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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 -
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 -
European Review For Medical and... Sep 2020Vascular dementia is the second-most cause of dementia, characterized by cerebral infarcts, white matter lesions, myelin loss and often amyloid angiopathy. Hence,... (Review)
Review
Vascular dementia is the second-most cause of dementia, characterized by cerebral infarcts, white matter lesions, myelin loss and often amyloid angiopathy. Hence, vascular damage is a critical cause of neuronal loss and synaptic disintegration. Abnormal neuroinflammation, autophagy and apoptosis are the prerequisite factors for endothelial and neuronal cell damage. This leads to the onset and progression of cerebrovascular disorders and cognitive dysfunction. The innate immune cells, pattern recognition receptors, Toll-like receptor-4 and related inflammatory mechanisms disrupt cerebrovascular integrity via glial activation and increased pro-inflammatory interleukins and TNFα. Inflammasome polymorphisms and multi-faceted neuro-immune interactions further integrate systemic and central inflammatory pathways, which induce vascular tissue injury and neurodegeneration. Specifically, chronic cerebral hypoperfusion disrupts the self-cannibalization mechanism of autophagy via altered expression of autophagy-specific proteins, Beclin-1, LC3 and P62. The deregulated autophagy pathway causes neuronal loss, hippocampal shrinkage, and ultimate loss in synaptic plasticity. The vascular dementia models typically exhibit downregulated anti-apoptotic Bcl-2 and upregulated pro-apoptotic Bax, cleaved caspase-3, and cleaved-PARP levels in the brain, for which modulated p38 MAPK and JNK phosphorylation pathways play a vital role. Endoplasmic stress-induced apoptosis, calcium overload and glutamate excitotoxicity in combination with ASK1-MAPK signaling mechanism also contribute to the cerebrovascular pathology. Vascular injury reduces neurological scores and increases the infarct volume, DNA damage and neuronal apoptosis in ischemia/reperfusion injury. Additionally, synergistic and additive interactions between inflammasome, autophagy and apoptotic signaling pathways augment symptoms of vascular neurodegeneration. Overall, the current review enlightens the key risk factors and underlying mechanism triggering vascular dementia. The review additionally informs the challenges associated while treating vascular dysfunction, and highlights the need for targeted drugs for reducing cerebrovascular damage.
Topics: Animals; Apoptosis; Dementia, Vascular; Humans; Inflammation
PubMed: 33015803
DOI: 10.26355/eurrev_202009_23048 -
Dementia and Geriatric Cognitive... 2017Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VaD), has only achieved recognition in the last 4 decades. Since its original description, the... (Review)
Review
BACKGROUND
Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VaD), has only achieved recognition in the last 4 decades. Since its original description, the characterization, etiological understanding, and therapeutic direction of MID and other VaD subtypes has progressed at an astounding rate.
SUMMARY
This paper divides the landmark discoveries and emergence of new research strategies for MID into decade-defining patterns so that a condensed picture of the total history of MID and its eventual inclusion as a VaD subtype emerges. This paper follows the first descriptive decade, a shift to a preventative focus, a renewed interest coinciding with timely advances in research technology, and a hopeful return to treatment possibilities for VaD.
KEY MESSAGE
Concisely tracing the historical lineage of the modern understanding of MID, both as a singular entity and as part of the VaD con-stellation of disorders, provides a novel perspective on the foundation upon which future advances in combating vascular contributions to dementia will be based.
PubMed: 28626470
DOI: 10.1159/000470836 -
Frontiers in Aging Neuroscience 2021Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD); where Alzheimer's accounts for 60-70% of cases of dementia and VaD... (Review)
Review
Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD); where Alzheimer's accounts for 60-70% of cases of dementia and VaD accounts for 20% of all dementia cases. VaD is defined as a reduced or lack of blood flow to the brain that causes dementia. VaD is also known occasionally as vascular contributions to cognitive impairment and dementia (VCID) or multi-infarct dementia (MID). VCID is the condition arising from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior, and VaD is the most severe stage while MID is produced by the synergistic effects caused by multiple mini strokes in the brain irrespective of specific location or volume. There are also subtle differences in the presentation of VaD in males and females, but they are often overlooked. Since 1672 when the first case of VaD was reported until now, sex and gender differences have had little to no research done when it comes to the umbrella term of dementia in general. This review summarizes the fundamentals of VaD followed by a focus on the differences between sex and gender when an individual is diagnosed. In addition, we provide critical evidence concerning sex and gender differences with a few of the main risk factors of VaD including pre-existing health conditions and family history, gene variants, aging, hormone fluctuations, and environmental risk factors. Additionally, the pharmaceutical treatments and possible mitigation of risk factors is explored.
