@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·纳斯鲁拉和Stephen s .丰富杰罗姆。无赖和Sudha Seshadri Wassim Tarraf和凯文·a . Gonz {\ '} lez Vasan拉玛钱德朗和Kristine Yaffe保罗尼奎斯特和布鲁斯·M Psaty和Charles s . DeCarli和詹妮弗·史密斯和大卫·C德格拉恩和赫克托耳M Gonz {\ '} lez和约书亚C Bis和Myriam Fornage和苏珊·R·Heckbert安妮特·L·菲茨帕特里克和刘:克劳迪娅·L·Satizabal} title ={协会的线粒体DNA拷贝数与脑MRI标记和认知功能:一个荟萃分析的以社区为基础的军团},elocation-id = {10.1212 / WNL。={2023}0000000000207157},年,doi = {10.1212 / WNL。出版商0000000000207157}= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={背景和目的:以前的研究表明线粒体DNA (mtDNA)低拷贝数(CN)与神经退半岛投注体育官网行性疾病有关。然而,无论是mtDNA CN在全血与表型的{\ textquoteright}年代老年痴呆症(广告)和广告相关的痴呆(AD / ADRD)需要进一步调查。我们评估协会mtDNA CN与认知功能和MRI措施以社区为基础的样品的中年老年人。方法:我们dementia-free参与者包括来自9个不同社区人群的全基因组测序Trans-Omics精密医学(TOPMed)计划。循环mtDNA CN是估计比率的两倍的平均覆盖率mtDNA核DNA。大脑核磁共振标记包括总,海马,卷和白质高密度。一般认知功能是源于不同的认知领域。我们执行cohort-specific协会分析mtDNA CN广告/ ADRD表型评估{\ textpm} 5年内(即。、横断面分析)或抽血(即后5至20年。、前瞻性分析)调整了潜在的混杂因素。 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.ebmtp.com/content/early/2023/03/15/WNL.0000000000207157}, eprint = {//www.ebmtp.com/content/early/2023/03/15/WNL.0000000000207157.full.pdf}, journal = {Neurology} }