Ceolin Chiara, Gregorio Caterina, Ornago Alice Margherita, Grande Giulia, Valletta Martina, Trevisan Caterina, Casla Adrián Carballo, Sergi Giuseppe, Calderón-Larrañaga Amaia, Vetrano Davide Liborio
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Aging Research Center, Stockholm, Sweden.
Geriatrics Division, Department of Medicine (DIMED), University of Padua, Padua, Italy.
J Cachexia Sarcopenia Muscle. 2025 Jun;16(3):e13835. doi: 10.1002/jcsm.13835.
Sarcopenia is a complex and multifactorial condition, and recent studies have explored the role of neurological markers in its diagnosis and prediction. Although associations have been identified between reduced muscle strength, slow walking speed and elevated neurofilament levels (NfL), long-term evidence and sex-based differences in muscle health and sarcopenia remain underexplored. This study investigates the relationship between baseline blood biomarkers of Alzheimer's disease (AD) and long-term sarcopenia trajectories in a Swedish cohort of older adults, while also examining potential sex-based differences.
The study analysed 2291 participants aged ≥ 60 years (61.5% females) over a 12-year follow-up, classifying sarcopenia into three stages (no, probable and confirmed sarcopenia) using modified EWGSOP2 criteria. Muscle strength was assessed via handgrip or chair stand tests and muscle mass via calf circumference. Baseline data on AD biomarkers were collected. Latent class mixed models identified two sarcopenia trajectories: one with early progression accelerating around age 70 years and another with later progression accelerating after age 80 years, observed in both sexes. Regression analyses examined the associations between AD biomarkers, sarcopenia progression speed and incidence.
Probable and confirmed sarcopenia were more prevalent in females (28.2% vs. 14.1% and 7.6% vs. 6.1%, respectively; p < 0.001). All AD biomarkers showed significantly different distributions across the three sarcopenia stages. Analysis revealed that only p-tau181 (OR 1.24 [1.09; 1.42], p = 0.002) and NfL (OR 1.56 [1.30; 1.91], p < 0.001) were independently associated with worse sarcopenia trajectories. These associations remained significant in individuals over 78 years (p-tau181: OR 1.32 [1.11; 1.59], p = 0.003; NfL: OR 1.77 [1.40; 2.28], p < 0.001) and in males (p-tau181: OR 1.39 [1.14; 1.73], p = 0.003; NfL: OR 1.38 [1.11; 1.82], p < 0.001). In females, only NfL remained significantly associated. NfL was significantly linked to sarcopenia development (HR 1.20 [1.10; 1.30], p < 0.001), with similar findings for females (HR 1.40 [1.20; 1.63], p < 0.001) and older individuals (HR 1.35 [1.15; 1.58], p < 0.001). Notably, both NfL and p-tau181 were significantly associated with sarcopenia incidence in younger participants (< 78 years) and in males, independent of dietary patterns.
Our study, unique for its long follow-up duration, explores the relationship between sarcopenia and neurodegeneration biomarkers, highlighting the role of p-tau181 and NfL in the progression of the condition. These biomarkers could potentially serve as indicators for the early detection of sarcopenia, particularly in older adults and males, offering insights that may contribute to personalized screening and targeted interventions.
肌肉减少症是一种复杂的多因素病症，最近的研究探讨了神经学标志物在其诊断和预测中的作用。尽管已发现肌肉力量下降、步行速度减慢与神经丝水平（NfL）升高之间存在关联，但关于肌肉健康和肌肉减少症的长期证据以及基于性别的差异仍未得到充分研究。本研究调查了瑞典老年人群队列中阿尔茨海默病（AD）的基线血液生物标志物与长期肌肉减少症轨迹之间的关系，同时还研究了潜在的性别差异。
该研究分析了2291名年龄≥60岁的参与者（61.5%为女性），随访时间为12年，使用改良的EWGSOP2标准将肌肉减少症分为三个阶段（无、可能和确诊肌肉减少症）。通过握力或椅子站立测试评估肌肉力量，通过小腿围评估肌肉质量。收集了关于AD生物标志物的基线数据。潜在类别混合模型确定了两种肌肉减少症轨迹：一种是在70岁左右加速的早期进展轨迹，另一种是在80岁以后加速的后期进展轨迹，在男女中均有观察到。回归分析检验了AD生物标志物、肌肉减少症进展速度和发病率之间的关联。
可能和确诊的肌肉减少症在女性中更为普遍（分别为28.2%对14.1%和7.6%对6.1%；p<0.001）。所有AD生物标志物在三个肌肉减少症阶段的分布均有显著差异。分析显示，只有p-tau181（OR 1.24[1.09；1.42]，p=0.002）和NfL（OR 1.56[1.30；1.91]，p<0.001）与更差的肌肉减少症轨迹独立相关。在78岁以上的个体中（p-tau181：OR 1.32[1.11；1.59]，p=0.003；NfL：OR 1.77[1.40；2.28]，p<0.001）和男性中（p-tau181：OR 1.39[1.14；1.73]，p=0.003；NfL：OR 1.38[1.11；1.82]，p<0.001），这些关联仍然显著。在女性中，只有NfL仍然显著相关。NfL与肌肉减少症的发展显著相关（HR 1.20[1.10；1.30]，p<0.001），女性（HR 1.40[1.20；1.63]，p<0.001）和老年人（HR 1.35[1.15；1.58]，p<0.001）的结果相似。值得注意的是，NfL和p-tau181均与较年轻参与者（<78岁）和男性的肌肉减少症发病率显著相关，与饮食模式无关。
我们的研究因其较长的随访时间而独特，探讨了肌肉减少症与神经退行性变生物标志物之间的关系，突出了p-tau181和NfL在该病症进展中的作用。这些生物标志物可能潜在地作为肌肉减少症早期检测的指标，特别是在老年人和男性中，提供可能有助于个性化筛查和靶向干预的见解。
