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血管因素对衰老和痴呆中认知功能减退的影响。

The vascular contribution to cognitive decline in ageing and dementia.

作者信息

Anderle Silvia, Dixon Michael, Quintela-Lopez Tania, Sideris-Lampretsas George, Attwell David

机构信息

BHF/UK-DRI Centre for Vascular Dementia Research, University College London, London, UK.

Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

出版信息

Nat Rev Neurosci. 2025 Aug 4. doi: 10.1038/s41583-025-00950-1.


DOI:10.1038/s41583-025-00950-1
PMID:40760183
Abstract

There is increasing evidence to suggest that vascular dysfunction can contribute to cognitive decline in ageing and dementia. This dysfunction can take the form of a reduction of cerebral blood flow (CBF), a loss of blood-brain barrier (BBB) function or a combination of the two. Indeed, CBF and BBB changes may be causally linked, although this possible causality and its directionality are understudied. Appreciation of the role of vascular dysfunction in initiating cognitive decline in ageing and dementia, as well as the mechanisms involved, is important because it opens up new avenues for the development of much-needed therapies for these conditions, which are becoming major causes of death. Here we assess the evidence for the importance of vascular contributions to dementia, draw parallels with changes that occur in normal ageing and discuss the initiating cells and signalling mechanisms involved. We suggest that attempting to maintain or restore CBF should be a central aim of therapeutic strategies.

摘要

越来越多的证据表明,血管功能障碍可能导致衰老和痴呆过程中的认知衰退。这种功能障碍可以表现为脑血流量(CBF)减少、血脑屏障(BBB)功能丧失或两者兼而有之。事实上,CBF和BBB的变化可能存在因果联系,尽管这种可能的因果关系及其方向性尚未得到充分研究。认识到血管功能障碍在引发衰老和痴呆中的认知衰退的作用以及其中涉及的机制很重要,因为这为开发针对这些日益成为主要死因的疾病的急需疗法开辟了新途径。在这里,我们评估血管因素对痴呆重要性的证据,将其与正常衰老过程中发生的变化进行比较,并讨论涉及的起始细胞和信号传导机制。我们认为,试图维持或恢复CBF应该是治疗策略的核心目标。

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本文引用的文献

[1]
Interleukin-34-dependent perivascular macrophages promote vascular function in the brain.

Immunity. 2025-5-13

[2]
Endothelial cells as key players in cerebral small vessel disease.

Nat Rev Neurosci. 2025-3

[3]
Longitudinal changes in white matter free water in cerebral small vessel disease: Relationship to cerebral blood flow and white matter fiber alterations.

J Cereb Blood Flow Metab. 2025-5

[4]
Neuroinflammation in Alzheimer disease.

Nat Rev Immunol. 2025-5

[5]
Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow.

Nat Commun. 2024-10-7

[6]
Inhibiting Ca channels in Alzheimer's disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia.

Nat Neurosci. 2024-11

[7]
A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.

Nat Neurosci. 2024-11

[8]
Predicting white-matter hyperintensity progression and cognitive decline in patients with cerebral small-vessel disease: a magnetic resonance-based habitat analysis.

Quant Imaging Med Surg. 2024-9-1

[9]
Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer's disease model mice.

Nat Neurosci. 2024-9

[10]
Aging drives cerebrovascular network remodeling and functional changes in the mouse brain.

Nat Commun. 2024-7-30

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