% 0期刊文章%一个雪刘元凯张% %一个凯莉•L•威金斯% Nuzulul Kurniansyah %一个郭Xiuqing %阿曼达L罗德里格%魏赵%丽莎R Yanek %一斯科特•M•拉%蓍属Pitsillides %的胡安·塞巴斯蒂安Aguirre Patino是个说玛开发语的美籍人% % Thomas R .奥斯汀丹大肠发出火花的% %一个Alexa s Beiser % Eric Boerwinkle约翰Blangero % % % 1月布雷斯勒一个乔安妮·e·柯伦%贾丽芳侯%蒂莫西·M·休斯%一个沙龙L Kardia % Lenore Launer % Daniel Levy %一个汤姆·h·莫斯利% Ilya M·纳斯鲁拉% Stephen s .丰富% Sudha Seshadri杰罗姆。无赖%一个% Wassim Tarraf % Vasan凯文·A·冈萨雷斯%一拉马钱德兰% %一个Kristine Yaffe保罗尼奎斯特%一个布鲁斯·查尔斯M Psaty % s DeCarli %詹妮弗·大卫史密斯% C德格拉恩%赫米冈萨雷斯% C约书亚Bis %一个苏珊·R·Heckbert Myriam Fornage % %安妮特·L·菲茨帕特里克%:刘%克劳迪娅·L·Satizabal % T协会的线粒体DNA拷贝数与脑MRI标记和认知功能:一个荟萃分析社区群组% D R 10.1212 / WNL 2023%。0000000000207157 % J半岛投注体育官网神经病学% P 10.1212 / WNL。0000000000207157 X %的背景和目的: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。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. %U //www.ebmtp.com/content/neurology/early/2023/03/15/WNL.0000000000207157.full.pdf