{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:30:39Z","timestamp":1786649439058,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the co-occurrence patterns of inflammatory, carotid atherosclerotic, MRI-based brain atrophy-related, and cognitive alterations in patients with Chronic Insomnia Disorder (CID), with a focus on exploring the statistical association of IL-6 with insomnia severity and cognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 88 patients with chronic insomnia and 60 healthy controls undergoing physical examinations were recruited from Chaohu Hospital of Anhui Medical University between May 2024 and April 2025. Insomnia severity was assessed using the Athens Insomnia Scale (AIS). Serum levels of white blood cell count (WBC), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and lipid profiles were measured using automated hematology and biochemistry analyzers. Carotid intima-media thickness (CIMT) and plaque incidence were evaluated via color Doppler ultrasound. Brain morphological changes were examined using magnetic resonance imaging (MRI), and global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Differences in indicators between the two groups were compared. Pearson correlation analysis was used to examine the relationships among hs-CRP, IL-6, lipid levels, cognitive decline, and insomnia severity. Subsequently, Model 4 of the SPSS macro PROCESS (v4.1) was used as an exploratory cross-sectional path model. Because the exposure, mediator, and outcome were measured at the same time point, the model was interpreted as an association-based indirect-effect analysis rather than evidence of causal mediation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      (1) Compared to the control group, the chronic insomnia group had significantly higher levels of hs-CRP, IL-6, homocysteine, and triglycerides, and significantly lower levels of high-density lipoprotein (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). (2) Both CIMT and carotid plaque incidence were higher in the chronic insomnia group than in the control group (L-CIMT: 0.89 \u00b1 0.22 vs. 0.74 \u00b1 0.17; R-CIMT: 0.90 \u00b1 0.24 vs. 0.76 \u00b1 0.15; plaque incidence: 29.0% vs. 15.0%). (3) The frontal lobe b\/i ratio was slightly higher in the chronic insomnia group, but the difference was not statistically significant. Significant differences were found between the two groups in the cerebellar a\/h ratio, temporal lobe e\/k ratio, average hippocampal width, average sulcal width, and MMSE scores (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). (4) Pearson analysis showed that in the chronic insomnia group, IL-6 and triglyceride levels were positively correlated with AIS scores (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05) and negatively correlated with MMSE scores (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). (5) The exploratory path model indicated a significant positive association between triglyceride (TG) levels and AIS scores (R = 0.36,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). TG levels showed a negative but non-significant predictive effect on MMSE scores (B = \u22120.96,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05). Testing IL-6 in the AIS-MMSE path framework revealed a significant positive association with AIS scores (R = 0.30,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05), and IL-6 was significantly associated with MMSE scores in the regression model (B = \u22120.16,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Further indirect-effect analysis showed a direct effect of \u22120.1534 (accounting for 74.63% of the total effect) and an indirect effect of \u22120.0528 (accounting for 25.37% of the total effect), with a total effect of \u22120.2052. These results should be interpreted cautiously because of the cross-sectional design. (6) Patients with CID simultaneously exhibited elevated inflammatory levels, carotid atherosclerosis, MRI-based brain atrophy-related changes, and lower cognitive screening scores. This pattern suggests that CID is associated with multi-system clinical and biological alterations. IL-6 was statistically involved in the AIS-MMSE association in an exploratory cross-sectional path model. Because aging is a complex process involving multiple biological pathways beyond inflammaging, vascular aging, brain atrophy, and cognition, these findings should be interpreted as evidence of associated biomarker patterns rather than proof that CID globally accelerates biological aging or directly causes neurodegeneration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1868267","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:54:05Z","timestamp":1786647245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic insomnia is associated with inflammatory, carotid atherosclerotic, MRI-based brain atrophy-related, and cognitive alterations: the potential role of IL-6"],"prefix":"10.3389","volume":"13","author":[{"given":"Han","family":"Li","sequence":"first","affiliation":[{"name":"Department of General Practice, The Fourth Affiliated Hospital of Anhui Medical University (Chaohu Hospital of Anhui Medical University)","place":["Chaohu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of General Practice, The Fourth Affiliated Hospital of Anhui Medical University (Chaohu Hospital of Anhui Medical University)","place":["Chaohu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of General Practice, The Fourth Affiliated Hospital of Anhui Medical University (Chaohu Hospital of Anhui Medical University)","place":["Chaohu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdan","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of General Practice, The Fourth Affiliated Hospital of Anhui Medical University (Chaohu Hospital of Anhui Medical University)","place":["Chaohu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of General Practice, The Fourth Affiliated Hospital of Anhui Medical University (Chaohu Hospital of Anhui Medical University)","place":["Chaohu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengfeng","family":"Su","sequence":"additional","affiliation":[{"name":"Department of General Practice, The Fourth Affiliated Hospital of Anhui Medical University (Chaohu Hospital of Anhui Medical University)","place":["Chaohu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1043262","DOI":"10.3389\/fnins.2022.1043262","article-title":"Fatigue performance in patients with chronic insomnia","volume":"16","author":"Xu","year":"2022","journal-title":"Front Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1152\/physrev.00010.2018","article-title":"The sleep-immune crosstalk in health and disease","volume":"99","author":"Besedovsky","year":"2019","journal-title":"Physiol Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1080\/23328940.2022.2109932","article-title":"Sleep disruption induces activation of inflammation and heightens risk for infection disease: role of impairments in thermoregulation and elevated ambient temperature","volume":"10","author":"Irwin","year":"2022","journal-title":"Temperature."},{"key":"B4","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat Rev Endocrinol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1016\/j.jacc.2009.09.009","article-title":"Leducq Transatlantic Network on Atherothrombosis. 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