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Biochimica Et Biophysica Acta May 2016In addition to its well-known role in energy metabolism in the body, insulin is a vasoactive hormone that regulates peripheral and cerebral blood flow and neuronal... (Review)
Review
In addition to its well-known role in energy metabolism in the body, insulin is a vasoactive hormone that regulates peripheral and cerebral blood flow and neuronal function. Vascular and metabolic dysfunctions are emerging risk factors for Alzheimer's disease (AD) and age-related dementias, and recent evidence suggests that the two pathways are constitutive and interrelated. As a result, an emphasis on correcting metabolic disorders is emerging as an important strategy in the treatment and prevention of age-related cognitive impairment and AD. We review the evidence regarding the unique and interactive effects of vascular and metabolic disorders in pathological brain aging, with special consideration of the role of insulin dysregulation in promoting AD pathologic processes and vascular brain injury. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
Topics: Age Factors; Alzheimer Disease; Animals; Brain; Dementia, Vascular; Glucose; Humans; Insulin; Insulin Resistance; Prediabetic State
PubMed: 26657615
DOI: 10.1016/j.bbadis.2015.11.013 -
CNS Neuroscience & Therapeutics Jan 2018Chronic cerebral circulation insufficiency (CCCI) may not be an independent disease; rather, it is a pervasive state of long-term cerebral blood flow insufficiency... (Review)
Review
Chronic cerebral circulation insufficiency (CCCI) may not be an independent disease; rather, it is a pervasive state of long-term cerebral blood flow insufficiency caused by a variety of etiologies, and considered to be associated with either occurrence or recurrence of ischemic stroke, vascular cognitive impairment, and development of vascular dementia, resulting in disability and mortality worldwide. This review summarizes the features and recent progress of CCCI, mainly focusing on epidemiology, experimental research, pathophysiology, etiology, clinical manifestations, imaging presentation, diagnosis, and potential therapeutic regimens. Some research directions are briefly discussed as well.
Topics: Animals; Brain Ischemia; Cerebrovascular Circulation; Dementia, Vascular; Humans; Ischemic Attack, Transient; Stroke
PubMed: 29143463
DOI: 10.1111/cns.12780 -
The Tohoku Journal of Experimental... Aug 1990Vascular dementia is almost always associated with organic brain lesions due to ischemia, not with arteriosclerosis alone. In Japan, more than 50% of dementia in... (Review)
Review
Vascular dementia is almost always associated with organic brain lesions due to ischemia, not with arteriosclerosis alone. In Japan, more than 50% of dementia in population older than 65 years are of vascular origin. Vascular dementia occurs with diffuse vascular lesions in the cerebral white matter or circumscribed lesions in particular areas such as the thalamus, anterior limb of the internal capsule, and cingulate gyrus, all of which constitute the ascending activating system or the limbic system. Vascular dementia is clinically characterized by stepwise progression, fluctuating course and predominant deterioration of intelligence with relative preservation of personality. Reversibility, disproportionate impairment of intelligence and personality, and dementia caused by a focal lesion observed in vascular dementia pose problems with regard to the classical concept of dementia. The similarity and difference between remitting dementia and disturbance of consciousness remain to be scrutinized.
Topics: Adult; Brain; Brain Damage, Chronic; Cohort Studies; Dementia; Dementia, Vascular; Diagnosis, Differential; Female; Humans; Intelligence; Intracranial Arteriosclerosis; Japan; Male; Middle Aged; Neurocognitive Disorders; Personality
PubMed: 2082504
DOI: 10.1620/tjem.161.supplement_39 -
Internal Medicine (Tokyo, Japan) Nov 2000
Topics: Antithrombins; Dementia, Vascular; Humans; Thrombin
PubMed: 11065234
DOI: 10.2169/internalmedicine.39.873 -
Seminars in Immunology Jan 2022Myocardial infarction is associated with increased risk for vascular dementia. In both myocardial infarction and vascular dementia, there is evidence that elevated... (Review)
Review
Myocardial infarction is associated with increased risk for vascular dementia. In both myocardial infarction and vascular dementia, there is evidence that elevated inflammatory biomarkers are associated with worsened clinical outcomes. Myocardial infarction leads to a systemic inflammatory response, which may contribute to recruitment or activation of myeloid cells, including monocytes, microglia, and perivascular macrophages, within the central nervous system. However, our understanding of the causative roles for these cells linking cardiac injury to the development and progression of dementia is incomplete. Herein, we provide an overview of inflammatory cellular and molecular links between myocardial infarction and vascular dementia and discuss strategies to resolve inflammation after myocardial infarction to limit neurovascular injury.
Topics: Humans; Dementia, Vascular; Myocardial Infarction; Monocytes; Macrophages; Inflammation
PubMed: 35227567
DOI: 10.1016/j.smim.2022.101600 -
International Journal of Stroke :... Jan 2023Cerebrovascular disease is a major cause of cognitive decline and dementia. This is referred to as vascular cognitive impairment (VCI). Diagnosing VCI is important,... (Review)
Review
Cerebrovascular disease is a major cause of cognitive decline and dementia. This is referred to as vascular cognitive impairment (VCI). Diagnosing VCI is important, among others to optimize treatment to prevent further vascular injury. This narrative review addresses challenges in current diagnostic approaches to VCI and potential future developments. First we summarize how diagnostic criteria for VCI evolved over time. We then highlight challenges in diagnosing VCI in clinical practice: assessment of severity of vascular brain injury on brain imaging is often imprecise and the relation between vascular lesion burden and cognitive functioning shows high intersubject variability. This can make it difficult to establish causality in individual patients. Moreover, because VCI is essentially an umbrella term, it lacks specificity on disease mechanisms, prognosis, and treatment. We see the need for a fundamentally different approach to diagnosing VCI, which should be more dimensional, including multimodal quantitative assessment of injury, with more accurate estimation of cognitive impact, and include biological definitions of disease that can support further development of targeted treatment. Recent developments in the field that can form the basis of such an approach are discussed.