PubMed: 34566624
DOI: 10.3389/fnagi.2021.720715 -
Ochsner Journal 2003Many cases of age-related cognitive dementia are caused by cerebrovascular lesions, and various vascular syndromes can lead to cognitive impairment and dementia....
Many cases of age-related cognitive dementia are caused by cerebrovascular lesions, and various vascular syndromes can lead to cognitive impairment and dementia. Repeated cortical infarcts due to embolic disease of the heart or major cerebral vessels can cause progressive deterioration towards dementia and incapacitation. In classic multi-infarct dementia, cognitive deterioration is stepwise rather than smoothly progressive. While diagnostic technologies have vastly improved and added to general knowledge of the pathology of cerebrovascular disease, MRI, PET, and transcranial Doppler scans have demonstrated that significant white matter change is possible without clinically recognized TIA or completed stroke. In addition, patients may have initial complaints that are not serious enough to produce changes on mental status examination. Many patients have mixed dementia, exhibiting aspects of both degenerative brain disease and clinical evidence of strokes or significant changes on MRI scan. The overlap between vascular and degenerative disease is significant, yet the exact interaction of the pathophysiology of the vascular lesions and the degenerative changes is not known. The treatment of vascular or mixed dementia involves control of the risk factors for continued vascular events and treatment with the cholinesterase inhibitors.
PubMed: 22470255
DOI: No ID Found -
Oxidative Medicine and Cellular... 2021Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VD), is responsible for at least 15 to 20 percent of dementia in the elderly. Mitochondrial...
Mitochondrial Protection and Against Glutamate Neurotoxicity via Shh/Ptch1 Signaling Pathway to Ameliorate Cognitive Dysfunction by Kaixin San in Multi-Infarct Dementia Rats.
Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VD), is responsible for at least 15 to 20 percent of dementia in the elderly. Mitochondrial dysfunctions and glutamate neurotoxicity due to chronic hypoperfusion and oxidative stress were regarded as the major risk factors in the pathogenesis. (KXS), a classic prescription of , was applied to treatment for "amnesia" and has been demonstrated to alleviate the cognitive deficit in a variety of dementias, including MID. However, little is known whether mitochondria and glutamate are associated with the protection of KXS in MID treatment. The aim of this study was to investigate the role of KXS in improving the cognitive function of MID rats through strengthening mitochondrial functions and antagonizing glutamate neurotoxicity via the Shh/Ptch1 signaling pathway. Our data showed that KXS significantly ameliorated memory impairment and hippocampal neuron damage in MID rats. Moreover, KXS improved hippocampal mitochondrial functions by reducing the degree of mitochondrial swelling, increasing the mitochondrial membrane potential (MMP), and elevating the energy charge (EC) and ATP content in MID rats. As expected, the concentration of glutamate and the expression of p-NMDAR1 were significantly reduced by KXS in the brain tissue of MID rats. Furthermore, our results showed that KXS noticeably activated the Shh/Ptch1 signaling pathway which was demonstrated by remarkable elevations of Ptch1, Smo, and Gli1 protein levels in the brain tissue of MID rats. Intriguingly, the inhibition of the Shh signaling pathway with cyclopamine significantly inhibited the protective effects of KXS on glutamate-induced neurotoxicity in PC12 cells. To sum up, these findings suggested that KXS protected MID rats from memory loss by rescuing mitochondrial functions as well as against glutamate neurotoxicity through activating Shh/Ptch1 signaling pathway.
