Materiały źródłowe

• #1 Vascular Dementia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430817/

  Vascular dementia is distinguished from other forms of MND in that it results from brain ischemia or hemorrhage and not from one or more underlying neurodegenerative proteinopathies. […] The pathogenesis of vascular dementia is understood as follows: vascular risk factors lead to cerebrovascular disease that, in turn, causes brain injury; the resulting disruption of cognitive networks culminates in vascular dementia. […] Neuropathologic studies illustrate vascular dementia’s high degree of heterogeneity, with multiple and overlapping types of cerebrovascular disease damaging multiple sites in the vascular tree. […] Cardiovascular risk factors for vascular dementia include smoking, hyperlipidemia, hypertension, diabetes, atrial fibrillation, obesity, and physical inactivity, among others.

• #2 Etiology, clinical manifestations, and diagnosis of vascular dementia – UpToDate

  https://www.uptodate.com/contents/etiology-clinical-manifestations-and-diagnosis-of-vascular-dementia

  Vascular cognitive impairment and dementia (VCID) refers to those syndromes that are felt to be caused in whole or in part by cerebrovascular disease or impaired cerebral blood flow. […] Vascular dementia refers to any dementia that is primarily caused by cerebrovascular disease or impaired cerebral blood flow, or in which cerebrovascular disease or impaired cerebral blood flow is a contributing causative factor.

• #3 Vascular Dementia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430817/

  Vascular dementia is distinguished from other forms of MND in that it results from brain ischemia or hemorrhage and not from one or more underlying neurodegenerative proteinopathies. […] The pathogenesis of vascular dementia is understood as follows: vascular risk factors lead to cerebrovascular disease that, in turn, causes brain injury; the resulting disruption of cognitive networks culminates in vascular dementia. […] Neuropathologic studies illustrate vascular dementia’s high degree of heterogeneity, with multiple and overlapping types of cerebrovascular disease damaging multiple sites in the vascular tree. […] Cardiovascular risk factors for vascular dementia include smoking, hyperlipidemia, hypertension, diabetes, atrial fibrillation, obesity, and physical inactivity, among others.

• #4 Vascular Dementia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430817/

  Vascular dementia is distinguished from other forms of MND in that it results from brain ischemia or hemorrhage and not from one or more underlying neurodegenerative proteinopathies. […] The pathogenesis of vascular dementia is understood as follows: vascular risk factors lead to cerebrovascular disease that, in turn, causes brain injury; the resulting disruption of cognitive networks culminates in vascular dementia. […] Neuropathologic studies illustrate vascular dementia’s high degree of heterogeneity, with multiple and overlapping types of cerebrovascular disease damaging multiple sites in the vascular tree. […] Cardiovascular risk factors for vascular dementia include smoking, hyperlipidemia, hypertension, diabetes, atrial fibrillation, obesity, and physical inactivity, among others.

• #5 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. […] The term of VaD substantially means „disease with a cognitive impairment resulting from cerebrovascular disease and ischemic or hemorrhagic brain injury”. […] The cognitive impairment attributable to cerebrovascular disease is a rapidly escalating public health problem. […] Vascular cognitive impairment is not a regular pathogenetic entity. Multiple small thromboembolic strokes or strokes in strategic locations such as the thalamus, frontal lobe or temporal lobes may cause cognitive impairment and frequently occur without classical stroke-like symptoms. […] In VaD, the majority of patients instead present widespread microangiopathy-related cerebral damage, which is often clinically silent or is accompanied by unspecific neurological signs.

• #6 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. […] Many subtypes of vascular dementia have been described. The spectrum includes (1) mild vascular cognitive impairment, (2) multi-infarct dementia, (3) vascular dementia due to a strategic single infarct, (4) vascular dementia due to lacunar lesions, (5) vascular dementia due to hemorrhagic lesions, (6) Binswanger disease, (7) subcortical vascular dementia, and (8) mixed dementia (combination of AD and vascular dementia). […] Vascular disease produces either focal or diffuse effects on the brain and causes cognitive decline. Focal cerebrovascular disease occurs secondary to thrombotic or embolic vascular occlusions. Common areas of the brain associated with cognitive decline are the white matter of the cerebral hemispheres and the deep gray nuclei, especially the striatum and the thalamus. Hypertension is the major cause of diffuse disease, and in many patients, both focal and diffuse disease are observed together. The 3 most common mechanisms of vascular dementia are multiple cortical infarcts, a strategic single infarct, and small vessel disease.

• #7 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. […] Many subtypes of vascular dementia have been described. The spectrum includes (1) mild vascular cognitive impairment, (2) multi-infarct dementia, (3) vascular dementia due to a strategic single infarct, (4) vascular dementia due to lacunar lesions, (5) vascular dementia due to hemorrhagic lesions, (6) Binswanger disease, (7) subcortical vascular dementia, and (8) mixed dementia (combination of AD and vascular dementia). […] Vascular disease produces either focal or diffuse effects on the brain and causes cognitive decline. Focal cerebrovascular disease occurs secondary to thrombotic or embolic vascular occlusions. Common areas of the brain associated with cognitive decline are the white matter of the cerebral hemispheres and the deep gray nuclei, especially the striatum and the thalamus. Hypertension is the major cause of diffuse disease, and in many patients, both focal and diffuse disease are observed together. The 3 most common mechanisms of vascular dementia are multiple cortical infarcts, a strategic single infarct, and small vessel disease.

• #8 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. […] Many subtypes of vascular dementia have been described. The spectrum includes (1) mild vascular cognitive impairment, (2) multi-infarct dementia, (3) vascular dementia due to a strategic single infarct, (4) vascular dementia due to lacunar lesions, (5) vascular dementia due to hemorrhagic lesions, (6) Binswanger disease, (7) subcortical vascular dementia, and (8) mixed dementia (combination of AD and vascular dementia). […] Vascular disease produces either focal or diffuse effects on the brain and causes cognitive decline. Focal cerebrovascular disease occurs secondary to thrombotic or embolic vascular occlusions. Common areas of the brain associated with cognitive decline are the white matter of the cerebral hemispheres and the deep gray nuclei, especially the striatum and the thalamus. Hypertension is the major cause of diffuse disease, and in many patients, both focal and diffuse disease are observed together. The 3 most common mechanisms of vascular dementia are multiple cortical infarcts, a strategic single infarct, and small vessel disease.

• #9 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets. […] Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis. […] Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. […] Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. In Binswanger disease, vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.

• #10 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets. […] Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis. […] Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. […] Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. In Binswanger disease, vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.

• #11 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets. […] Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis. […] Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. […] Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. In Binswanger disease, vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.

• #12 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets. […] Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis. […] Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. […] Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. In Binswanger disease, vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.

• #13 Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease | Molecular Neurodegeneration | Full Text

  https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00640-5

  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. […] In VCID, cerebral small vessel disease (cSVD) often affects arterioles, capillaries, and venules, where arteriolosclerosis and cerebral amyloid angiopathy (CAA) are major pathologies. […] 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.

• #14 Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease | Molecular Neurodegeneration | Full Text

  https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00640-5

  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. […] In VCID, cerebral small vessel disease (cSVD) often affects arterioles, capillaries, and venules, where arteriolosclerosis and cerebral amyloid angiopathy (CAA) are major pathologies. […] 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.

• #15 Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease | Molecular Neurodegeneration | Full Text

  https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00640-5

  The etiological mechanisms of cSVD can be summarized in the following four pathways: 1) hypoperfusion/hypoxia, 2) BBB dysregulation, 3) ISF/CSF drainage disturbances, and 4) vascular inflammation. Each of them is predicted to contribute independently and interactively to cSVD pathogenesis. […] Chronic cerebral hypoperfusion and subsequent intermittent hypoxia provoke oxidative stress, mitochondrial dysfunction, inflammation, and proteinopathy, leading to neurodegeneration. […] BBB dysregulation is causatively involved in cSVD symptoms. Notably, chronic cerebral hypoperfusion or hypoxia is a major factor causing BBB damage. […] Glymphatic impairment is predicted to stagnate ISF/CSF drainage and exacerbate brain accumulations of deleterious protein/cell debris, which eventually leads to cSVD-related cognitive impairment. […] Vascular inflammation is causatively or consequently involved in oxidative stress, vascular endothelial dysfunction, BBB damage, atherosclerotic plaque formation, narrowing of the lumen, and hemodynamic impairment, all of which eventually culminate in the development of cSVD.

• #16 Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease | Molecular Neurodegeneration | Full Text

  https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00640-5

  The etiological mechanisms of cSVD can be summarized in the following four pathways: 1) hypoperfusion/hypoxia, 2) BBB dysregulation, 3) ISF/CSF drainage disturbances, and 4) vascular inflammation. Each of them is predicted to contribute independently and interactively to cSVD pathogenesis. […] Chronic cerebral hypoperfusion and subsequent intermittent hypoxia provoke oxidative stress, mitochondrial dysfunction, inflammation, and proteinopathy, leading to neurodegeneration. […] BBB dysregulation is causatively involved in cSVD symptoms. Notably, chronic cerebral hypoperfusion or hypoxia is a major factor causing BBB damage. […] Glymphatic impairment is predicted to stagnate ISF/CSF drainage and exacerbate brain accumulations of deleterious protein/cell debris, which eventually leads to cSVD-related cognitive impairment. […] Vascular inflammation is causatively or consequently involved in oxidative stress, vascular endothelial dysfunction, BBB damage, atherosclerotic plaque formation, narrowing of the lumen, and hemodynamic impairment, all of which eventually culminate in the development of cSVD.

