{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:03:04Z","timestamp":1785250984851,"version":"3.55.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Nerve growth factor (NGF) is associated with neuroprotection and neural repair. However, whether NGF is associated with future stroke in humans is unknown. We determined the association between late midlife serum NGF and subsequent risk of clinical stroke, covert brain infarcts, and white matter hyperintensity volume on magnetic resonance imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">A total of 1709 stroke\u2010free participants from the FHS (Framingham Heart Study) Offspring and Omni 1 cohorts who attended Offspring examination 7\/Omni 1 examination 2, respectively (1998\u20132001), with baseline serum NGF were included. The primary outcomes were incident all\u2010cause and ischemic stroke. Secondary outcomes included covert brain infarct and white matter hyperintensity volume on magnetic resonance imaging. Serum NGF was analyzed continuously and by tertiles, adjusting for age, sex, and vascular risk factors. Cox proportional hazards regression models were used to assess the association between serum NGF and all\u2010cause and ischemic stroke risk. Linear and logistic regression models were used to evaluate the association between serum NGF levels and white matter hyperintensity volume and covert brain infarct.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Mean age was 60.6\u00b19.6\u2009years, and 47.6% were men. The median follow\u2010up for incident stroke was 19.2 (interquartile range, 14.7\u201321.3) years. The highest tertile (tertile 3) of NGF, compared with the bottom tertile (tertile 1), was associated with a reduced risk of incident all\u2010cause stroke (hazard ratio [HR], 0.59 [95% CI, 0.37\u20130.94];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.03) and ischemic stroke (HR, 0.50 [95% CI, 0.27\u20130.77];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.003). Tertile 3 versus tertile 1 of NGF was also associated with a reduced risk of covert brain infarct (odds ratio, 0.57 [95% CI, 0.34\u20130.97];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.04).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Higher serum NGF in late midlife demonstrates a protective association with future risk of silent and clinically overt stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.045426","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:56:25Z","timestamp":1776678985000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Nerve Growth Factor and Clinical Stroke and Covert Brain Infarcts: The FHS"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2042-257X","authenticated-orcid":false,"given":"Martin","family":"Mulligan","sequence":"first","affiliation":[{"name":"University of Galway","place":["Galway, Ireland"]},{"name":"The Framingham Heart Study","place":["Framingham"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-7778","authenticated-orcid":false,"given":"Alexa S.","family":"Beiser","sequence":"additional","affiliation":[{"name":"The Framingham Heart Study","place":["Framingham"]},{"name":"Boston University School of Public Health","place":["Boston"]},{"name":"Boston University Chobanian & Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saptaparni","family":"Ghosh","sequence":"additional","affiliation":[{"name":"The Framingham Heart Study","place":["Framingham"]},{"name":"Boston University Chobanian & Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6779-5106","authenticated-orcid":false,"given":"Ayantika","family":"Banerjee","sequence":"additional","affiliation":[{"name":"The Framingham Heart Study","place":["Framingham"]},{"name":"Boston University Chobanian & Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8584-1455","authenticated-orcid":false,"given":"Hugo","family":"Aparicio","sequence":"additional","affiliation":[{"name":"The Framingham Heart Study","place":["Framingham"]},{"name":"Boston University Chobanian & Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1101-2950","authenticated-orcid":false,"given":"Jose Rafael","family":"Romero","sequence":"additional","affiliation":[{"name":"The Framingham Heart Study","place":["Framingham"]},{"name":"Boston University Chobanian & Avedisian School of Medicine","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-2420","authenticated-orcid":false,"given":"Russell P.","family":"Tracy","sequence":"additional","affiliation":[{"name":"Larner College of Medicine, University of Vermont","place":["Burlington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6135-2622","authenticated-orcid":false,"given":"Sudha","family":"Seshadri","sequence":"additional","affiliation":[{"name":"The Framingham Heart Study","place":["Framingham"]},{"name":"Boston University Chobanian & Avedisian School of Medicine","place":["Boston"]},{"name":"University of Texas Health Sciences Center","place":["San Antonio"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3589-2964","authenticated-orcid":false,"given":"Emer R.","family":"McGrath","sequence":"additional","affiliation":[{"name":"University of Galway","place":["Galway, Ireland"]},{"name":"The Framingham Heart Study","place":["Framingham"]},{"name":"University of Galway","place":["Galway, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30499-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.5.654"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1217"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-239"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(03)00121-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390117"},{"key":"e_1_3_2_8_2","first-page":"3481","article-title":"Intranasal administration of nerve growth factor promotes angiogenesis via activation of PI3K\/Akt signaling following cerebral infarction in rats","volume":"10","author":"Li X","year":"2018","unstructured":"Li X, Li F, Ling L, Li C, Zhong Y. Intranasal administration of nerve growth factor promotes angiogenesis via activation of PI3K\/Akt signaling following cerebral infarction in rats. Am J Transl Res. 2018;10:3481\u20133492.","journal-title":"Am J Transl Res"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000047710"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-7435(75)90037-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv337"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.12.2201"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gheart.2012.12.007"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.000947"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040296"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.10.030"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22535"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S303833"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.06.013"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.175.4027.1251"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/35002084"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1179\/016164105X35611"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.045426","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:47:37Z","timestamp":1785250057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.045426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":21,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,5,5]]}},"alternative-id":["10.1161\/JAHA.125.045426"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.045426","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]},"assertion":[{"value":"2025-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e045426"}}