{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:27:40Z","timestamp":1794029260767,"version":"4.8.0"},"reference-count":56,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["PTC-18-543823"],"award-info":[{"award-number":["PTC-18-543823"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP201803PJ8"],"award-info":[{"award-number":["MOP201803PJ8"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vascular mild cognitive impairment (vaMCI) is frequently accompanied by neuropsychiatric symptoms (NPS), particularly apathy, which are associated with white matter hyperintensities (WMH). N-acetylcysteine (NAC) combined with exercise may provide neuroprotective benefits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We hypothesized that baseline frontal and global WMH burden would moderate the neuropsychiatric response to NAC plus exercise. We further hypothesized that the strongest domain-specific effects would be observed for apathy and affective dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants with vaMCI were randomized to NAC (2400\u2005mg daily) or placebo plus exercise for 6 months. WMH volumes were quantified using structural MRI. NPS were assessed using the Mild Behavioral Impairment Checklist (MBI-C) at baseline, 3 months, and 6 months. Negative binomial generalized linear mixed models examined WMH\u2009\u00d7\u2009time\u2009\u00d7\u2009treatment interactions. False discovery rate (FDR) correction was applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-one participants were included. Lower baseline frontal (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      \u2009=\u20090.229, SE\u2009=\u20090.070, FDR-adjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.007) and global (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      \u2009=\u20090.258, SE\u2009=\u20090.080, FDR-adjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.007) WMH volume was associated with greater reductions in NPS over 6 months in the NAC plus exercise group. This effect was driven by improvements in apathy (frontal:\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      \u2009=\u20090.186, SE\u2009=\u20090.076, FDR-adjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.048; global:\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      \u2009=\u20090.207, SE\u2009=\u20090.089, FDR-adjusted\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.049).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Baseline WMH burden moderates neuropsychiatric treatment response in vaMCI. These findings support the importance of optimizing care for cerebrovascular risk factors in this vulnerable population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261490542","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:46:01Z","timestamp":1791391561000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["White matter hyperintensities moderate neuropsychiatric response to N-acetylcysteine and exercise therapy in vascular mild cognitive impairment"],"prefix":"10.1177","author":[{"given":"Ethan","family":"Mah","sequence":"first","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejin","family":"Kang","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"Sunnybrook Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto Scarborough"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5529-3731","authenticated-orcid":false,"given":"Zahinoor","family":"Ismail","sequence":"additional","affiliation":[{"name":"University of Calgary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"Black","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto Scarborough"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingshan","family":"Cao","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9277-6110","authenticated-orcid":false,"given":"Nathan","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Marzolini","sequence":"additional","affiliation":[{"name":"University Health Network"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Oh","sequence":"additional","affiliation":[{"name":"University Health Network"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghan Jenny","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Survilla","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Swardfager","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Vieira","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-1975","authenticated-orcid":false,"given":"Mark J.","family":"Rapoport","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-6637","authenticated-orcid":false,"given":"Krista L.","family":"Lanct\u00f4t","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute"},{"name":"University of Toronto"},{"name":"University of Toronto"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03325158"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1590\/1980-57642015dn93000004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2022.12.203"},{"key":"e_1_3_3_6_2","article-title":"Apathy as a determinant of health behaviors in older adults: implications for dementia risk reduction","volume":"15","author":"Harrison F","year":"2023","unstructured":"Harrison F, Mortby ME, Mather KA, et al. 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