• #17 Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease | Molecular Neurodegeneration | Full Text

  https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00640-5

  The etiological mechanisms of cSVD can be summarized in the following four pathways: 1) hypoperfusion/hypoxia, 2) BBB dysregulation, 3) ISF/CSF drainage disturbances, and 4) vascular inflammation. Each of them is predicted to contribute independently and interactively to cSVD pathogenesis. […] Chronic cerebral hypoperfusion and subsequent intermittent hypoxia provoke oxidative stress, mitochondrial dysfunction, inflammation, and proteinopathy, leading to neurodegeneration. […] BBB dysregulation is causatively involved in cSVD symptoms. Notably, chronic cerebral hypoperfusion or hypoxia is a major factor causing BBB damage. […] Glymphatic impairment is predicted to stagnate ISF/CSF drainage and exacerbate brain accumulations of deleterious protein/cell debris, which eventually leads to cSVD-related cognitive impairment. […] Vascular inflammation is causatively or consequently involved in oxidative stress, vascular endothelial dysfunction, BBB damage, atherosclerotic plaque formation, narrowing of the lumen, and hemodynamic impairment, all of which eventually culminate in the development of cSVD.

• #18 Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease | Molecular Neurodegeneration | Full Text

  https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00640-5

  The etiological mechanisms of cSVD can be summarized in the following four pathways: 1) hypoperfusion/hypoxia, 2) BBB dysregulation, 3) ISF/CSF drainage disturbances, and 4) vascular inflammation. Each of them is predicted to contribute independently and interactively to cSVD pathogenesis. […] Chronic cerebral hypoperfusion and subsequent intermittent hypoxia provoke oxidative stress, mitochondrial dysfunction, inflammation, and proteinopathy, leading to neurodegeneration. […] BBB dysregulation is causatively involved in cSVD symptoms. Notably, chronic cerebral hypoperfusion or hypoxia is a major factor causing BBB damage. […] Glymphatic impairment is predicted to stagnate ISF/CSF drainage and exacerbate brain accumulations of deleterious protein/cell debris, which eventually leads to cSVD-related cognitive impairment. […] Vascular inflammation is causatively or consequently involved in oxidative stress, vascular endothelial dysfunction, BBB damage, atherosclerotic plaque formation, narrowing of the lumen, and hemodynamic impairment, all of which eventually culminate in the development of cSVD.

• #19 Pathophysiology and probable etiology of cerebral small vessel disease in vascular dementia and Alzheimer’s disease | Molecular Neurodegeneration | Full Text

  https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-023-00640-5

  The etiological mechanisms of cSVD can be summarized in the following four pathways: 1) hypoperfusion/hypoxia, 2) BBB dysregulation, 3) ISF/CSF drainage disturbances, and 4) vascular inflammation. Each of them is predicted to contribute independently and interactively to cSVD pathogenesis. […] Chronic cerebral hypoperfusion and subsequent intermittent hypoxia provoke oxidative stress, mitochondrial dysfunction, inflammation, and proteinopathy, leading to neurodegeneration. […] BBB dysregulation is causatively involved in cSVD symptoms. Notably, chronic cerebral hypoperfusion or hypoxia is a major factor causing BBB damage. […] Glymphatic impairment is predicted to stagnate ISF/CSF drainage and exacerbate brain accumulations of deleterious protein/cell debris, which eventually leads to cSVD-related cognitive impairment. […] Vascular inflammation is causatively or consequently involved in oxidative stress, vascular endothelial dysfunction, BBB damage, atherosclerotic plaque formation, narrowing of the lumen, and hemodynamic impairment, all of which eventually culminate in the development of cSVD.

• #20 Models and Mechanisms of Vascular Dementia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4631710/

  Vascular Dementia (VaD) is a progressive disease caused by reduced blood flow to the brain, and it affects cognitive abilities especially executive functioning. […] VaD can be caused by a reduced cerebral blood flow supplying the brain that may or may not be associated with a stroke. […] The underlying molecular pathology in VaD is not clearly understood. […] In VaD, chronic hypoperfusion and thromboembolic events, lead to a decrease in CBF, hypoxia, oxidative stress and trigger inflammatory responses. […] Hypoxia induced oxidative stress leads to mitochondrial dysfunction (and vice versa), neuronal damage and apoptosis via nitric oxide synthase (NOS) pathway, malondialdehyde content, release of reactive oxygen species and free radicals. […] The vicious cycle of oxidative stress, endothelial and microvascular dysfunction and inflammation exacerbate cerebral damage.

• #21 Models and Mechanisms of Vascular Dementia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4631710/

  Vascular Dementia (VaD) is a progressive disease caused by reduced blood flow to the brain, and it affects cognitive abilities especially executive functioning. […] VaD can be caused by a reduced cerebral blood flow supplying the brain that may or may not be associated with a stroke. […] The underlying molecular pathology in VaD is not clearly understood. […] In VaD, chronic hypoperfusion and thromboembolic events, lead to a decrease in CBF, hypoxia, oxidative stress and trigger inflammatory responses. […] Hypoxia induced oxidative stress leads to mitochondrial dysfunction (and vice versa), neuronal damage and apoptosis via nitric oxide synthase (NOS) pathway, malondialdehyde content, release of reactive oxygen species and free radicals. […] The vicious cycle of oxidative stress, endothelial and microvascular dysfunction and inflammation exacerbate cerebral damage.

• #22 Models and Mechanisms of Vascular Dementia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4631710/

  Vascular Dementia (VaD) is a progressive disease caused by reduced blood flow to the brain, and it affects cognitive abilities especially executive functioning. […] VaD can be caused by a reduced cerebral blood flow supplying the brain that may or may not be associated with a stroke. […] The underlying molecular pathology in VaD is not clearly understood. […] In VaD, chronic hypoperfusion and thromboembolic events, lead to a decrease in CBF, hypoxia, oxidative stress and trigger inflammatory responses. […] Hypoxia induced oxidative stress leads to mitochondrial dysfunction (and vice versa), neuronal damage and apoptosis via nitric oxide synthase (NOS) pathway, malondialdehyde content, release of reactive oxygen species and free radicals. […] The vicious cycle of oxidative stress, endothelial and microvascular dysfunction and inflammation exacerbate cerebral damage.

• #23 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. […] The term of VaD substantially means „disease with a cognitive impairment resulting from cerebrovascular disease and ischemic or hemorrhagic brain injury”. […] The cognitive impairment attributable to cerebrovascular disease is a rapidly escalating public health problem. […] Vascular cognitive impairment is not a regular pathogenetic entity. Multiple small thromboembolic strokes or strokes in strategic locations such as the thalamus, frontal lobe or temporal lobes may cause cognitive impairment and frequently occur without classical stroke-like symptoms. […] In VaD, the majority of patients instead present widespread microangiopathy-related cerebral damage, which is often clinically silent or is accompanied by unspecific neurological signs.

• #24 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  Several mechanisms may explain why patients affected by stroke are prone to develop dementia. […] One of the mechanism involved in ischemic VaD is under the control of large vessels disease (atherosclerosis, and other arteriopathies), however, impaired cerebral flow in the absence of infarct as consequence of arterial stenosis has been documented, although its clinical consequences remain to be fully investigated. […] Moreover, the alterations of small vessels play a role in causing damage to the cerebral tissue and are potentially responsible for the subsequent development of cognitive alterations. […] The most common types of diseases affecting cerebral microvessels are: arteriosclerosis, lipohyalinosis, cerebral amyloid angiopathy, basal ganglia calcification, CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy), other uncommon intracerebral vasculopathies.

• #25 Models and Mechanisms of Vascular Dementia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4631710/

  The neurovascular unit, a conceptual model that describes functional interactions and signaling between neurons, capillaries, and glia in the brain is dysregulated largely by the interplay between oxidative stress and inflammation resulting in increased BBB disruption, edema, neurovascular uncoupling, and neuronal damage. […] In VaD, WM damage arises primarily from demyelination that is attributed to hypoxia induced oligodendrocyte damage. […] While the VaD disease pathology has been studied to a certain extent and various factors leading to cognitive dysfunction identified, there is still wide scope in understanding the pathology and broader picture of disease mechanism.

• #26 Models and Mechanisms of Vascular Dementia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4631710/

  The neurovascular unit, a conceptual model that describes functional interactions and signaling between neurons, capillaries, and glia in the brain is dysregulated largely by the interplay between oxidative stress and inflammation resulting in increased BBB disruption, edema, neurovascular uncoupling, and neuronal damage. […] In VaD, WM damage arises primarily from demyelination that is attributed to hypoxia induced oligodendrocyte damage. […] While the VaD disease pathology has been studied to a certain extent and various factors leading to cognitive dysfunction identified, there is still wide scope in understanding the pathology and broader picture of disease mechanism.

• #27 Models and Mechanisms of Vascular Dementia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4631710/

  The neurovascular unit, a conceptual model that describes functional interactions and signaling between neurons, capillaries, and glia in the brain is dysregulated largely by the interplay between oxidative stress and inflammation resulting in increased BBB disruption, edema, neurovascular uncoupling, and neuronal damage. […] In VaD, WM damage arises primarily from demyelination that is attributed to hypoxia induced oligodendrocyte damage. […] While the VaD disease pathology has been studied to a certain extent and various factors leading to cognitive dysfunction identified, there is still wide scope in understanding the pathology and broader picture of disease mechanism.

• #28 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results of recent clinical and basic studies have suggested that vascular risk factors, such as hypertension and diabetes mellitus, affect the pathogenesis of dementia. […] Cerebrovascular damage due to vascular risk factors directly triggers vascular dementia, and it is becoming more apparent that vascular risk factors also increase the risk of neurodegenerative Alzheimers disease, which is associated with the accumulation of neurotoxic proteins in the brain. […] Accumulating evidence indicates that hypertension during middle age increases the risk of developing Alzheimers disease in later life. […] It was reported that these neuropathological features (i.e., senile plaques and NFTs) were increased in the postmortem brain tissues of hypertensive patients, suggesting a direct association between hypertension and the pathogenesis of Alzheimers disease.

