{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:44:21Z","timestamp":1792446261933,"version":"4.5.0"},"reference-count":140,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Age-related cognitive decline is increasingly recognised as arising from interacting immune and neurovascular vulnerabilities rather than from isolated insults. In this Review, we synthesise current human and mechanistic evidence within a convergence framework in which inflammaging and neurovascular unit (NVU) dysfunction are conceptualised as a feedback-coupled system. Persistent immune remodelling may promote endothelial activation, redox imbalance, pericyte\u2013astrocyte support failure, microglial priming, and impaired neurovascular coupling, thereby reducing cerebrovascular reserve and destabilising blood\u2013brain barrier (BBB) selectivity and transport. Conversely, emerging NVU dysfunction may amplify neuroimmune signalling and increase the susceptibility of white matter and synapses to late-life injury. We organise the literature around three mechanistic interfaces\u2014immune\u2013endothelium, glia\u2013vascular, and flow\u2013metabolic\u2014and assess how this framework may clarify biomarker stratification, mechanism-aligned endpoint selection, and heterogeneity of intervention responses. Current evidence is strongest for integrative plausibility across inflammatory, vascular, and cognitive domains, but remains more limited for temporal ordering, effect modification, and reversibility in humans. We highlight key uncertainties, including peripheral-to-central signalling, harmonisation of BBB metrics, and heterogeneity across mixed late-life pathologies, and assess the therapeutic implications of immune- and NVU-directed strategies.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1841958","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:33:26Z","timestamp":1783920806000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Inflammaging and neurovascular unit dysfunction in cognitive ageing: mechanisms, biomarkers, and therapeutic opportunities"],"prefix":"10.3389","volume":"18","author":[{"given":"Fan","family":"Bu","sequence":"first","affiliation":[{"name":"Department of Neurology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Qidong Hospital of Traditional Chinese Medicine","place":["Qidong, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengchi","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Henan Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Shenzhen People\u2019s Hospital (The First Affiliated Hospital Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Shenzhen People\u2019s Hospital (The First Affiliated Hospital Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shenzhen People\u2019s Hospital (The First Affiliated Hospital Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Nursing, Shenzhen People\u2019s Hospital (The First Affiliated Hospital Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Shenzhen People\u2019s Hospital (The First Affiliated Hospital Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"102257","DOI":"10.1016\/j.arr.2024.102257","article-title":"Circulating biomarkers of inflammaging and Alzheimer\u2019s disease to track age-related trajectories of dementia: can we develop a clinically relevant composite combination?","volume":"96","author":"Abbatecola","year":"2024","journal-title":"Ageing Res. 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