{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:24:23Z","timestamp":1792589063228,"version":"4.5.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose\u2014<\/jats:title>\n                    <jats:p>Inflammation is involved in the pathogenesis of large artery atherosclerosis, ischemic stroke, and Alzheimer dementia. However, the role of inflammation in cerebral small vessel disease and neurodegeneration remains poorly understood. We hypothesize that CRP (C-reactive protein) is associated with brain structural changes and may interact with amyloid to produce vascular and degenerative damage. We examined the association of CRP levels with imaging markers of cerebral small vessel disease and neurodegeneration. Furthermore, we studied the association of CRP with plasma A\u03b2 (amyloid-\u03b2) levels and their joint effects with imaging markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\u2014<\/jats:title>\n                    <jats:p>We included 2814 persons (mean age, 56.9 years; 44.8% women) from the Rotterdam Study with complete data on CRP and 1.5 T brain magnetic resonance imaging scans. A\u03b2 levels were measured in a subsample (n=736). Markers of cerebral small vessel disease included lacunes, white matter hyperintensities, microbleeds, and enlarged perivascular spaces. Neurodegeneration was assessed by smaller volumes of gray matter, white matter, and hippocampus. Plasma levels of A\u03b21\u201338, A\u03b21\u201340, and A\u03b21\u201342 were assessed using ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results\u2014<\/jats:title>\n                    <jats:p>\n                      Higher CRP levels were associated with larger white matter hyperintensities volume (\u03b2=0.07; 95% CI, 0.00\u20130.13), increasing lacunar (rate ratios, 1.61; 95% CI, 1.19\u20132.19), enlarged perivascular spaces (rate ratios, 1.01; 95% CI, 1.00\u20131.03), and deep\/infratentorial microbleeds (rate ratios, 1.30; 95% CI, 1.00\u20131.69) counts. People with high CRP levels had small gray matter volume. We also found significant interaction between CRP and A\u03b2 such that among persons in higher tertiles of A\u03b21\u201342, a strong association was observed between CRP and lacunar (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction, 0.004), enlarged perivascular spaces (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction, 0.002), and microbleed counts (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction, &lt;0.001). Similarly, among persons in higher tertile of A\u03b21\u201338, a strong association was observed between CRP and microbleed counts (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction, 0.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Higher CRP levels were associated with subclinical markers of cerebral small vessel disease and neurodegeneration. This effect was augmented by an interaction between CRP and A\u03b2 levels. Future longitudinal studies focusing on joint effects of CRP and A\u03b2 on progression of magnetic resonance imaging markers and cognitive decline are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.118.022317","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T05:14:56Z","timestamp":1539580496000},"page":"2692-2698","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["C-Reactive Protein, Plasma Amyloid-\u03b2 Levels, and Their Interaction With Magnetic Resonance Imaging Markers"],"prefix":"10.1161","volume":"49","author":[{"given":"Saima","family":"Hilal","sequence":"first","affiliation":[{"name":"From the Departments of Radiology and Nuclear Medicine (S.H., M.A.I., M.W.V.), Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Epidemiology (S.H., M.A.I., O.H.F.), Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"From the Departments of Radiology and Nuclear Medicine (S.H., M.A.I., M.W.V.), Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Epidemiology (S.H., M.A.I., O.H.F.), Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel M.","family":"Verbeek","sequence":"additional","affiliation":[{"name":"From the Departments of Radiology and Nuclear Medicine (S.H., M.A.I., M.W.V.), Erasmus Medical Center, Rotterdam, the Netherlands"},{"name":"Department of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands (M.M.V.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar H.","family":"Franco","sequence":"additional","affiliation":[{"name":"Epidemiology (S.H., M.A.I., O.H.F.), Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stoops","sequence":"additional","affiliation":[{"name":"ADx NeuroSciences, Gent, Belgium (E.S., H.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Vanderstichele","sequence":"additional","affiliation":[{"name":"ADx NeuroSciences, Gent, Belgium (E.S., H.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiro J.","family":"Niessen","sequence":"additional","affiliation":[{"name":"Medical Informatics (W.J.N.), Erasmus Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike W.","family":"Vernooij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901143400207"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2004.04.028"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003233421202"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141506"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/43.1.52"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000222780"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000343302"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-4949.2011.00725.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70104-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.06.053"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.506337"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018675"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.621193"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000248768.40043.f9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.01.014"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02970-X"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2007-12204"},{"key":"e_1_3_3_19_2","first-page":"53","article-title":"Alzheimer disease and neuroinflammation.","volume":"59","author":"McGeer PL","year":"2000","unstructured":"McGeer, PL, McGeer, EG, Yasojima, K. Alzheimer disease and neuroinflammation. J Neural Transm Suppl. 2000;59:53\u201357.","journal-title":"J Neural Transm Suppl"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2009.01.001"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2011.12.007"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170458"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-131373"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0377-5"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-018-0395-6"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv021"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-015-0105-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.000620"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.05.018"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00569-X"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.03.012"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1177\/1741826711414623"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.10.030"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.3.652"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg040"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000125527.41598.68"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001279"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-5-12"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22073"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1177\/0891988708328216"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2009.01.017"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2005.07.003"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088417"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0750634.x"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.178962"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhi044"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.118.022317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T13:34:00Z","timestamp":1762954440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.118.022317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1161\/STROKEAHA.118.022317"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.118.022317","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"2018-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-19","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}