• #29 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results of recent clinical and basic studies have suggested that vascular risk factors, such as hypertension and diabetes mellitus, affect the pathogenesis of dementia. […] Cerebrovascular damage due to vascular risk factors directly triggers vascular dementia, and it is becoming more apparent that vascular risk factors also increase the risk of neurodegenerative Alzheimers disease, which is associated with the accumulation of neurotoxic proteins in the brain. […] Accumulating evidence indicates that hypertension during middle age increases the risk of developing Alzheimers disease in later life. […] It was reported that these neuropathological features (i.e., senile plaques and NFTs) were increased in the postmortem brain tissues of hypertensive patients, suggesting a direct association between hypertension and the pathogenesis of Alzheimers disease.

• #30 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results of recent clinical and basic studies have suggested that vascular risk factors, such as hypertension and diabetes mellitus, affect the pathogenesis of dementia. […] Cerebrovascular damage due to vascular risk factors directly triggers vascular dementia, and it is becoming more apparent that vascular risk factors also increase the risk of neurodegenerative Alzheimers disease, which is associated with the accumulation of neurotoxic proteins in the brain. […] Accumulating evidence indicates that hypertension during middle age increases the risk of developing Alzheimers disease in later life. […] It was reported that these neuropathological features (i.e., senile plaques and NFTs) were increased in the postmortem brain tissues of hypertensive patients, suggesting a direct association between hypertension and the pathogenesis of Alzheimers disease.

• #31 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results of recent clinical and basic studies have suggested that vascular risk factors, such as hypertension and diabetes mellitus, affect the pathogenesis of dementia. […] Cerebrovascular damage due to vascular risk factors directly triggers vascular dementia, and it is becoming more apparent that vascular risk factors also increase the risk of neurodegenerative Alzheimers disease, which is associated with the accumulation of neurotoxic proteins in the brain. […] Accumulating evidence indicates that hypertension during middle age increases the risk of developing Alzheimers disease in later life. […] It was reported that these neuropathological features (i.e., senile plaques and NFTs) were increased in the postmortem brain tissues of hypertensive patients, suggesting a direct association between hypertension and the pathogenesis of Alzheimers disease.

• #32 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results from recent studies suggest a biological link between the dysregulation of the RAS and the pathogenesis of Alzheimers disease. […] A recent study also reported that hypertension exacerbates the vascular-damaging activity of A, suggesting that A plays a role in the development of hypertension-induced cerebrovascular disease and cognitive impairment. […] CAA may be a key player linking vascular risk factors, vascular dementia, and Alzheimers disease. […] The intensive management of vascular risk factors can be important in a patient with CAA in terms of dementia prevention.

• #33 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results from recent studies suggest a biological link between the dysregulation of the RAS and the pathogenesis of Alzheimers disease. […] A recent study also reported that hypertension exacerbates the vascular-damaging activity of A, suggesting that A plays a role in the development of hypertension-induced cerebrovascular disease and cognitive impairment. […] CAA may be a key player linking vascular risk factors, vascular dementia, and Alzheimers disease. […] The intensive management of vascular risk factors can be important in a patient with CAA in terms of dementia prevention.

• #34 New insights into the role of lifestyle-related diseases on vascular dementia and Alzheimer’s disease

  https://www.jstage.jst.go.jp/article/vascog/5/0/5_12/_html/-char/en

  However, a growing body of evidence from clinical and basic studies suggests that they have common molecular mechanisms. […] Whereas lifestyle-related diseases, such as hypertension, diabetes mellitus, and dyslipidemia, are well known to induce arteriosclerosis in cerebrovasculature and increase the risk of developing VaD, accumulating evidence suggests that these factors are also independent risk factors for AD. […] This implies a biological interplay among these pathological conditions. […] There seems to be a very complicated pathologic interaction in the brain, where VaD, AD, and lifestyle-related diseases mutually modify their biological mechanisms. […] Lifestyle-related diseases are associated with an increased number of dementia cases. […] Hypertension is the greatest risk factor for arteriosclerosis; the presence of hypertension in middle and old ages raises the relative risk for the development of VaD up to approximately 10 times.

• #35 New insights into the role of lifestyle-related diseases on vascular dementia and Alzheimer’s disease

  https://www.jstage.jst.go.jp/article/vascog/5/0/5_12/_html/-char/en

  Recent studies have shown that hypertension in midlife is associated with AD development later in life. […] Furthermore, the use of antihypertensive drugs is shown to reduce the incidence of dementia, including AD. […] It has been shown that diabetes mellitus increases the risk of CVD through arteriosclerosis, which leads to the development of VaD in later life. […] Importantly, impaired glucose tolerance, which is a very early stage of diabetes, is shown to increase the risk of developing VaD, suggesting that early detection and intervention of a glucose metabolism abnormality are very important for preventing VaD. […] Multiple studies have shown that diabetes mellitus significantly raises the risk of developing AD as well, which provides a new insight about biological mechanisms underlying AD.

• #36 New insights into the role of lifestyle-related diseases on vascular dementia and Alzheimer’s disease

  https://www.jstage.jst.go.jp/article/vascog/5/0/5_12/_html/-char/en

  Recent studies have shown that hypertension in midlife is associated with AD development later in life. […] Furthermore, the use of antihypertensive drugs is shown to reduce the incidence of dementia, including AD. […] It has been shown that diabetes mellitus increases the risk of CVD through arteriosclerosis, which leads to the development of VaD in later life. […] Importantly, impaired glucose tolerance, which is a very early stage of diabetes, is shown to increase the risk of developing VaD, suggesting that early detection and intervention of a glucose metabolism abnormality are very important for preventing VaD. […] Multiple studies have shown that diabetes mellitus significantly raises the risk of developing AD as well, which provides a new insight about biological mechanisms underlying AD.

• #37 New insights into the role of lifestyle-related diseases on vascular dementia and Alzheimer’s disease

  https://www.jstage.jst.go.jp/article/vascog/5/0/5_12/_html/-char/en

  Recent studies have shown that hypertension in midlife is associated with AD development later in life. […] Furthermore, the use of antihypertensive drugs is shown to reduce the incidence of dementia, including AD. […] It has been shown that diabetes mellitus increases the risk of CVD through arteriosclerosis, which leads to the development of VaD in later life. […] Importantly, impaired glucose tolerance, which is a very early stage of diabetes, is shown to increase the risk of developing VaD, suggesting that early detection and intervention of a glucose metabolism abnormality are very important for preventing VaD. […] Multiple studies have shown that diabetes mellitus significantly raises the risk of developing AD as well, which provides a new insight about biological mechanisms underlying AD.

• #38 New insights into the role of lifestyle-related diseases on vascular dementia and Alzheimer’s disease

  https://www.jstage.jst.go.jp/article/vascog/5/0/5_12/_html/-char/en

  The molecular mechanisms contributing to the beneficial effects of RAS modulation may be complex and pleiotropic. […] The association between diabetes mellitus and AD can partially be explained by cerebrovascular damage due to diabetes, which directly affects cognitive function. […] However, findings from clinical studies imply that the association exists independently of vascular factors, raising the possibility that diabetic conditions may have a direct impact on the pathogenesis of AD. […] Insulin potentially plays a role in the development of AD neuropathology. […] Takeda et al. explored a mechanistic link between diabetes mellitus and AD by establishing unique diabetic-AD mouse models. […] The diabetic-AD mice showed an early-onset cognitive impairment compared to the normal AD mouse model.

• #39 Vascular Dementia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430817/

  Vascular dementia is distinguished from other forms of MND in that it results from brain ischemia or hemorrhage and not from one or more underlying neurodegenerative proteinopathies. […] The pathogenesis of vascular dementia is understood as follows: vascular risk factors lead to cerebrovascular disease that, in turn, causes brain injury; the resulting disruption of cognitive networks culminates in vascular dementia. […] Neuropathologic studies illustrate vascular dementia’s high degree of heterogeneity, with multiple and overlapping types of cerebrovascular disease damaging multiple sites in the vascular tree. […] Cardiovascular risk factors for vascular dementia include smoking, hyperlipidemia, hypertension, diabetes, atrial fibrillation, obesity, and physical inactivity, among others.

• #40 Vascular Dementia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430817/

  A brief prcis of patterns of damage in the vascular tree that can result in cognitive impairment include: Atherosclerosis of large feeding arteries, often associated with smoking and hyperlipidemia, can cause territorial infarcts via cerebrovascular arterial occusion or thromboembolism, resulting in the classic „step-wise” cognitive and functional decline of vascular dementia. […] Arteriolosclerosis, mainly linked to hypertension, can cause occlusive disease of small arteries that feed deep, penetrating structures, leading to lacunar infarcts, central hemorrhage, and cerebral microbleeds. […] Microvascular disease, most closely associated with diabetes, commonly disrupts metabolic function at the capillary level. […] Finally, the APOE4 genotype and cerebral amyloid angiopathy (in which amyloid- accumulates primarily in pial and cortical arteries and capillaries, causing lobar hemorrhage, cortical microinfarcts, and white matter hyperintensities) are also risk factors for vascular cognitive impairment and dementia. […] Mixed vascular disease is more likely to cause cognitive and functional decline than pure atherosclerosis or arteriolosclerosis.

• #41 Vascular Dementia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430817/

  A brief prcis of patterns of damage in the vascular tree that can result in cognitive impairment include: Atherosclerosis of large feeding arteries, often associated with smoking and hyperlipidemia, can cause territorial infarcts via cerebrovascular arterial occusion or thromboembolism, resulting in the classic „step-wise” cognitive and functional decline of vascular dementia. […] Arteriolosclerosis, mainly linked to hypertension, can cause occlusive disease of small arteries that feed deep, penetrating structures, leading to lacunar infarcts, central hemorrhage, and cerebral microbleeds. […] Microvascular disease, most closely associated with diabetes, commonly disrupts metabolic function at the capillary level. […] Finally, the APOE4 genotype and cerebral amyloid angiopathy (in which amyloid- accumulates primarily in pial and cortical arteries and capillaries, causing lobar hemorrhage, cortical microinfarcts, and white matter hyperintensities) are also risk factors for vascular cognitive impairment and dementia. […] Mixed vascular disease is more likely to cause cognitive and functional decline than pure atherosclerosis or arteriolosclerosis.