Topics: Animals; Cognitive Dysfunction; Dementia, Multi-Infarct; Disease Models, Animal; Drugs, Chinese Herbal; Glutamic Acid; Male; Memory Disorders; Mitochondria; Neurons; Patched-1 Receptor; Rats, Sprague-Dawley; Signal Transduction; Rats
PubMed: 34306310
DOI: 10.1155/2021/5590745 -
Experimental and Therapeutic Medicine Nov 2020Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's...
Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems.
PubMed: 32963600
DOI: 10.3892/etm.2020.9198 -
Journal of Cerebral Blood Flow and... Nov 2023Vascular cognitive impairment (VCI) refers to all forms of cognitive disorder related to cerebrovascular diseases, including vascular mild cognitive impairment,... (Review)
Review
Vascular cognitive impairment (VCI) refers to all forms of cognitive disorder related to cerebrovascular diseases, including vascular mild cognitive impairment, post-stroke dementia, multi-infarct dementia, subcortical ischemic vascular dementia (SIVD), and mixed dementia. Among the causes of VCI, more attention has been paid to SIVD because the causative cerebral small vessel pathologies are frequently observed in elderly people and because the gradual progression of cognitive decline often mimics Alzheimer's disease. In most cases, small vessel diseases are accompanied by cerebral hypoperfusion. In mice, prolonged cerebral hypoperfusion is induced by bilateral carotid artery stenosis (BCAS) with surgically implanted metal micro-coils. This cerebral hypoperfusion BCAS model was proposed as a SIVD mouse model in 2004, and the spreading use of this mouse SIVD model has provided novel data regarding cognitive dysfunction and histological/genetic changes by cerebral hypoperfusion. Oxidative stress, microvascular injury, excitotoxicity, blood-brain barrier dysfunction, and secondary inflammation may be the main mechanisms of brain damage due to prolonged cerebral hypoperfusion, and some potential therapeutic targets for SIVD have been proposed by using transgenic mice or clinically used drugs in BCAS studies. This review article overviews findings from the studies that used this hypoperfused-SIVD mouse model, which were published between 2004 and 2021.
Topics: Humans; Mice; Animals; Aged; Carotid Stenosis; Dementia, Vascular; Cognitive Dysfunction; Cerebrovascular Disorders; Disease Models, Animal; Brain Ischemia; Mice, Inbred C57BL
PubMed: 36883344
DOI: 10.1177/0271678X231154597 -
Neurologia (Barcelona, Spain) May 2015A review of current criteria for the diagnosis of categories related with vascular cognitive impairment, in particular the nomenclature, diagnostic criteria, and... (Review)
Review
OBJECTIVE
A review of current criteria for the diagnosis of categories related with vascular cognitive impairment, in particular the nomenclature, diagnostic criteria, and differential clinical-radiological findings.
DEVELOPMENT
The criteria for the diagnosis of vascular cognitive impairment have evolved, but available criteria were designed basically for differentiating between vascular dementia and dementia due to Alzheimer disease, and for research purposes. Nevertheless, in clinical practice precise elements are required for: 1) Clinical diagnosis of dementia and mild cognitive impairment; 2) Clinical and neuroimaging criteria for identification of the various cerebrovascular lesions associated with cognitive dysfunction, and 3) A formulation of the aetiogenic-pathogenic relationship between cognitive impairment and cerebrovascular lesions. For this reason, a review was carried out on the diagnostic elements of vascular cognitive impairment categories, classification, and their most relevant characteristics. It highlights the characteristic for the diagnosis of multi-infarction dementia, strategic single infarct dementia, small vessel disease with dementia, mixed dementia, and vascular mild cognitive impairment.
CONCLUSIONS
Standardisation is required, by a multidisciplinary expert team, as regards nomenclature and criteria for the diagnosis of the full spectrum associated with vascular cognitive impairment and especially for vascular dementia and its categories.
Topics: Alzheimer Disease; Brain; Cognitive Dysfunction; Dementia, Vascular; Diagnosis, Differential; Humans; Neuroimaging; Stroke
PubMed: 22739039
DOI: 10.1016/j.nrl.2011.12.014