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Leukoaraiosis or rarefied white matter (\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      ) originally described on computed tomography is one of the most prominent changes which occurs in older age. White matter hyperintensities (\n                      <jats:styled-content style=\"fixed-case\">WMH<\/jats:styled-content>\n                      ) evident on magnetic resonance imaging have become commonplace to describe\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      changes in relation to cognitive dysfunction, types of stroke injury, cerebral small vessel disease and neurodegenerative disorders including Alzheimer's disease. Substrates of\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      degeneration collectively include myelin loss, axonal abnormalities, arteriolosclerosis and parenchymal changes resulting from lacunar infarcts, microinfarcts, microbleeds and perivascular spacing.\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      cells incorporating astrocytes, oligodendrocytes, pericytes and microglia are recognized as key cellular components of the gliovascular unit. They respond to ongoing pathological processes in different ways leading to disruption of the gliovascular unit. The most robust alterations involve oligodendrocyte loss and astrocytic clasmatodendrosis with displacement of the water channel protein, aquaporin 4. These modifications likely precede arteriolosclerosis and capillary degeneration and involve tissue oedema, breach of the blood\u2013brain barrier and induction of a chronic hypoxic state in the deep\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      . Several pathophysiological mechanisms are proposed to explain how\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      changes commencing with haemodynamic changes within the vascular system impact on cognitive dysfunction. Animal models simulating cerebral hypoperfusion in man have paved the way for several translational opportunities. Various compounds with variable efficacies have been tested to reduce oxidative stress, inflammation and blood\u2013brain barrier damage in the\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      . Our review demonstrates that\n                      <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>\n                      degeneration encompasses multiple substrates and therefore more than one pharmacological approach is necessary to preserve axonal function and prevent cognitive impairment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14271-fig-0005-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/journal\/10.1111\/(ISSN)1471-4159\/homepage\/special_issues.htm#Vascular Dementia\">This article is part of the Special Issue \u201cVascular Dementia\u201d<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.14271","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T01:32:41Z","timestamp":1512523961000},"page":"617-633","source":"Crossref","is-referenced-by-count":198,"title":["White matter degeneration in vascular and other ageing\u2010related dementias"],"prefix":"10.1111","volume":"144","author":[{"given":"Yoshiki","family":"Hase","sequence":"first","affiliation":[{"name":"Neurovascular Research Group Institute of Neuroscience Newcastle University Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9620-3691","authenticated-orcid":false,"given":"Karen","family":"Horsburgh","sequence":"additional","affiliation":[{"name":"Centre for Neuroregeneration University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Neurology National Cerebral and Cardiovascular Center Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7907-4923","authenticated-orcid":false,"given":"Raj N.","family":"Kalaria","sequence":"additional","affiliation":[{"name":"Neurovascular Research Group Institute of Neuroscience Newcastle University Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2012.01308.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.679936"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.006849"},{"key":"e_1_2_10_6_1","first-page":"280","volume-title":"Institute of Neuroscience","author":"Akinyemi R. 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