• #42 Vascular Dementia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430817/

  A brief prcis of patterns of damage in the vascular tree that can result in cognitive impairment include: Atherosclerosis of large feeding arteries, often associated with smoking and hyperlipidemia, can cause territorial infarcts via cerebrovascular arterial occusion or thromboembolism, resulting in the classic „step-wise” cognitive and functional decline of vascular dementia. […] Arteriolosclerosis, mainly linked to hypertension, can cause occlusive disease of small arteries that feed deep, penetrating structures, leading to lacunar infarcts, central hemorrhage, and cerebral microbleeds. […] Microvascular disease, most closely associated with diabetes, commonly disrupts metabolic function at the capillary level. […] Finally, the APOE4 genotype and cerebral amyloid angiopathy (in which amyloid- accumulates primarily in pial and cortical arteries and capillaries, causing lobar hemorrhage, cortical microinfarcts, and white matter hyperintensities) are also risk factors for vascular cognitive impairment and dementia. […] Mixed vascular disease is more likely to cause cognitive and functional decline than pure atherosclerosis or arteriolosclerosis.

• #43 Emerging Biomarkers in Vascular Cognitive Impairment and Dementia: From Pathophysiological Pathways to Clinical Application

  https://www.mdpi.com/1422-0067/20/11/2812

  Inflammation has been recognized to have a crucial role in the pathogenic mechanisms of cerebrovascular and neurodegenerative diseases. […] Microvascular inflammation, as outlined previously, is a common feature of hypoperfusion models with markers of chronic inflammation and endothelial activation, leading to increased BBB permeability and to infiltration of inflammatory factors like interleukins (ILs), MMPs, Tumor necrosis factor (TNFα), toll-like receptor 4 (TLR4), C-reactive protein (CRP). […] Several other processes are promoted by inflammation and might contribute to the pathogenesis of VCID such as atherogenesis and platelet aggregation. […] The goal of diagnostic biomarkers development in VCID is to identify patients at early stage when treatment may be effective in blocking the progressive damage to the white matter. […] Given these premises, it is likely that a single biomarker might not be adequate to identify underlying complexities that are at the basis of cellular changes linked to VCID. […] The heterogeneity of CVD makes it challenging to elucidate the neuropathological substrates and mechanisms of VCID.

• #44 Emerging Biomarkers in Vascular Cognitive Impairment and Dementia: From Pathophysiological Pathways to Clinical Application

  https://www.mdpi.com/1422-0067/20/11/2812

  Inflammation has been recognized to have a crucial role in the pathogenic mechanisms of cerebrovascular and neurodegenerative diseases. […] Microvascular inflammation, as outlined previously, is a common feature of hypoperfusion models with markers of chronic inflammation and endothelial activation, leading to increased BBB permeability and to infiltration of inflammatory factors like interleukins (ILs), MMPs, Tumor necrosis factor (TNFα), toll-like receptor 4 (TLR4), C-reactive protein (CRP). […] Several other processes are promoted by inflammation and might contribute to the pathogenesis of VCID such as atherogenesis and platelet aggregation. […] The goal of diagnostic biomarkers development in VCID is to identify patients at early stage when treatment may be effective in blocking the progressive damage to the white matter. […] Given these premises, it is likely that a single biomarker might not be adequate to identify underlying complexities that are at the basis of cellular changes linked to VCID. […] The heterogeneity of CVD makes it challenging to elucidate the neuropathological substrates and mechanisms of VCID.

• #45 Influences and mechanism of erythropoietin on the cognitive function of vascular dementia rats | Aging

  https://www.aging-us.com/article/205178/text

  Purpose: To investigate the influences and mechanism of erythropoietin (EPO) on the cognitive function of vascular dementia (VD) rats. […] Vascular dementia (VD), a severe cognitive dysfunction syndrome, is defined as an ischemic or hemorrhagic cerebrovascular disease induced by chronic hypoperfusion under ischemia and hypoxia. […] Oxidative stress, as a main risk factor for the occurrence and development of VD, can lead to an imbalance of antioxidant active substances and reactive oxygen species (ROS), causing neuronal damage. […] EPO can effectively ameliorate the cognitive dysfunction induced by chronic hypoperfusion in VD rats by mediating oxidative stress-related pathways. […] EPO can regulate the oxidative stress in hippocampal neurons, thereby resisting apoptosis and inhibiting inflammatory response through the BDNF/TrKB/PI3K/ERK1/2 axis to effectively ameliorate the cognitive dysfunction caused by chronic hypoperfusion in VD rats.

• #46 Unravelling the Threads: A Brief Insight into Vascular Dementia

  https://www.mdpi.com/2813-2475/2/4/33

  Vascular dementia (VaD), characterized by cognitive decline attributable to cerebrovascular disease, is the second most common type of dementia after Alzheimer’s disease. […] VaD is a neurocognitive disorder characterized by a decline in cognitive functioning caused by diminished cerebral blood flow. This reduction in blood flow is frequently attributed to cerebrovascular incidents, such as stroke or a succession of minor strokes, which subsequently result in neuronal damage. […] The pathogenesis of VaD is also influenced by inflammatory processes. The occurrence of ischemia injury can be intensified and result in the long-term impairment of neurological function due to the release of pro-inflammatory cytokines. […] Extensive research has been conducted on the involvement of oxidative stress in the process of neurodegeneration in VaD. The production of free radicals during ischemia episodes has the potential to cause oxidative harm and ultimately result in the demise of neurons.

• #47 Unravelling the Threads: A Brief Insight into Vascular Dementia

  https://www.mdpi.com/2813-2475/2/4/33

  Vascular dementia (VaD), characterized by cognitive decline attributable to cerebrovascular disease, is the second most common type of dementia after Alzheimer’s disease. […] VaD is a neurocognitive disorder characterized by a decline in cognitive functioning caused by diminished cerebral blood flow. This reduction in blood flow is frequently attributed to cerebrovascular incidents, such as stroke or a succession of minor strokes, which subsequently result in neuronal damage. […] The pathogenesis of VaD is also influenced by inflammatory processes. The occurrence of ischemia injury can be intensified and result in the long-term impairment of neurological function due to the release of pro-inflammatory cytokines. […] Extensive research has been conducted on the involvement of oxidative stress in the process of neurodegeneration in VaD. The production of free radicals during ischemia episodes has the potential to cause oxidative harm and ultimately result in the demise of neurons.

• #48

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia closely related to cerebrovascular risk is increasing at an epidemic rate. […] Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. […] It is now becoming clear that synaptic dysfunction induced by CCH is one of the important pathogenic factors closely related to cognitive impairment in VD. […] Synaptic dysfunction in VD includes the change of morphological structure and functional state of the synapses. […] Mounting evidence suggests that NO and the NO/cGMP/cAMP-regulatory element binding (CREB) pathway are involved in synaptic plasticity and memory.

• #49

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  Nitric oxide is an essential, biological, intercellular messenger that conveys neuronal signal transmission in the central nervous system (CNS), and it represents the key molecule linking cerebrovascular and neuronal function. […] The pathogenesis of VD involves dysfunctions of synaptic neurons, endothelial cells, and microglia. […] It is well known that cerebral hypoperfusion is the main cause of VD. […] Synaptic dysfunction is mainly caused by the hypoperfusion associated with synaptic structure, function, and the alterations of the dendritic spine in post-mortem tissue in VD. […] Other reasons such as mitochondrial dysfunction, endoplasmic reticulum stress (ERS), neuroinflammation, and microglia activation in VD also lead to synaptic dysfunction. […] The hypoperfusion-mediated dysfunction of cerebrovascular endothelial cells leads to BBB damage, which further facilitates synaptic dysfunction and neuroinflammation.

• #50

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  The regulation of NO production seems more complex. […] In the early stages of stroke, owing to the rapid reduction of cerebral blood flow, the glucose and oxygen supply are dramatically reduced in the ischemic brain region along with Ca2+ overload. […] Membrane depolarization causes the release of excitotoxic amino acid glutamate and significantly decreased eNOS activity, along with the reduced secretion of NO and low bioavailability of NO. […] In summary, decreased production and increased consumption of NO because of hypoxia and ROS are closely associated with cognitive impairment in VD. […] It has been confirmed that the attenuation of eNOS activity can result in endothelial dysfunction in dementia, while, increasing the intake of exogenous NO can improve the cognition state in vascular cognitive impairment.

• #51

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  The regulation of NO production seems more complex. […] In the early stages of stroke, owing to the rapid reduction of cerebral blood flow, the glucose and oxygen supply are dramatically reduced in the ischemic brain region along with Ca2+ overload. […] Membrane depolarization causes the release of excitotoxic amino acid glutamate and significantly decreased eNOS activity, along with the reduced secretion of NO and low bioavailability of NO. […] In summary, decreased production and increased consumption of NO because of hypoxia and ROS are closely associated with cognitive impairment in VD. […] It has been confirmed that the attenuation of eNOS activity can result in endothelial dysfunction in dementia, while, increasing the intake of exogenous NO can improve the cognition state in vascular cognitive impairment.

• #52

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  The regulation of NO production seems more complex. […] In the early stages of stroke, owing to the rapid reduction of cerebral blood flow, the glucose and oxygen supply are dramatically reduced in the ischemic brain region along with Ca2+ overload. […] Membrane depolarization causes the release of excitotoxic amino acid glutamate and significantly decreased eNOS activity, along with the reduced secretion of NO and low bioavailability of NO. […] In summary, decreased production and increased consumption of NO because of hypoxia and ROS are closely associated with cognitive impairment in VD. […] It has been confirmed that the attenuation of eNOS activity can result in endothelial dysfunction in dementia, while, increasing the intake of exogenous NO can improve the cognition state in vascular cognitive impairment.

