Alzheimer's Disease (AD) is associated with insulin resistance and low cardiorespiratory fitness, suggestive of impaired skeletal muscle mitochondrial function. We examined if individuals with Mild Cognitive Impairment (MCI), the earliest phase of AD-related cognitive decline, exhibit reduced skeletal muscle mitochondrial function, and if AD medication impacted outcomes. We present data from 50 individuals, including cognitively healthy older adults (CH; n=24) 60+ years of age and clinically diagnosed MCI subjects (n=26). MCI subjects were sub-divided into two groups; no AD medication (MCI; n=11), or AD medication treated (MCI+med; n=15). A skeletal muscle biopsy (vastus lateralis) was obtained and mitochondrial respiratory kinetics was measured in permeabilized muscle fibers. MCI subjects exhibited lower lipid-stimulated skeletal muscle mitochondrial respiration (State 3, ADP-stimulated) than both CH individuals (p=0.043) and medication-treated MCI subjects (p=0.006). MCI also exhibited poorer mitochondrial coupling control compared to CH subjects (p=0.014), while MCI+med and CH subjects did not differ. Compared to CH individuals, skeletal muscle mitochondrial leak control ratio was lower for the MCI+med group (p=0.008) and trended lower for non-medicated MCI (p=0.06), which suggests greater mitochondrial uncoupling in MCI. Skeletal muscle mitochondrial respiration is impaired in untreated MCI but normalized in medication-treated MCI participants while mitochondrial leak control is impaired regardless of medication status. These results provide further evidence that systemic mitochondrial deficits occur in the very early stages of AD, and that mitochondrial function is partially influenced by AD medication. Further analysis for a role of muscle mitochondria in the progression of early AD is warranted.

中文翻译：

---

轻度认知障碍与骨骼肌线粒体缺陷相关

阿尔茨海默氏病（AD）与胰岛素抵抗和低水平的心肺功能相关，提示骨骼肌线粒体功能受损。我们检查了患有轻度认知障碍（MCI），与AD相关的认知功能下降的最早阶段的个体是否表现出骨骼肌线粒体功能降低，以及AD药物是否影响预后。我们提供了来自50个个体的数据，包括60岁以上认知健康的老年人（CH; n = 24）和临床诊断的MCI受试者（n = 26）。MCI主题又分为两组；没有AD药物（MCI; n = 11），或没有经过AD药物治疗（MCI + med; n = 15）。获得骨骼肌活检（外侧输卵管），并测量透化的肌纤维中的线粒体呼吸动力学。与CH个体（p = 0.043）和药物治疗的MCI受试者（p = 0.006）相比，MCI受试者均表现出较低的脂质刺激的骨骼肌线粒体呼吸（状态3，ADP刺激）。与CH受试者相比，MCI还表现出较差的线粒体偶联控制（p = 0.014），而MCI + med和CH受试者没有差异。与CH个体相比，MCI + med组的骨骼肌线粒体泄漏控制率较低（p = 0.008），而非药物MCI的骨骼肌线粒体泄漏控制率则较低（p = 0.06），这表明MCI中线粒体的解偶联作用更大。在未经治疗的MCI中，骨骼肌线粒体呼吸功能受损，但在接受过药物治疗的MCI参与者中，骨骼肌线粒体呼吸功能正常，而无论药物状态如何，线粒体泄漏控制均受损。这些结果提供了进一步的证据，表明系统性线粒体缺陷发生在AD的早期，并且线粒体功能部分受到AD药物的影响。有必要进一步分析肌肉线粒体在早期AD进展中的作用。