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Few studies have evaluated the relationship between circulating RAS components and incident cognitive decline or impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our study aims to evaluate the relationship between circulating RAS biomarkers (angiotensin II [ANGII], angiotensin 1-7 [ANG1-7], angiotensin converting enzyme-1 [ACE-1], and 2 [ACE-2]), in initially cognitively healthy adults, and incident cognitive decline and cognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this secondary analysis, 310 community-dwelling participants from the randomized controlled Action for Health in Diabetes (Look AHEAD) study without dementia, who were not on RAS-altering medication, were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Participants, compared to those excluded, were more likely to be female (65%), white (76%), overweight (34%), have lower baseline HbA1c (6.7%), lower SBP (119.7 mmHg), lower serum creatinine (0.79\u2005mg\/dL), higher total cholesterol (190.1\u2005mg\/dL) and LDL (112.5\u2005mg\/dL), and higher history of dyslipidemia (65%) at baseline. 1 SD increase of ANG1-7 measured in year 1 was associated with lower odds of cognitive impairment (OR = 0.35, 95% CI 0.16-0.77; p\u2009=\u20090.001), while higher ANG1-7 levels predicted better global cognitive function [\u03b2 x 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      \u2009=\u20091.03 (0.50); p\u2009=\u20090.039], 15 years later.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results provide preliminary evidence that circulating RAS components are predictive of protection against cognitive impairment and decline and may serve as a marker of the early stages of dementia. Further research is warranted to fully understand the relationship between the brain and the circulatory RAS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261458824","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:56:54Z","timestamp":1781773014000},"page":"1497-1508","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between renin angiotensin system and cognitive outcomes over 15 years: The Look AHEAD study"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-6534","authenticated-orcid":false,"given":"Sevil","family":"Yasar","sequence":"first","affiliation":[{"name":"Johns Hopkins University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-9166","authenticated-orcid":false,"given":"Andrea","family":"Anderson","sequence":"additional","affiliation":[{"name":"Wake Forest University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-3513","authenticated-orcid":false,"given":"Kathleen M.","family":"Hayden","sequence":"additional","affiliation":[{"name":"Wake Forest University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-0047","authenticated-orcid":false,"given":"Owen T.","family":"Carmichael","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1194-0092","authenticated-orcid":false,"given":"Jeanne M.","family":"Clark","sequence":"additional","affiliation":[{"name":"Rutgers Robert Wood Johnson Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-7421","authenticated-orcid":false,"given":"Michelle C.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Johns Hopkins University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-8347","authenticated-orcid":false,"given":"Daniel J.","family":"Asby","sequence":"additional","affiliation":[{"name":"University of Bristol"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7542-1139","authenticated-orcid":false,"given":"Patrick G.","family":"Kehoe","sequence":"additional","affiliation":[{"name":"University of Bristol"},{"name":"University of Bristol"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8594-1640","authenticated-orcid":false,"given":"Scott","family":"Miners","sequence":"additional","affiliation":[{"name":"University of Bristol"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3711-1949","authenticated-orcid":false,"given":"Mark A.","family":"Espeland","sequence":"additional","affiliation":[{"name":"Wake Forest University"},{"name":"Wake Forest University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2013.812631"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161265"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2009-1002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101612"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170944"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.07.006"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0217-7"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-006-0190-8"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.09.012"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190721"},{"key":"e_1_3_3_13_2","first-page":"163","article-title":"Angiotensin-converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes","volume":"18","author":"Miners S","year":"2009","unstructured":"Miners S, Ashby E, Baig S, et al. 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