• #53 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. […] The precise mechanisms involved in VaD remain unclear, but accumulating evidence from various experimental cerebral ischemia models indicates that in addition to cholinergic deficiency, post-ischemic inflammation occurs in response to ischemic injury and contributes to delayed brain damage. […] More interestingly, cholinergic agents, including acetylcholinesterase (AChE) inhibitors, have shown considerable benefits in VaD therapy, and these effects were recently reported to be associated with the cholinergic anti-inflammatory pathway, suggesting that modulation of this pathway may provide a useful therapeutic strategy to ameliorate VaD.

• #54 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  The pathology of vascular cognitive disorder shows focal, multifocal or diffuse vascular and/or ischemic lesions involving various brain areas and neuronal networks, with deafferentation of frontal and limbic cortical structures and interruption of basal ganglia, thalamus, white matter and subfrontal areas. […] Cholinergic dysfunction which resembles that observed in patients with AD occurs due to a dense network of cholinergic fibers exists in the injured area. […] Many studies of cholinergic deficit in cerebral ischemia-related VaD models have shown persistent reductions in several cholinergic markers. […] It has been suggested that patients with VaD also exhibit cholinergic deficits. […] Inflammatory injury is another significant characteristic of VaD pathology. […] The concept of the cholinergic anti-inflammation pathway was proposed by Tracey and coworkers at the turn of the century.

• #55 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  The pathology of vascular cognitive disorder shows focal, multifocal or diffuse vascular and/or ischemic lesions involving various brain areas and neuronal networks, with deafferentation of frontal and limbic cortical structures and interruption of basal ganglia, thalamus, white matter and subfrontal areas. […] Cholinergic dysfunction which resembles that observed in patients with AD occurs due to a dense network of cholinergic fibers exists in the injured area. […] Many studies of cholinergic deficit in cerebral ischemia-related VaD models have shown persistent reductions in several cholinergic markers. […] It has been suggested that patients with VaD also exhibit cholinergic deficits. […] Inflammatory injury is another significant characteristic of VaD pathology. […] The concept of the cholinergic anti-inflammation pathway was proposed by Tracey and coworkers at the turn of the century.

• #56 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  The pathology of vascular cognitive disorder shows focal, multifocal or diffuse vascular and/or ischemic lesions involving various brain areas and neuronal networks, with deafferentation of frontal and limbic cortical structures and interruption of basal ganglia, thalamus, white matter and subfrontal areas. […] Cholinergic dysfunction which resembles that observed in patients with AD occurs due to a dense network of cholinergic fibers exists in the injured area. […] Many studies of cholinergic deficit in cerebral ischemia-related VaD models have shown persistent reductions in several cholinergic markers. […] It has been suggested that patients with VaD also exhibit cholinergic deficits. […] Inflammatory injury is another significant characteristic of VaD pathology. […] The concept of the cholinergic anti-inflammation pathway was proposed by Tracey and coworkers at the turn of the century.

• #57 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  The pathology of vascular cognitive disorder shows focal, multifocal or diffuse vascular and/or ischemic lesions involving various brain areas and neuronal networks, with deafferentation of frontal and limbic cortical structures and interruption of basal ganglia, thalamus, white matter and subfrontal areas. […] Cholinergic dysfunction which resembles that observed in patients with AD occurs due to a dense network of cholinergic fibers exists in the injured area. […] Many studies of cholinergic deficit in cerebral ischemia-related VaD models have shown persistent reductions in several cholinergic markers. […] It has been suggested that patients with VaD also exhibit cholinergic deficits. […] Inflammatory injury is another significant characteristic of VaD pathology. […] The concept of the cholinergic anti-inflammation pathway was proposed by Tracey and coworkers at the turn of the century.

• #58 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  The pathology of vascular cognitive disorder shows focal, multifocal or diffuse vascular and/or ischemic lesions involving various brain areas and neuronal networks, with deafferentation of frontal and limbic cortical structures and interruption of basal ganglia, thalamus, white matter and subfrontal areas. […] Cholinergic dysfunction which resembles that observed in patients with AD occurs due to a dense network of cholinergic fibers exists in the injured area. […] Many studies of cholinergic deficit in cerebral ischemia-related VaD models have shown persistent reductions in several cholinergic markers. […] It has been suggested that patients with VaD also exhibit cholinergic deficits. […] Inflammatory injury is another significant characteristic of VaD pathology. […] The concept of the cholinergic anti-inflammation pathway was proposed by Tracey and coworkers at the turn of the century.

• #59 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  The pathology of vascular cognitive disorder shows focal, multifocal or diffuse vascular and/or ischemic lesions involving various brain areas and neuronal networks, with deafferentation of frontal and limbic cortical structures and interruption of basal ganglia, thalamus, white matter and subfrontal areas. […] Cholinergic dysfunction which resembles that observed in patients with AD occurs due to a dense network of cholinergic fibers exists in the injured area. […] Many studies of cholinergic deficit in cerebral ischemia-related VaD models have shown persistent reductions in several cholinergic markers. […] It has been suggested that patients with VaD also exhibit cholinergic deficits. […] Inflammatory injury is another significant characteristic of VaD pathology. […] The concept of the cholinergic anti-inflammation pathway was proposed by Tracey and coworkers at the turn of the century.

• #60 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Recent work has shown that ACh released from cholinergic axon terminals can interact with 7 nicotinic ACh receptors (nAChRs) on vicinal immune cells. […] Therefore, cholinergic agents may ameliorate cerebral ischemia injury via their anti-inflammatory activity. […] Although the precise mechanisms by which huperzine A produced the above-mentioned preclinical and clinical effects remain unclear, our previous study indicated that the benefits of huperzine A may depend at least partly on the anti-inflammatory property. […] The therapeutic effects of huperzine A in VaD have been extensively evaluated and have consistently shown favorable outcomes. […] In fact, the effects of these AChE inhibitors have already been well evaluated in the treatment of VaD. […] The above-mentioned findings indicate that rivastigmine may influence central nervous system inflammation by up-regulating cholinergic function, which may contribute to its protective effects in VaD patients and animal models. […] These findings provide new insight into the pharmacological application of cholinergic functional enhancement accompanied by the adoption of the cholinergic anti-inflammation pathway.

• #61 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Recent work has shown that ACh released from cholinergic axon terminals can interact with 7 nicotinic ACh receptors (nAChRs) on vicinal immune cells. […] Therefore, cholinergic agents may ameliorate cerebral ischemia injury via their anti-inflammatory activity. […] Although the precise mechanisms by which huperzine A produced the above-mentioned preclinical and clinical effects remain unclear, our previous study indicated that the benefits of huperzine A may depend at least partly on the anti-inflammatory property. […] The therapeutic effects of huperzine A in VaD have been extensively evaluated and have consistently shown favorable outcomes. […] In fact, the effects of these AChE inhibitors have already been well evaluated in the treatment of VaD. […] The above-mentioned findings indicate that rivastigmine may influence central nervous system inflammation by up-regulating cholinergic function, which may contribute to its protective effects in VaD patients and animal models. […] These findings provide new insight into the pharmacological application of cholinergic functional enhancement accompanied by the adoption of the cholinergic anti-inflammation pathway.

• #62 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. […] The precise mechanisms involved in VaD remain unclear, but accumulating evidence from various experimental cerebral ischemia models indicates that in addition to cholinergic deficiency, post-ischemic inflammation occurs in response to ischemic injury and contributes to delayed brain damage. […] More interestingly, cholinergic agents, including acetylcholinesterase (AChE) inhibitors, have shown considerable benefits in VaD therapy, and these effects were recently reported to be associated with the cholinergic anti-inflammatory pathway, suggesting that modulation of this pathway may provide a useful therapeutic strategy to ameliorate VaD.

• #63 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Recent work has shown that ACh released from cholinergic axon terminals can interact with 7 nicotinic ACh receptors (nAChRs) on vicinal immune cells. […] Therefore, cholinergic agents may ameliorate cerebral ischemia injury via their anti-inflammatory activity. […] Although the precise mechanisms by which huperzine A produced the above-mentioned preclinical and clinical effects remain unclear, our previous study indicated that the benefits of huperzine A may depend at least partly on the anti-inflammatory property. […] The therapeutic effects of huperzine A in VaD have been extensively evaluated and have consistently shown favorable outcomes. […] In fact, the effects of these AChE inhibitors have already been well evaluated in the treatment of VaD. […] The above-mentioned findings indicate that rivastigmine may influence central nervous system inflammation by up-regulating cholinergic function, which may contribute to its protective effects in VaD patients and animal models. […] These findings provide new insight into the pharmacological application of cholinergic functional enhancement accompanied by the adoption of the cholinergic anti-inflammation pathway.

• #64 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Recent work has shown that ACh released from cholinergic axon terminals can interact with 7 nicotinic ACh receptors (nAChRs) on vicinal immune cells. […] Therefore, cholinergic agents may ameliorate cerebral ischemia injury via their anti-inflammatory activity. […] Although the precise mechanisms by which huperzine A produced the above-mentioned preclinical and clinical effects remain unclear, our previous study indicated that the benefits of huperzine A may depend at least partly on the anti-inflammatory property. […] The therapeutic effects of huperzine A in VaD have been extensively evaluated and have consistently shown favorable outcomes. […] In fact, the effects of these AChE inhibitors have already been well evaluated in the treatment of VaD. […] The above-mentioned findings indicate that rivastigmine may influence central nervous system inflammation by up-regulating cholinergic function, which may contribute to its protective effects in VaD patients and animal models. […] These findings provide new insight into the pharmacological application of cholinergic functional enhancement accompanied by the adoption of the cholinergic anti-inflammation pathway.

