{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:23:59Z","timestamp":1787185439143,"version":"build-2736575974"},"reference-count":50,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008358","name":"Hersenstichting","doi-asserted-by":"publisher","award":["DR-2019-003"],"award-info":[{"award-number":["DR-2019-003"]}],"id":[{"id":"10.13039\/501100008358","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Effective pharmacological treatments for Post-Stroke Cognitive Impairment (PSCI) remain elusive. Preclinical studies have shown that phosphodiesterase 4 (PDE4) inhibition improved cognition, particularly memory, in post-stroke animal models and in healthy young and elderly individuals. This study tested whether the PDE4 inhibitor roflumilast could improve memory in PSCI patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A double-blind randomized placebo-controlled trial (RCT) included 100 community-dwelling participants receiving roflumilast (100\u2009\u00b5g q.d.) or placebo (\n                      <jats:bold>\n                        <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      <\/jats:bold>\n                      \u2009=\u200950 per group). Participants were 41\u201370\u2009years and had suffered a cerebrovascular accident more than a year ago. They had subjective memory complaints and scored below the normative score on the delayed recall of the verbal learning test (VLT). After the RCT, 42 placebo group participants completed a 3-month open label extension (OLE). The primary outcome was the VLT delayed recall score. Roflumilast efficacy in the RCT was estimated through analysis of covariance (ANCOVA) with (post hoc) and without adjustment for baseline prognostic covariates defined a priori. In the OLE, general linear model repeated measures analyses were used. Secondary outcomes related to cognition, mood, and daily functioning.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Of the 97 participants completing the study (roflumilast: 48; placebo: 49), primary ANCOVA indicated a larger response in the roflumilast group on VLT and Rivermead Behavioural Memory Test (stories) at endpoint with non-significant moderate effect sizes (Cohen\u2019s\n                      <jats:bold>\n                        <jats:italic toggle=\"yes\">d<\/jats:italic>\n                      <\/jats:bold>\n                      : 0.31\u20130.36). When post hoc adjusting for prognostic baseline covariates, effect sizes (0.33\u20130.40) became significant. Adverse events were similar in both groups. In the OLE, all memory test scores improved with medium to large significant effect sizes (Partial \u03b7\n                      <jats:sup>2<\/jats:sup>\n                      : 0.079\u20130.171).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Roflumilast appeared to improve memory and was not associated with adverse effects. Results support further clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811261436581","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T04:29:17Z","timestamp":1777091357000},"page":"1415-1429","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The effects of the PDE4 inhibitor roflumilast on cognitive performance after a cerebrovascular accident: a double-blind randomized placebo-controlled trial with an open label extension (ROSTMEMA)"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-0632","authenticated-orcid":false,"given":"Jill","family":"Kerckhoffs","sequence":"first","affiliation":[{"name":"Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, the Netherlands"},{"name":"Limburg Brain Injury Centre, Maastricht University, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ieke","family":"Winkens","sequence":"additional","affiliation":[{"name":"Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, the Netherlands"},{"name":"Limburg Brain Injury Centre, Maastricht University, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-9517","authenticated-orcid":false,"given":"Arthur","family":"Ooghe","sequence":"additional","affiliation":[{"name":"Cognivia, Mont-Saint-Guibert, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2405-0753","authenticated-orcid":false,"given":"Samuel","family":"Branders","sequence":"additional","affiliation":[{"name":"Cognivia, Mont-Saint-Guibert, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos","family":"Prickaerts","sequence":"additional","affiliation":[{"name":"Peitho Translational, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4337-7479","authenticated-orcid":false,"given":"Arjan","family":"Blokland","sequence":"additional","affiliation":[{"name":"Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01321-w"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3999(01)00296-3"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2019.10.006"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.01.014"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.106"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.05.032"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/09622802211065246"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/sja.SJA_559_18"},{"key":"e_1_3_3_10_1","unstructured":"EMA EG (2015) Guideline on adjustment for baseline covariates in clinical trials (p. 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