线粒体DNA拷贝数与脑MRI标记物和认知功能的关联:基于社区队列的meta分析[f - Neurology - JO - Neurology - DO] . 10.1212/WNL.0000000000207157首页Sp - 10.1212/ wnl.0000000000207157AU -张元凯盟雪刘盟-克里•L•威金斯盟Nuzulul Kurniansyah AU -郭Xiuqing盟阿曼达L罗德里格AU -魏赵盟丽莎R Yanek AU -斯科特•m•拉盟蓍属Pitsillides AU -胡安·塞巴斯蒂安Aguirre Patino AU -塔玛开发盟丹大肠发出火花的非盟-托马斯·R·奥斯汀盟Alexa s Beiser AU -约翰Blangero AU -埃里克Boerwinkle盟-简布瑞斯勒非盟-乔安娜·e·柯伦盟贾丽芳侯AU -蒂莫西·m·休斯AU -沙龙L Kardia AU - Lenore Launer AU - Daniel Levy盟——汤姆h·莫斯利AU - Ilya M·纳斯鲁拉盟Stephen s .富盟-杰罗姆。无赖盟Sudha Seshadri盟Wassim Tarraf AU -凯文·A·冈萨雷斯盟Vasan拉玛钱德朗盟Kristine Yaffe盟——保罗尼奎斯特盟——布鲁斯·M Psaty盟——Charles s . DeCarli盟——詹妮弗·史密斯AU -大卫·C德格拉恩AU -赫米冈萨雷斯AU - C约书亚Bis盟Myriam Fornage AU -苏珊·r·Heckbert盟安妮特·l·菲茨帕特里克AU -:刘盟克劳迪娅·l·Satizabal Y1 - 2023/03/16 UR -http://n.首页neurology.org/content/early/2023/03/15/WNL.0000000000207157.abstract N2 -背景和目的:以往的研究表明，较低的线粒体DNA拷贝数(CN)与神经退行性疾病有关。然而，全血mtDNA CN是否与阿尔茨海默病(AD)及AD相关性痴呆(AD/ADRD)的内表型相关，还有待进一步研究。我们评估了mtDNA CN与社区中老年成年人认知功能和MRI测量的关系。方法:我们纳入了来自9个不同社区的无痴呆参与者，并在反式精准医学组学(TOPMed)项目中进行了全基因组测序。循环mtDNA CN估计为mtDNA对核DNA平均覆盖率的两倍。脑MRI标记包括全脑、海马和白质高强度体积。 General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5 to 20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (<60 vs. ≥60 years). Fixed-effects or sample size-weighted meta-analyses were performed to combine results. Finally, we performed Mendelian randomization (MR) analyses to assess causality.Results: We included up to 19,152 participants (mean age 59 years, 57% women). Higher mtDNA CN was cross-sectionally associated with better general cognitive function (Beta=0.04; 95% CI 0.02, 0.06) independent of age, sex, batch effects, race/ethnicity, time between blood draw and cognitive evaluation, cohort-specific variables, and education. Additional adjustment for blood cell counts or cardiometabolic traits led to slightly attenuated results. We observed similar significant associations with cognition in prospective analyses, although of reduced magnitude. We found no significant associations between mtDNA CN and brain MRI measures in meta-analyses. MR analyses did not reveal a causal relation between mtDNA CN in blood and cognition.Discussion:Higher mtDNA CN in blood is associated with better current and future general cognitive function in large and diverse communities across the US. Although MR analyses did not support a causal role, additional research is needed to assess causality. Circulating mtDNA CN could serve nevertheless as a biomarker of current and future cognitive function in the community. ER -