Topics: Humans; Cognition Disorders; Dementia, Vascular; Stroke; Cognitive Dysfunction; Brain
PubMed: 35098817
DOI: 10.1177/17474930211073387 -
Stroke Nov 2022Binswanger disease is the small vessel form of vascular cognitive impairment and dementia. Deposition of Alzheimer disease proteins can begin in midlife and progress... (Review)
Review
Binswanger disease is the small vessel form of vascular cognitive impairment and dementia. Deposition of Alzheimer disease proteins can begin in midlife and progress slowly, whereas aging of the vasculature also can begin in midlife, continuing to progress into old age, making mixed dementia the most common type of dementia. Biomarkers facilitate the early diagnosis of dementias. It is possible to diagnose mixed dementia before autopsy with biomarkers for vascular disease derived from diffusor tensor images on magnetic resonance imaging and Alzheimer disease proteins, Aβ (amyloid β), and phosphorylated tau, in cerebrospinal fluid or in brain with positron emission tomography. The presence of vascular disease accelerates cognitive decline. Both misfolded proteins and vascular disease promote inflammation, which can be detected in cerebrospinal fluid by the presence of MMPs (matrix metalloproteinases), angiogenic growth factors, and cytokines. MMPs disrupt the blood-brain barrier and break down myelin, producing Binswanger disease's 2 main pathological features. Advances in detecting biomarkers in plasma will provide early detection of dementia and aided by machine learning and artificial intelligence, will enhance diagnosis and form the basis for early treatments.
Topics: Humans; Dementia, Vascular; Amyloid beta-Peptides; Alzheimer Disease; White Matter; Precision Medicine; Artificial Intelligence; Cognitive Dysfunction; Biomarkers; Positron-Emission Tomography; Cerebrovascular Disorders; Matrix Metalloproteinases; Cytokines
PubMed: 36148658
DOI: 10.1161/STROKEAHA.122.039211 -
Neural Plasticity 2020The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive... (Review)
Review
The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive impairment (VCI) is deemed to be the most common cognitive disorder in the elderly since it encompasses any degree of vascular-based cognitive decline. In different cognitive disorders, including VCI, transcranial magnetic stimulation (TMS) can be exploited as a noninvasive tool able to evaluate the cortical excitability, the propension to undergo neural plastic phenomena, and the underlying transmission pathways. Overall, TMS in VCI revealed enhanced cortical excitability and synaptic plasticity that seem to correlate with the disease process and progression. In some patients, such plasticity may be considered as an adaptive response to disease progression, thus allowing the preservation of motor programming and execution. Recent findings also point out the possibility to employ TMS to predict cognitive deterioration in the so-called "brains at risk" for dementia, which may be those patients who benefit more of disease-modifying drugs and rehabilitative or neuromodulatory approaches, such as those based on repetitive TMS (rTMS). Finally, TMS can be exploited to select the responders to specific drugs in the attempt to maximize the response and to restore maladaptive plasticity. While no single TMS index owns enough specificity, a panel of TMS-derived measures can support VCI diagnosis and identify early markers of progression into dementia. This work reviews all TMS and rTMS studies on VCI. The aim is to evaluate how cortical excitability, plasticity, and connectivity interact in the pathophysiology of the impairment and to provide a translational perspective towards novel treatments of these patients. Current pitfalls and limitations of both studies and techniques are also discussed, together with possible solutions and future research agenda.
Topics: Brain; Cortical Excitability; Dementia, Vascular; Humans; Neuronal Plasticity; Transcranial Magnetic Stimulation
PubMed: 33193753
DOI: 10.1155/2020/8820881 -
GeroScience Feb 2021Vascular cognitive impairment (VCI) is a term that encompasses a continuum of cognitive disorders with cerebrovascular pathology contribution, ranging from mild... (Review)
Review
Vascular cognitive impairment (VCI) is a term that encompasses a continuum of cognitive disorders with cerebrovascular pathology contribution, ranging from mild cognitive impairment to vascular dementia (VaD). VCI and VaD, thus, represent an interesting intersection between cardiovascular disease and neurodegenerative disorders such as Alzheimer's disease (AD) and a rising area of research in recent years. Although VCI and VaD research has identified various causes and explanations for disease development, many aspects remain unclear, particularly sex differences in VCI (e.g., epidemiology), unlike those available for cardiovascular disease and AD. Despite limited information in the literature, several studies have observed an association of estrogen receptor (ER) polymorphisms and VaD. If further explored, this association could provide valuable insights for novel therapeutic approaches. This review aims to provide a brief epidemiological overview and subsequent discussion exploring concepts of brain aging and involvement of estrogen receptors in potential mechanisms of VCI/VaD pathogenesis and treatment development.
Topics: Alzheimer Disease; Cognition Disorders; Cognitive Dysfunction; Dementia, Vascular; Female; Humans; Male; Receptors, Estrogen; Sex Factors
PubMed: 32902819
DOI: 10.1007/s11357-020-00263-4 -
BMJ (Clinical Research Ed.) May 2006
Topics: Alzheimer Disease; Dementia, Vascular; Humans; Intracranial Embolism
PubMed: 16690644
DOI: 10.1136/bmj.332.7550.1104