• #65 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Recent work has shown that ACh released from cholinergic axon terminals can interact with 7 nicotinic ACh receptors (nAChRs) on vicinal immune cells. […] Therefore, cholinergic agents may ameliorate cerebral ischemia injury via their anti-inflammatory activity. […] Although the precise mechanisms by which huperzine A produced the above-mentioned preclinical and clinical effects remain unclear, our previous study indicated that the benefits of huperzine A may depend at least partly on the anti-inflammatory property. […] The therapeutic effects of huperzine A in VaD have been extensively evaluated and have consistently shown favorable outcomes. […] In fact, the effects of these AChE inhibitors have already been well evaluated in the treatment of VaD. […] The above-mentioned findings indicate that rivastigmine may influence central nervous system inflammation by up-regulating cholinergic function, which may contribute to its protective effects in VaD patients and animal models. […] These findings provide new insight into the pharmacological application of cholinergic functional enhancement accompanied by the adoption of the cholinergic anti-inflammation pathway.

• #66 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Recent work has shown that ACh released from cholinergic axon terminals can interact with 7 nicotinic ACh receptors (nAChRs) on vicinal immune cells. […] Therefore, cholinergic agents may ameliorate cerebral ischemia injury via their anti-inflammatory activity. […] Although the precise mechanisms by which huperzine A produced the above-mentioned preclinical and clinical effects remain unclear, our previous study indicated that the benefits of huperzine A may depend at least partly on the anti-inflammatory property. […] The therapeutic effects of huperzine A in VaD have been extensively evaluated and have consistently shown favorable outcomes. […] In fact, the effects of these AChE inhibitors have already been well evaluated in the treatment of VaD. […] The above-mentioned findings indicate that rivastigmine may influence central nervous system inflammation by up-regulating cholinergic function, which may contribute to its protective effects in VaD patients and animal models. […] These findings provide new insight into the pharmacological application of cholinergic functional enhancement accompanied by the adoption of the cholinergic anti-inflammation pathway.

• #67 Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment | Acta Pharmacologica Sinica

  https://www.nature.com/articles/aps200982

  Recent work has shown that ACh released from cholinergic axon terminals can interact with 7 nicotinic ACh receptors (nAChRs) on vicinal immune cells. […] Therefore, cholinergic agents may ameliorate cerebral ischemia injury via their anti-inflammatory activity. […] Although the precise mechanisms by which huperzine A produced the above-mentioned preclinical and clinical effects remain unclear, our previous study indicated that the benefits of huperzine A may depend at least partly on the anti-inflammatory property. […] The therapeutic effects of huperzine A in VaD have been extensively evaluated and have consistently shown favorable outcomes. […] In fact, the effects of these AChE inhibitors have already been well evaluated in the treatment of VaD. […] The above-mentioned findings indicate that rivastigmine may influence central nervous system inflammation by up-regulating cholinergic function, which may contribute to its protective effects in VaD patients and animal models. […] These findings provide new insight into the pharmacological application of cholinergic functional enhancement accompanied by the adoption of the cholinergic anti-inflammation pathway.

• #68 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The pathogenesis of white matter changes (WMC) is not well established and a number of possible mechanisms have been hypothesized, all mechanisms are reconducible to a form of cerebrovascular disease. […] The understanding of the pathobiology of AD and VaD received an impulse by the discovery of genes that produce monogenic forms of the illness or contribute to polygenic forms; in particular, the identification of genes contributing to VCI would no doubt provide insight into the cellular and molecular basis of VCI. […] Genetic factors play an important role in the aetiology of VaD, in particular, it’s seems to be more important in large-vessel stroke and small vessel stroke than in cryptogenic stroke, and there is no epidemiological evidence for a genetic component in cardioembolic stroke.

• #69 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The genes underlying VaD must be of 2 nonmutually exclusive classes: (1) genes that predispose individuals to cerebrovascular disease, and (2) genes that determine tissue responses to cerebrovascular disease (eg, genes conveying ischemic tolerance or susceptibility, or the ability to recover from ischemic insult). […] The CADASIL condition is a heritable small-vessel disease caused by mutations in NOTCH3 gene which is normally expressed in vascular smooth muscle cells and pericytes (including those of the cerebral vasculature) and that encodes a cell-surface receptor, which has a role in arterial development and is expressed on vascular smooth-muscle cells. […] The small vessel alterations could also lead to damage affecting the blood-brain barrier and chronic leakage of fluid and macromolecules in the white matter, even if the neuroimaging methods do not detect diffuse alterations of the blood-brain barrier in vivo.

• #70 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The genes underlying VaD must be of 2 nonmutually exclusive classes: (1) genes that predispose individuals to cerebrovascular disease, and (2) genes that determine tissue responses to cerebrovascular disease (eg, genes conveying ischemic tolerance or susceptibility, or the ability to recover from ischemic insult). […] The CADASIL condition is a heritable small-vessel disease caused by mutations in NOTCH3 gene which is normally expressed in vascular smooth muscle cells and pericytes (including those of the cerebral vasculature) and that encodes a cell-surface receptor, which has a role in arterial development and is expressed on vascular smooth-muscle cells. […] The small vessel alterations could also lead to damage affecting the blood-brain barrier and chronic leakage of fluid and macromolecules in the white matter, even if the neuroimaging methods do not detect diffuse alterations of the blood-brain barrier in vivo.

• #71 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The genes underlying VaD must be of 2 nonmutually exclusive classes: (1) genes that predispose individuals to cerebrovascular disease, and (2) genes that determine tissue responses to cerebrovascular disease (eg, genes conveying ischemic tolerance or susceptibility, or the ability to recover from ischemic insult). […] The CADASIL condition is a heritable small-vessel disease caused by mutations in NOTCH3 gene which is normally expressed in vascular smooth muscle cells and pericytes (including those of the cerebral vasculature) and that encodes a cell-surface receptor, which has a role in arterial development and is expressed on vascular smooth-muscle cells. […] The small vessel alterations could also lead to damage affecting the blood-brain barrier and chronic leakage of fluid and macromolecules in the white matter, even if the neuroimaging methods do not detect diffuse alterations of the blood-brain barrier in vivo.

• #72 Discovery of Mechanism behind Vascular Dementia Could Help Develop Treatments | Inside Precision Medicine

  https://www.insideprecisionmedicine.com/news-and-features/discovery-of-mechanism-behind-vascular-dementia-could-help-develop-treatments/

  Research led by the University of Vermont shines a light on the mechanism behind vascular dementia in a mouse model, which the investigators hope will lead to better treatments being developed for the neurodegenerative condition. […] As reported in the journal PNAS, reduced blood flow to the brain is known to be a key factor in the hypertension-induced vascular dementia disease process, but the mechanism behind this was unclear, making it difficult to design therapies to improve blood flow. […] The current study investigated this mechanism in model mice and found the reduced cerebral blood flow was caused by a part of the smooth muscle cells becoming separated from the plasma membrane leading to a breakdown in cell signaling that would lead to the blood vessels relaxing under normal circumstances.

• #73 Discovery of Mechanism behind Vascular Dementia Could Help Develop Treatments | Inside Precision Medicine

  https://www.insideprecisionmedicine.com/news-and-features/discovery-of-mechanism-behind-vascular-dementia-could-help-develop-treatments/

  Research led by the University of Vermont shines a light on the mechanism behind vascular dementia in a mouse model, which the investigators hope will lead to better treatments being developed for the neurodegenerative condition. […] As reported in the journal PNAS, reduced blood flow to the brain is known to be a key factor in the hypertension-induced vascular dementia disease process, but the mechanism behind this was unclear, making it difficult to design therapies to improve blood flow. […] The current study investigated this mechanism in model mice and found the reduced cerebral blood flow was caused by a part of the smooth muscle cells becoming separated from the plasma membrane leading to a breakdown in cell signaling that would lead to the blood vessels relaxing under normal circumstances.

• #74 Discovery of Mechanism behind Vascular Dementia Could Help Develop Treatments | Inside Precision Medicine

  https://www.insideprecisionmedicine.com/news-and-features/discovery-of-mechanism-behind-vascular-dementia-could-help-develop-treatments/

  To try and understand the mechanism behind hypertension-triggered vascular dementia better, Mark Nelson, a professor at the University of Vermont, and colleagues at the University of Manchester in the U.K. used a mouse model (BPH/2) of hypertension and vascular dementia to study the physiological mechanism behind the condition. […] Using a combination of techniques, the team found that the arteries in the brains of the mice were constricted, because a part of the smooth muscle cell known as the sarcoplasmic reticulum had separated from the plasma membrane. This separation stopped calcium signals that would normally trigger relaxation of the blood vessels from reaching their potassium channel targets. […] By uncovering how high blood pressure causes arteries in the brain to remain constricted, our research reveals a new avenue for drug discovery that may help to find the first treatment for vascular dementia. Allowing blood to return as normal to damaged areas of the brain will be crucial to stopping this devastating condition in its tracks.

• #75 Discovery of Mechanism behind Vascular Dementia Could Help Develop Treatments | Inside Precision Medicine

  https://www.insideprecisionmedicine.com/news-and-features/discovery-of-mechanism-behind-vascular-dementia-could-help-develop-treatments/

  To try and understand the mechanism behind hypertension-triggered vascular dementia better, Mark Nelson, a professor at the University of Vermont, and colleagues at the University of Manchester in the U.K. used a mouse model (BPH/2) of hypertension and vascular dementia to study the physiological mechanism behind the condition. […] Using a combination of techniques, the team found that the arteries in the brains of the mice were constricted, because a part of the smooth muscle cell known as the sarcoplasmic reticulum had separated from the plasma membrane. This separation stopped calcium signals that would normally trigger relaxation of the blood vessels from reaching their potassium channel targets. […] By uncovering how high blood pressure causes arteries in the brain to remain constricted, our research reveals a new avenue for drug discovery that may help to find the first treatment for vascular dementia. Allowing blood to return as normal to damaged areas of the brain will be crucial to stopping this devastating condition in its tracks.

