RT期刊文章SR电子T1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摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯10.1212 SP / WNL。半岛投注体育官网0000000000207157 10.1212 / WNL。0000000000207157 A1刘薛元凯张A1 A1克里•L•威金斯A1 Nuzulul Kurniansyah A1 Xiuqing郭A1阿曼达L罗德里格A1魏赵A1丽莎R Yanek A1斯科特•M•拉A1蓍属Pitsillides A1胡安·塞巴斯蒂安Aguirre Patino A1开发A1丹·e·玛发出火花的A1 Thomas R .奥斯汀A1 Alexa s Beiser A1约翰Blangero A1埃里克Boerwinkle A1简布瑞斯勒A1乔安妮·e·柯伦A1贾丽芳侯A1蒂莫西·M·休斯A1沙龙L Kardia A1 Lenore Launer A1 Daniel Levy A1汤姆·h·莫斯利A1 Ilya M·纳斯鲁拉A1 Stephen s .丰富A1杰罗姆。无赖A1 Sudha Seshadri A1 Wassim Tarraf A1凯文·A·冈萨雷斯A1 Vasan拉马钱德兰A1 Kristine Yaffe A1保罗尼奎斯特A1布鲁斯·M Psaty A1 Charles s . DeCarli A1珍妮弗·史密斯A1 David C德格拉恩A1赫米冈萨雷斯A1约书亚C Bis A1 Myriam Fornage A1苏珊·R·Heckbert A1安妮特·L·菲茨帕特里克A1:刘A1克劳迪娅·L·Satizabal年2023 UL //www.ebmtp.com/content/early/2023/03/15/WNL.0000000000207157.abstract AB背景和目的:以前的研究表明线粒体DNA (mtDNA)低拷贝数(CN)与神经退行性疾病有关。半岛投注体育官网然而,无论是mtDNA CN在全血与表型的阿尔茨海默病(AD)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±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。我们进一步探讨协会分层按性别和年龄(< 60岁和≥60岁)。 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.