Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia

Hypertension, Год журнала: 2023, Номер 81(1), С. 75 - 86

Опубликована: Ноя. 29, 2023

Hypertension-associated cerebral small vessel disease is a common finding in older people. Strongly associated with age and hypertension, found at autopsy over 50% of people aged ≥65 years, spectrum clinical manifestations. It the main cause lacunar stroke major source vascular contributions to cognitive impairment dementia. The brain areas affected are subcortical periventricular white matter deep gray nuclei. Neuropathological sequelae diffuse lesions (seen as hyperintensities on T2-weighted magnetic resonance imaging), ischemic foci (lacunes or microinfarcts), less commonly, microhemorrhages. most form concentric, fibrotic thickening penetrating arteries (up 300 microns outer diameter) termed arteriolosclerosis. Less forms artery atheroma lipohyalinosis (the described by C. Miller Fisher adjacent lacunes). Other microvascular that not reviewed here include amyloid angiopathy venous collagenosis. Here, we review epidemiology, neuropathology, management, genetics, preclinical models, pathogenesis hypertensive disease. Knowledge gaps initiating factors, molecular pathogenesis, relationships between arterial pathology tissue damage, possible reversibility, pharmacological targets, biomarkers. Progress anticipated from multicell transcriptomic proteomic profiling, novel experimental models further target-finding interventional studies.

Язык: Английский

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Hypertension, Neurodegeneration, and Cognitive Decline

Hypertension, Год журнала: 2024, Номер 81(5), С. 991 - 1007

Опубликована: Март 1, 2024

Elevated blood pressure is a well-established risk factor for age-related cognitive decline. Long linked to impairment on vascular bases, increasing evidence suggests potential association of hypertension with the neurodegenerative pathology underlying Alzheimer disease. Hypertension well known disrupt structural and functional integrity cerebral vasculature. However, mechanisms by which these alterations lead brain damage, enhance pathology, promote remain be established. Furthermore, critical questions concerning whether lowering antihypertensive medications prevents have not been answered. Recent developments in neurovascular biology, imaging, epidemiology, as new clinical trials, provided insights into issues. In particular, basic findings link between dysfunction pathobiology neurodegeneration shed light overlap pathology. this review, we will examine progress made relationship and, after evaluation evidence, attempt identify remaining knowledge gaps future research directions that may advance our understanding one leading health challenges time.

Язык: Английский

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Aging drives cerebrovascular network remodeling and functional changes in the mouse brain

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 30, 2024

Abstract Aging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure function in different brain areas. Here utilize mesoscale microscopy methods vivo imaging to determine detailed changes aged murine cerebrovascular networks. Whole-brain tracing shows an overall ~10% decrease length branching density ~7% increase radii brains. Light sheet 3D immunolabeling reveals increased arteriole tortuosity of Notably, vasculature pericyte densities show selective significant reductions the deep cortical layers, hippocampal network, basal forebrain We find blood extravasation, implying blood-brain barrier Moreover, awake mice demonstrates reduced baseline on-demand oxygenation despite relatively intact neurovascular coupling. Collectively, uncover regional vulnerabilities network physiological that can mediate cognitive decline aging.

Язык: Английский

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The pathobiology of neurovascular aging

Neuron, Год журнала: 2025, Номер 113(1), С. 49 - 70

Опубликована: Янв. 1, 2025

Язык: Английский

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Meningeal interleukin-17-producing T cells mediate cognitive impairment in a mouse model of salt-sensitive hypertension

Nature Neuroscience, Год журнала: 2023, Номер 27(1), С. 63 - 77

Опубликована: Дек. 4, 2023

Язык: Английский

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Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Авг. 14, 2023