• #76 Discovery of Mechanism behind Vascular Dementia Could Help Develop Treatments | Inside Precision Medicine

  https://www.insideprecisionmedicine.com/news-and-features/discovery-of-mechanism-behind-vascular-dementia-could-help-develop-treatments/

  To try and understand the mechanism behind hypertension-triggered vascular dementia better, Mark Nelson, a professor at the University of Vermont, and colleagues at the University of Manchester in the U.K. used a mouse model (BPH/2) of hypertension and vascular dementia to study the physiological mechanism behind the condition. […] Using a combination of techniques, the team found that the arteries in the brains of the mice were constricted, because a part of the smooth muscle cell known as the sarcoplasmic reticulum had separated from the plasma membrane. This separation stopped calcium signals that would normally trigger relaxation of the blood vessels from reaching their potassium channel targets. […] By uncovering how high blood pressure causes arteries in the brain to remain constricted, our research reveals a new avenue for drug discovery that may help to find the first treatment for vascular dementia. Allowing blood to return as normal to damaged areas of the brain will be crucial to stopping this devastating condition in its tracks.

• #77 New Cause of Alzheimer’s Disease and Vascular Dementia Discovered | Sci.News

  https://www.sci.news/othersciences/neuroscience/ferroptosis-alzheimers-disease-vascular-dementia-12242.html

  Ferroptosis, which is caused by a buildup of iron in cells, appears to be a major mechanism of white matter injury in Alzheimers disease and vascular dementia, according to a new study. […] The scientists found that the cascading effect of degenerating microglia appears to be a mechanism in advancing cognitive decline in Alzheimers disease and vascular dementia. […] The underlying cause initiating the cycle of decline likely relates to repeated episodes of low blood flow and oxygen delivery to the brain over time due to acute stroke or chronic conditions such as hypertension and diabetes.

• #78 New Cause of Alzheimer’s Disease and Vascular Dementia Discovered | Sci.News

  https://www.sci.news/othersciences/neuroscience/ferroptosis-alzheimers-disease-vascular-dementia-12242.html

  Ferroptosis, which is caused by a buildup of iron in cells, appears to be a major mechanism of white matter injury in Alzheimers disease and vascular dementia, according to a new study. […] The scientists found that the cascading effect of degenerating microglia appears to be a mechanism in advancing cognitive decline in Alzheimers disease and vascular dementia. […] The underlying cause initiating the cycle of decline likely relates to repeated episodes of low blood flow and oxygen delivery to the brain over time due to acute stroke or chronic conditions such as hypertension and diabetes.

• #79 New Cause of Alzheimer’s Disease and Vascular Dementia Discovered | Sci.News

  https://www.sci.news/othersciences/neuroscience/ferroptosis-alzheimers-disease-vascular-dementia-12242.html

  Ferroptosis, which is caused by a buildup of iron in cells, appears to be a major mechanism of white matter injury in Alzheimers disease and vascular dementia, according to a new study. […] The scientists found that the cascading effect of degenerating microglia appears to be a mechanism in advancing cognitive decline in Alzheimers disease and vascular dementia. […] The underlying cause initiating the cycle of decline likely relates to repeated episodes of low blood flow and oxygen delivery to the brain over time due to acute stroke or chronic conditions such as hypertension and diabetes.

• #80 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250108/Study-links-glymphatic-system-damage-to-vascular-dementia.aspx

  A new study from the Keck School of Medicine of USC has tested a biomarker linked to vascular dementia across four separate groups and proposed an explanation for how cognitive impairment arises. […] The condition is usually caused by cerebral small vessel disease (cSVD), which damages the brain’s small blood vessels-but researchers don’t yet know the exact mechanism linking cSVD to dementia. One theory involves problems with the glymphatic system, which helps clear waste from the brain. […] The study confirmed that a low DTI-ALPS score is a biomarker for cSVD and suggests that glymphatic damage may be driving cognitive decline. […] Wang and his team also analyzed the progression of symptoms across study participants, finding a possible pathway to explain how glymphatic problems lead to cognitive impairment.

• #81 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250108/Study-links-glymphatic-system-damage-to-vascular-dementia.aspx

  A new study from the Keck School of Medicine of USC has tested a biomarker linked to vascular dementia across four separate groups and proposed an explanation for how cognitive impairment arises. […] The condition is usually caused by cerebral small vessel disease (cSVD), which damages the brain’s small blood vessels-but researchers don’t yet know the exact mechanism linking cSVD to dementia. One theory involves problems with the glymphatic system, which helps clear waste from the brain. […] The study confirmed that a low DTI-ALPS score is a biomarker for cSVD and suggests that glymphatic damage may be driving cognitive decline. […] Wang and his team also analyzed the progression of symptoms across study participants, finding a possible pathway to explain how glymphatic problems lead to cognitive impairment.

• #82 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250108/Study-links-glymphatic-system-damage-to-vascular-dementia.aspx

  A new study from the Keck School of Medicine of USC has tested a biomarker linked to vascular dementia across four separate groups and proposed an explanation for how cognitive impairment arises. […] The condition is usually caused by cerebral small vessel disease (cSVD), which damages the brain’s small blood vessels-but researchers don’t yet know the exact mechanism linking cSVD to dementia. One theory involves problems with the glymphatic system, which helps clear waste from the brain. […] The study confirmed that a low DTI-ALPS score is a biomarker for cSVD and suggests that glymphatic damage may be driving cognitive decline. […] Wang and his team also analyzed the progression of symptoms across study participants, finding a possible pathway to explain how glymphatic problems lead to cognitive impairment.

• #83 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250108/Study-links-glymphatic-system-damage-to-vascular-dementia.aspx

  To find out more, the researchers conducted a mediation analysis, which studies the process or mechanism connecting two or more variables. In this case, they found that another biomarker-„free water” or excess water in the brain’s white matter-helped explain the link between glymphatic problems and cognitive decline. […] In this potential pathway, „first waste clearance is impaired, which causes accumulation of free water in the brain’s white matter. That leads to tissue damage and eventually to cognitive impairment,” said the paper’s first author, Xiaodan Liu, MD, PhD. […] But the team’s findings indicate that the DTI-ALPS score biomarker for vascular dementia is robust and ready to be used in clinical trials, Wang said. […] Those studies could explore enhancing glymphatic function as a way to treat vascular dementia.

• #84 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250108/Study-links-glymphatic-system-damage-to-vascular-dementia.aspx

  To find out more, the researchers conducted a mediation analysis, which studies the process or mechanism connecting two or more variables. In this case, they found that another biomarker-„free water” or excess water in the brain’s white matter-helped explain the link between glymphatic problems and cognitive decline. […] In this potential pathway, „first waste clearance is impaired, which causes accumulation of free water in the brain’s white matter. That leads to tissue damage and eventually to cognitive impairment,” said the paper’s first author, Xiaodan Liu, MD, PhD. […] But the team’s findings indicate that the DTI-ALPS score biomarker for vascular dementia is robust and ready to be used in clinical trials, Wang said. […] Those studies could explore enhancing glymphatic function as a way to treat vascular dementia.

• #85 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250108/Study-links-glymphatic-system-damage-to-vascular-dementia.aspx

  To find out more, the researchers conducted a mediation analysis, which studies the process or mechanism connecting two or more variables. In this case, they found that another biomarker-„free water” or excess water in the brain’s white matter-helped explain the link between glymphatic problems and cognitive decline. […] In this potential pathway, „first waste clearance is impaired, which causes accumulation of free water in the brain’s white matter. That leads to tissue damage and eventually to cognitive impairment,” said the paper’s first author, Xiaodan Liu, MD, PhD. […] But the team’s findings indicate that the DTI-ALPS score biomarker for vascular dementia is robust and ready to be used in clinical trials, Wang said. […] Those studies could explore enhancing glymphatic function as a way to treat vascular dementia.

• #86 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20250108/Study-links-glymphatic-system-damage-to-vascular-dementia.aspx

  To find out more, the researchers conducted a mediation analysis, which studies the process or mechanism connecting two or more variables. In this case, they found that another biomarker-„free water” or excess water in the brain’s white matter-helped explain the link between glymphatic problems and cognitive decline. […] In this potential pathway, „first waste clearance is impaired, which causes accumulation of free water in the brain’s white matter. That leads to tissue damage and eventually to cognitive impairment,” said the paper’s first author, Xiaodan Liu, MD, PhD. […] But the team’s findings indicate that the DTI-ALPS score biomarker for vascular dementia is robust and ready to be used in clinical trials, Wang said. […] Those studies could explore enhancing glymphatic function as a way to treat vascular dementia.

• #87 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. […] The term of VaD substantially means „disease with a cognitive impairment resulting from cerebrovascular disease and ischemic or hemorrhagic brain injury”. […] The cognitive impairment attributable to cerebrovascular disease is a rapidly escalating public health problem. […] Vascular cognitive impairment is not a regular pathogenetic entity. Multiple small thromboembolic strokes or strokes in strategic locations such as the thalamus, frontal lobe or temporal lobes may cause cognitive impairment and frequently occur without classical stroke-like symptoms. […] In VaD, the majority of patients instead present widespread microangiopathy-related cerebral damage, which is often clinically silent or is accompanied by unspecific neurological signs.

• #88 Pathophysiology of vascular dementia | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/1742-4933-6-13

  The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. […] The term of VaD substantially means „disease with a cognitive impairment resulting from cerebrovascular disease and ischemic or hemorrhagic brain injury”. […] The cognitive impairment attributable to cerebrovascular disease is a rapidly escalating public health problem. […] Vascular cognitive impairment is not a regular pathogenetic entity. Multiple small thromboembolic strokes or strokes in strategic locations such as the thalamus, frontal lobe or temporal lobes may cause cognitive impairment and frequently occur without classical stroke-like symptoms. […] In VaD, the majority of patients instead present widespread microangiopathy-related cerebral damage, which is often clinically silent or is accompanied by unspecific neurological signs.

