Telomere and mitochondria mediated the association between dietary inflammatory index and mild cognitive impairment: A prospective cohort study Author: Qian Liu#1,2, Zhenshu Li#1,2, Ling Huang#1,2, Dezheng Zhou1,2, Jingzhu Fu1,2, Huilian Duan1,2, Zehao Wang1,2, Tong Yang1,2, Jing Zhao1,2, Wen Li1,2, Huan Liu1,2, Fei Ma2,3, Changqing Sun4, Guangshun Wang5, Yue Du2,6, Meilin Zhang1,2, Yongjie Chen7,8, Guowei Huang9,10 Affiliation: <sup>1</sup> Department of Nutrition &amp; Food Science, School of Public Health, Tianjin Medical University, Tianjin, China. <sup>2</sup> Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China. <sup>3</sup> Department of Epidemiology &amp; Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China. <sup>4</sup> Neurosurgical Department of Baodi Clinical College, Tianjin Medical University, Tianjin, China. <sup>5</sup> Department of Tumor, Baodi Clinical College of Tianjin Medical University, Tianjin, China. <sup>6</sup> Department of Social Medicine and Health Management, School of Public Health, Tianjin Medical University, Tianjin, China. <sup>7</sup> Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China. chenyongjie@tmu.edu.cn. <sup>8</sup> Department of Epidemiology &amp; Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China. chenyongjie@tmu.edu.cn. <sup>9</sup> Department of Nutrition &amp; Food Science, School of Public Health, Tianjin Medical University, Tianjin, China. huangguowei@tmu.edu.cn. <sup>10</sup> Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China. huangguowei@tmu.edu.cn. Conference/Journal: Immun Ageing Date published: 2023 Jan 5 Other: Volume ID: 20 , Issue ID: 1 , Pages: 1 , Special Notes: doi: 10.1186/s12979-022-00326-4. , Word Count: 286 Background: Diet and chronic inflammation might play a major role in the pathogenesis of mild cognitive impairment (MCI). In addition, peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) might mediate the relationship between inflammation and MCI risk. The purpose of the present study is to evaluate whether inflammatory potential of diet assessed by dietary inflammatory index (DII), chronic inflammation, peripheral blood LTL, and mtDNAcn were associated with the risk of MCI. Results: A population-based cohort study was conducted with a total of 2944 participants. During a median follow-up of 2 years, 438 (14.90%) individuals were new-onset MCI. After adjustment, a higher score of DII (hazard ratio [HR]: 1.056, 95% CI: 1.005, 1.109), a higher log systemic immune inflammation index (SII) (HR: 1.333, 95% CI: 1.089, 1.633) and log system inflammation response index (SIRI) (HR: 1.487, 95% CI: 1.024, 2.161) predicted elevated risk of MCI. An increased mtDNAcn (HR: 0.843, 95% CI: 0.712, 0.997), but not LTL, predicted a decreased risk of MCI. Negative associations of log SII with LTL (β:-0.359, 95% CI: -0.445, -0.273) and mtDNAcn (β:-0.048, 95% CI: -0.090, -0.006) were found. Additionally, negative associations of log SIRI with LTL (β: -0.035, 95% CI: -0.052, -0.017) and mtDNAcn (β:-0.136, 95% CI: -0.216, -0.056) were also found. Path analysis suggested that SIRI, LTL, and mtDNAcn, in series, have mediation roles in the association between DII score and MCI risk. Conclusions: Higher DII, SII, and SIRI might predict a greater risk of MCI, while a longer LTL and an increased mtDNAcn were linked to a reduced risk of MCI among the older population. LTL and mtDNAcn could play mediation roles in the association between DII and MCI risk. Keywords: Dietary inflammatory index; Leukocyte telomere length; Mild cognitive impairment; Mitochondrial DNA copy number; System inflammation response index; Systemic immune inflammation index. PMID: 36604719 PMCID: PMC9813461 DOI: 10.1186/s12979-022-00326-4