{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:55:21Z","timestamp":1790873721488,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Both insulin sensitivity and brain glymphatic function were linked to cognitive function in nondiabetic patients with cerebral small vessel disease (CSVD). This study aims to elucidate these complex associations through mediation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients who underwent multimodal magnetic resonance imaging (MRI) scans were recruited. Global cognitive assessment was performed by Mini\u2010Mental State Examination (MMSE), four isolated cognitive domains were assessed simultaneously. Glymphatic function was assessed using the diffusion tensor imaging along the perivascular space (DTI\u2010ALPS) index, insulin sensitivity was assessed by the homeostasis model assessment\u2013estimated insulin resistance index (HOMA\u2010IR), and HOMA\u2010IR\u22652.80 was defined as insulin resistance (IR). Mediation analysis was conducted to examine the effect of the DTI\u2010ALPS on insulin sensitivity and cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      110 CSVD patients were recruited, 40 patients were IR and 70 patients were non\u2010IR. Both the HOMA\u2010IR and DTI\u2010ALPS index were significant predictors of cognitive function, with B = \u22120.592, 95%CI, \u22120.939 to \u22120.244,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001 and B = 9.378, 95% CI, 3.376 to 15.381,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003, respectively, after adjusting for age, sex, and other confounding factors. Mediation analysis revealed that the DTI\u2010ALPS index served as a significant partial mediator in the relationship between HOMA\u2010IR and cognitive function, with direct effect = \u22120.649 (95% CI, \u22121.015 to \u22120.282,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), total effect = \u22120.743 (95% CI, \u22121.106 to \u22120.380,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), and the indirect effect = \u22120.094 (95% CI, \u22120.236 to \u22120.006,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.029), accounting for 12.66% of the total effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both the HOMA\u2010IR and the DTI\u2010ALPS index are independent risk factors for cognitive function. Furthermore, the DTI\u2010ALPS index significantly and partially mediates the relationship between the HOMA\u2010IR and cognitive function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71143","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T07:13:47Z","timestamp":1766474027000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insulin Resistance and Cognitive Function in Nondiabetic Patients With Cerebral Small Vessel Disease: Role of Brain Glymphatic Function"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiao\u2010Li","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology Shanghai Fifth People's Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Fan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology Shanghai Fifth People's Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology Renji Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Shanghai Fifth People's Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Mei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology Shanghai Fifth People's Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-836X","authenticated-orcid":false,"given":"Hu\u2010Lie","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of 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