• #89

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia closely related to cerebrovascular risk is increasing at an epidemic rate. […] Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. […] It is now becoming clear that synaptic dysfunction induced by CCH is one of the important pathogenic factors closely related to cognitive impairment in VD. […] Synaptic dysfunction in VD includes the change of morphological structure and functional state of the synapses. […] Mounting evidence suggests that NO and the NO/cGMP/cAMP-regulatory element binding (CREB) pathway are involved in synaptic plasticity and memory.

• #90

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia closely related to cerebrovascular risk is increasing at an epidemic rate. […] Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. […] It is now becoming clear that synaptic dysfunction induced by CCH is one of the important pathogenic factors closely related to cognitive impairment in VD. […] Synaptic dysfunction in VD includes the change of morphological structure and functional state of the synapses. […] Mounting evidence suggests that NO and the NO/cGMP/cAMP-regulatory element binding (CREB) pathway are involved in synaptic plasticity and memory.

• #91

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  Nitric oxide is an essential, biological, intercellular messenger that conveys neuronal signal transmission in the central nervous system (CNS), and it represents the key molecule linking cerebrovascular and neuronal function. […] The pathogenesis of VD involves dysfunctions of synaptic neurons, endothelial cells, and microglia. […] It is well known that cerebral hypoperfusion is the main cause of VD. […] Synaptic dysfunction is mainly caused by the hypoperfusion associated with synaptic structure, function, and the alterations of the dendritic spine in post-mortem tissue in VD. […] Other reasons such as mitochondrial dysfunction, endoplasmic reticulum stress (ERS), neuroinflammation, and microglia activation in VD also lead to synaptic dysfunction. […] The hypoperfusion-mediated dysfunction of cerebrovascular endothelial cells leads to BBB damage, which further facilitates synaptic dysfunction and neuroinflammation.

• #92

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  Nitric oxide is an essential, biological, intercellular messenger that conveys neuronal signal transmission in the central nervous system (CNS), and it represents the key molecule linking cerebrovascular and neuronal function. […] The pathogenesis of VD involves dysfunctions of synaptic neurons, endothelial cells, and microglia. […] It is well known that cerebral hypoperfusion is the main cause of VD. […] Synaptic dysfunction is mainly caused by the hypoperfusion associated with synaptic structure, function, and the alterations of the dendritic spine in post-mortem tissue in VD. […] Other reasons such as mitochondrial dysfunction, endoplasmic reticulum stress (ERS), neuroinflammation, and microglia activation in VD also lead to synaptic dysfunction. […] The hypoperfusion-mediated dysfunction of cerebrovascular endothelial cells leads to BBB damage, which further facilitates synaptic dysfunction and neuroinflammation.

• #93

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  Nitric oxide is an essential, biological, intercellular messenger that conveys neuronal signal transmission in the central nervous system (CNS), and it represents the key molecule linking cerebrovascular and neuronal function. […] The pathogenesis of VD involves dysfunctions of synaptic neurons, endothelial cells, and microglia. […] It is well known that cerebral hypoperfusion is the main cause of VD. […] Synaptic dysfunction is mainly caused by the hypoperfusion associated with synaptic structure, function, and the alterations of the dendritic spine in post-mortem tissue in VD. […] Other reasons such as mitochondrial dysfunction, endoplasmic reticulum stress (ERS), neuroinflammation, and microglia activation in VD also lead to synaptic dysfunction. […] The hypoperfusion-mediated dysfunction of cerebrovascular endothelial cells leads to BBB damage, which further facilitates synaptic dysfunction and neuroinflammation.

• #94

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  Nitric oxide is an essential, biological, intercellular messenger that conveys neuronal signal transmission in the central nervous system (CNS), and it represents the key molecule linking cerebrovascular and neuronal function. […] The pathogenesis of VD involves dysfunctions of synaptic neurons, endothelial cells, and microglia. […] It is well known that cerebral hypoperfusion is the main cause of VD. […] Synaptic dysfunction is mainly caused by the hypoperfusion associated with synaptic structure, function, and the alterations of the dendritic spine in post-mortem tissue in VD. […] Other reasons such as mitochondrial dysfunction, endoplasmic reticulum stress (ERS), neuroinflammation, and microglia activation in VD also lead to synaptic dysfunction. […] The hypoperfusion-mediated dysfunction of cerebrovascular endothelial cells leads to BBB damage, which further facilitates synaptic dysfunction and neuroinflammation.

• #95

  https://journals.lww.com/nrronline/fulltext/2025/02000/the_emerging_role_of_nitric_oxide_in_the_synaptic.9.aspx

  Nitric oxide is an essential, biological, intercellular messenger that conveys neuronal signal transmission in the central nervous system (CNS), and it represents the key molecule linking cerebrovascular and neuronal function. […] The pathogenesis of VD involves dysfunctions of synaptic neurons, endothelial cells, and microglia. […] It is well known that cerebral hypoperfusion is the main cause of VD. […] Synaptic dysfunction is mainly caused by the hypoperfusion associated with synaptic structure, function, and the alterations of the dendritic spine in post-mortem tissue in VD. […] Other reasons such as mitochondrial dysfunction, endoplasmic reticulum stress (ERS), neuroinflammation, and microglia activation in VD also lead to synaptic dysfunction. […] The hypoperfusion-mediated dysfunction of cerebrovascular endothelial cells leads to BBB damage, which further facilitates synaptic dysfunction and neuroinflammation.

• #96 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In cerebral amyloid angiopathy associated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. […] Prevalence of cerebral amyloid angiopathy is consistently higher in patients with dementia than in patients without dementia, which indicates its significant role in the pathogenesis of dementia. […] Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia. […] Several recent studies also suggest that the risk of developing Alzheimer disease is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. […] One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert.

• #97 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In cerebral amyloid angiopathy associated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. […] Prevalence of cerebral amyloid angiopathy is consistently higher in patients with dementia than in patients without dementia, which indicates its significant role in the pathogenesis of dementia. […] Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia. […] Several recent studies also suggest that the risk of developing Alzheimer disease is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. […] One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert.

• #98 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In cerebral amyloid angiopathy associated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. […] Prevalence of cerebral amyloid angiopathy is consistently higher in patients with dementia than in patients without dementia, which indicates its significant role in the pathogenesis of dementia. […] Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia. […] Several recent studies also suggest that the risk of developing Alzheimer disease is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. […] One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert.

• #99 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In cerebral amyloid angiopathy associated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. […] Prevalence of cerebral amyloid angiopathy is consistently higher in patients with dementia than in patients without dementia, which indicates its significant role in the pathogenesis of dementia. […] Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia. […] Several recent studies also suggest that the risk of developing Alzheimer disease is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. […] One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert.

• #100 Vascular Dementia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/292105-overview

  In cerebral amyloid angiopathy associated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. […] Prevalence of cerebral amyloid angiopathy is consistently higher in patients with dementia than in patients without dementia, which indicates its significant role in the pathogenesis of dementia. […] Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia. […] Several recent studies also suggest that the risk of developing Alzheimer disease is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. […] One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert.

• #101 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results from recent studies suggest a biological link between the dysregulation of the RAS and the pathogenesis of Alzheimers disease. […] A recent study also reported that hypertension exacerbates the vascular-damaging activity of A, suggesting that A plays a role in the development of hypertension-induced cerebrovascular disease and cognitive impairment. […] CAA may be a key player linking vascular risk factors, vascular dementia, and Alzheimers disease. […] The intensive management of vascular risk factors can be important in a patient with CAA in terms of dementia prevention.

• #102 Roles of vascular risk factors in the pathogenesis of dementia | Hypertension Research

  https://www.nature.com/articles/s41440-019-0357-9

  The results from recent studies suggest a biological link between the dysregulation of the RAS and the pathogenesis of Alzheimers disease. […] A recent study also reported that hypertension exacerbates the vascular-damaging activity of A, suggesting that A plays a role in the development of hypertension-induced cerebrovascular disease and cognitive impairment. […] CAA may be a key player linking vascular risk factors, vascular dementia, and Alzheimers disease. […] The intensive management of vascular risk factors can be important in a patient with CAA in terms of dementia prevention.

• #103 New insights into the role of lifestyle-related diseases on vascular dementia and Alzheimer’s disease

  https://www.jstage.jst.go.jp/article/vascog/5/0/5_12/_html/-char/en

  Studies using AD animal models show that diabetes mellitus and hypertension can increase the production rate of A in the brain or impair the clearance mechanism of A from the brain, both leading to A plaque formation. […] A aggregates are known to accumulate not only in the brain parenchyma but also in the cerebral blood vessels (cerebral amyloid angiopathy [CAA]). […] Recent studies also report that the vascular-damaging activity of A becomes more evident in the presence of hypertension. […] This suggests that AD-related A plays a role in the development of hypertension-induced CVD. […] CAA may be a key player linking lifestyle-related diseases, VaD, and AD. […] CAA is often accompanied by multiple cerebral microbleeds and is also known to contribute to the pathogenesis of VaD. […] Emerging evidence from clinical and basic research suggests that lifestyle-related diseases may exacerbate CAA.

• #104 New insights into the role of lifestyle-related diseases on vascular dementia and Alzheimer’s disease

  https://www.jstage.jst.go.jp/article/vascog/5/0/5_12/_html/-char/en

  Studies using AD animal models show that diabetes mellitus and hypertension can increase the production rate of A in the brain or impair the clearance mechanism of A from the brain, both leading to A plaque formation. […] A aggregates are known to accumulate not only in the brain parenchyma but also in the cerebral blood vessels (cerebral amyloid angiopathy [CAA]). […] Recent studies also report that the vascular-damaging activity of A becomes more evident in the presence of hypertension. […] This suggests that AD-related A plays a role in the development of hypertension-induced CVD. […] CAA may be a key player linking lifestyle-related diseases, VaD, and AD. […] CAA is often accompanied by multiple cerebral microbleeds and is also known to contribute to the pathogenesis of VaD. […] Emerging evidence from clinical and basic research suggests that lifestyle-related diseases may exacerbate CAA.

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