric over duration; comparison, (1) low versus high or (2) people ; outcomes, as subcortical infarct, lacunae, white matter hyperintensities, microbleeds, enlarged perivascular spaces; standardized difference in . total of 27 articles were meta‐analyzed, comprising 12 309 unique brain scans. 31 odds ratios OR s) pooled, indicating that higher systolic associated for OR, 1.27; 95% CI, 1.14–1.42; I 2 =85%) independent pressure. Likewise, diastolic 1.30; 1.14–1.48; =53%) There no evidence a pairwise interaction between systolic/diastolic /mean s P =0.47), nor =0.58). Fifty‐four differences pooled provided similar results =0.38) =0.70). Conclusions On basis available studies, However, more high‐quality longitudinal data required elucidate contributes variance

Language: Английский

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