{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:31:30Z","timestamp":1786379490030,"version":"build-2736575974"},"reference-count":51,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82571751, 81971181, 12231018, 82401397"],"award-info":[{"award-number":["82571751, 81971181, 12231018, 82401397"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Jiao Tong University Medical Engineering Cross Research Funds","award":["YG2024ZD27"],"award-info":[{"award-number":["YG2024ZD27"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In cerebral small vessel disease (CSVD), the burden of white matter hyperintensities (WMH) does not fully account for cognitive impairment, suggesting the involvement of intermediary mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We investigated whether a gray matter atrophy network acts as the key mediator linking topologically specific (deep) WMH to multidomain cognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective study, 260 patients with CSVD (62 cognitively normal, 125 with mild impairment, 73 with dementia) were included. Cognitive status was assessed neuropsychologically. 3.0\u2005T MRI identified an atrophy network. We then conducted pre-specified mediation analyses and a primary confirmatory analysis using structural equation modeling (SEM) to test whether this atrophy network mediated the effect of deep WMH on cognitive performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A 41-region atrophy network was identified\n                      <jats:bold>,<\/jats:bold>\n                      primarily involving the medial temporal lobe and thalamus, that was significantly associated with cognitive status. The final SEM demonstrated excellent fit, showing that higher deep WMH burden was associated with greater network atrophy (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      \u2009=\u20090.145, p\u2009&lt;\u20090.05), which in turn was strongly associated with poorer executive function (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.64, p\u2009&lt;\u20090.001) and memory (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.572, p\u2009&lt;\u20090.001). The direct effect of WMH on cognition was not statistically significant in the model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that in CSVD, a unified network of gray matter atrophy acts as a powerful statistical mediator in the effect of deep white matter injury on cognitive decline. This atrophy pattern may represent a more direct biomarker of the neurodegenerative process underlying cognitive impairment than WMH burden alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261457126","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:55:39Z","timestamp":1781772939000},"page":"1182-1193","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deep white matter injury and cognitive decline in cerebral small vessel disease: Mediation by a unified atrophy network"],"prefix":"10.1177","volume":"112","author":[{"given":"Chengzhe","family":"Wang","sequence":"first","affiliation":[{"name":"Tongren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine"},{"name":"Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of 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