{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:31:33Z","timestamp":1785429093485,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-15-00183-P"],"award-info":[{"award-number":["22-15-00183-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22-15-00183-P"],"award-info":[{"award-number":["22-15-00183-P"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>A key mechanism in the pathogenesis of cerebral small vessel disease (CSVD) is endothelial dysfunction associated with impaired metabolism of nitric oxide (NO) and its main substrate, L-arginine. The aim of the study was to assess parameters of L-arginine metabolism and their association with MRI-defined brain damage in CSVD patients. A total of 100 CSVD patients (according to MRI STRIVE standards) and cognitive impairment (CI) of varying severity, as well as 20 healthy volunteers, were analyzed. Levels of L-arginine and its metabolites\u2014L-ornithine, L-citrulline, and asymmetric dimethylarginine (ADMA)\u2014were measured; diffusion tensor MRI, MRI volumetry, and morphometry were performed. A threshold level of L-arginine (51.25 \u03bcmol\/L) was identified, above which an association with CI was observed. Patients with L-arginine \u2265 51.25 \u03bcmol\/L demonstrated poorer performance on cognitive tests (Stroop test, trail-making test (TMT)-B, TMT B\u2013A, 10-word test) and more severe brain damage, reflected by greater severity of MRI markers (white matter hyperintensities, microbleeds), changes in brain component volumes, cortical atrophy in specific regions, and impairment of white matter microstructural integrity. The obtained data indicate a pathogenetic link between disturbances in L-arginine homeostasis and the development of CSVD with CI and support the need for further studies aimed at refining approaches to their correction.<\/jats:p>","DOI":"10.3390\/biom16060914","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["L-Arginine and Its Metabolites in Age-Related Cerebral Small Vessel Disease with Cognitive Impairment"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9929-2725","authenticated-orcid":false,"given":"Larisa","family":"Dobrynina","sequence":"first","affiliation":[{"name":"Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Byrochkina","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Shamtieva","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-6063","authenticated-orcid":false,"given":"Elena","family":"Kremneva","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2523-333X","authenticated-orcid":false,"given":"Maryam","family":"Zabitova","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla","family":"Shabalina","sequence":"additional","affiliation":[{"name":"Russian Center of Neurology and Neurosciences, 125367 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1037\/a0022348","article-title":"Neurocognitive functions and everyday functions change together in old age","volume":"25","year":"2011","journal-title":"Neuropsychology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1161\/01.STR.0000058480.77236.B3","article-title":"Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia","volume":"34","author":"Wardlaw","year":"2003","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1111\/j.1365-2990.2011.01170.x","article-title":"Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: A blinded, controlled immunohistochemical study of 5-to 21-week-old rats","volume":"37","author":"Bailey","year":"2011","journal-title":"Neuropathol. 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