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Aging, hypertension, and diabetes are the primary risk factors for Alzheimer\u2019s disease and Alzheimer\u2019s disease and related dementias (AD\/ADRD). There are no effective treatments for AD\/ADRD to date. An emerging body of evidence indicates that cerebral vascular dysfunction and hypoperfusion precedes the development of other AD pathological phenotypes and cognitive impairment. However, vascular contribution to dementia is not currently well understood. This commentary highlights the emerging concepts and mechanisms underlying the microvascular contribution to AD\/ADRD, including hypotheses targeting the anterograde and retrograde cerebral vascular pathways, as well as the cerebral capillaries and the venous system. We also briefly discuss vascular endothelial dysfunction, oxidative stress, inflammation, and cellular senescence that may contribute to impaired cerebral blood flow autoregulation, neurovascular uncoupling, and dysfunction of cerebral capillaries and the venous system.<\/jats:p>","DOI":"10.1556\/2060.2022.00020","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T15:46:11Z","timestamp":1648050371000},"page":"20-30","update-policy":"https:\/\/doi.org\/10.1556\/policypage.crossmark.crossref.1","source":"Crossref","is-referenced-by-count":23,"title":["Contribution of cerebral microvascular mechanisms to age-related cognitive impairment and dementia"],"prefix":"10.1556","volume":"109","author":[{"given":"Xing","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reece F.","family":"Crumpler","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirby N.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jena\u2019 N.","family":"Mazique","sequence":"additional","affiliation":[{"name":"Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-3610","authenticated-orcid":true,"given":"Fan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA"},{"name":"Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"425","reference":[{"issue":"3","key":"ref0","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/alz.12328","article-title":"Alzheimer's disease facts and figures","volume":"17","author":"1","year":"2021","unstructured":"1. 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