Abstract Alzheimer’s disease (AD) is an aging-related form of dementia associated with the accumulation pathological aggregates amyloid beta and neurofibrillary tangles in brain. These phenomena are accompanied by exacerbated inflammation marked neuronal loss, which altogether contribute to accelerated cognitive decline. The multifactorial nature AD, allied our still limited knowledge its etiology pathophysiology, have lessened capacity develop effective treatments for AD patients. Over last few decades, genome wide association studies biomarker development, alongside mechanistic experiments involving animal models, identified different immune components that play key roles modulation brain pathology affecting progression severity. As we will relay this review, much recent efforts been directed better understanding role innate immunity, particularly microglia. However, despite lack diversity within resident cells, border tissues, especially meninges, harbour a considerable number types subtypes adaptive cells. Alongside microglia, taken centre stage as important players research, there new exciting evidence pointing namely T B cells found modulators neuroinflammation (dys)function AD. Importantly, genuine functional lymphatic vascular network present around outermost meningeal layer, dura. lymphatics directly connected peripheral system mammalian species, including humans, crucial preserving “healthy” surveillance CNS, shaping responses, not only locally at but also level tissue. In provide comprehensive view on current about vasculature, emphasizing described modulating CNS fluid macromolecule drainage, well glial function aging

Язык: Английский

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A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury

Nature Neuroscience, Год журнала: 2024, Номер 27(11), С. 2138 - 2151

Опубликована: Сен. 18, 2024

Язык: Английский

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Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood

NMR in Biomedicine, Год журнала: 2024, Номер 37(9)

Опубликована: Апрель 18, 2024

Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human imaging provided important insights into system highlighted existence interspecies differences. Current gold standard techniques for involve injection gadolinium-based contrast agents monitoring their distribution over period few hours up to 2 days. With both intrathecal intravenous injections being used, which each have own specific routes thus agent, clear understanding kinetics associated with approaches, especially differences them, is needed properly interpret results. Because known intrathecally injected agent reaches blood, albeit small concentrations, similarly some intravenously can be detected CSF, are connected will, theory, reach same compartments. However, because relative enhancement patterns, approaches will result varying sensitivities assessment different subparts system. In opinion review article, "EU Joint Programme - Neurodegenerative Disease Research (JPND)" consortium on provides an overview pharmacokinetics vivo following what typical concentrations concentration-time curves should expected. This basis optimizing interpreting contrast-enhanced MRI imaging. Furthermore, shed light how molecules may exchange brain, CSF.

Язык: Английский

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Endothelial cells and macrophages as allies in the healthy and diseased brain

Acta Neuropathologica, Год журнала: 2024, Номер 147(1)

Опубликована: Фев. 12, 2024

Abstract Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells macrophages key cellular players that mediate pathology in many CNS diseases. Macrophages brain consist CNS-associated (CAMs) [also referred to as border-associated (BAMs)] microglia, both which close neighbours even form direct contacts microvessels. Recent progress has revealed different macrophage populations a subset derived from same erythromyeloid progenitor cells. share several common features their life cycle—from invasion into early during embryonic development proliferation CNS, demise. In adults, microglia CAMs have been implicated regulating patency diameter vessels, blood flow, tightness blood–brain barrier, removal calcification, life-time Conversely, may affect polarization activation state myeloid populations. The molecular mechanisms governing pas de deux beginning be deciphered will reviewed here.

Язык: Английский

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Cardiac Contributions to Brain Health: A Scientific Statement From the American Heart Association

Stroke, Год журнала: 2024, Номер 55(12)

Опубликована: Окт. 10, 2024

The burden of neurologic diseases, including stroke and dementia, is expected to grow substantially in the coming decades. Thus, achieving optimal brain health has been identified as a public priority major challenge. Cardiovascular diseases are leading cause death disability United States around world. Emerging evidence shows that heart brain, once considered unrelated organ systems, interdependent linked through shared risk factors. More recently, studies designed unravel intricate pathogenic mechanisms underpinning this association show people with various cardiac conditions may have covert microstructural changes cognitive impairment. These findings given rise idea by addressing cardiovascular earlier life, it be possible reduce deter onset or progression impairment later life. Previous scientific statements addressed between stroke. This statement discusses link 3 prevalent adults (heart failure, atrial fibrillation, coronary disease)

Язык: Английский

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