Anderle Silvia, Dixon Michael, Quintela-Lopez Tania, Sideris-Lampretsas George, Attwell David
BHF/UK-DRI Centre for Vascular Dementia Research, University College London, London, UK.
Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Nat Rev Neurosci. 2025 Aug 4. doi: 10.1038/s41583-025-00950-1.
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.
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。
Nat Rev Neurosci. 2025-8-4
Cochrane Database Syst Rev. 2021-11-8
Cochrane Database Syst Rev. 2022-7-14
Psychopharmacol Bull. 2024-7-8
Health Technol Assess. 2024-10
Cochrane Database Syst Rev. 2021-2-22
Cochrane Database Syst Rev. 2003
Cochrane Database Syst Rev. 2016-11-1
Nat Rev Neurosci. 2025-3
Nat Rev Immunol. 2025-5
Nat Commun. 2024-10-7