@article {Zhang10.1212 / WNL。0000000000207157,作者={刘元凯张和雪和凯莉•L•威金斯Nuzulul Kurniansyah Xiuqing郭和阿曼达·L罗德里格魏赵和丽莎R Yanek和斯科特•m•拉蓍属Pitsillides和胡安·塞巴斯蒂安Aguirre Pati {\ ~ n} o和开发和丹·e·玛发出火花的和托马斯·R·奥斯汀和Alexa Beiser和约翰Blangero和埃里克Boerwinkle和简布瑞斯勒和乔安娜·e·柯伦贾丽芳侯和蒂莫西·m·休斯和沙龙L Kardia Lenore Launer和丹尼尔·利维和汤姆·h·莫斯利和Ilya M. Nasrallah, Stephen S. Rich, Jerome I. Rotter, Sudha Seshadri, Wassim Tarraf, Kevin a . gonzlez, Vasan Ramachandran, Kristine Yaffe, Paul a . Nyquist, Bruce M. Psaty, Charles S. DeCarli, Jennifer a Smith, David C . Glahn, Hector M gonzlez, Joshua C . Bis, Myriam Fornage, Susan R. Heckbert, Annette L. Fitzpatrick, Chunyu Liu, Claudia L. Satizabal，title ={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}，location-id = {10.1212/WNL。0000000000207157}， year = {2023}， doi = {10.1212/WNL。0000000000207157}，出版商= {Wolters Kluwer Health, Inc.代表美国神经病学学会}，摘要={背景和目的:先前的研究表明，较低的线粒体DNA (mtDNA首页)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)和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 {\textpm}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.}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/early/2023/03/15/WNL.0000000000207157}, eprint = {//www.ez-admanager.com/content/early/2023/03/15/WNL.0000000000207157.full.pdf}, journal = {Neurology} }