Association of Alzheimer's Disease Blood Biomarkers With Sarcopenia Incidence and Progression: A 12-Year Population-Based Study

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Alzheimer disease; blood biomarkers; neurodegeneration; older adults; protein intake; sarcopenia.

FIGURE 1

Distribution of the blood biomarkers of Alzheimer's disease by sarcopenia categories at baseline. Notes: Box plots show the median (central line) and interquartile range (box) as well as the 2.5th and 97.5th percentiles (whiskers). p values are derived from Kruskal–Wallis test; *: < 0.05; **: < 0.01; ***: < 0.001; ****: < 0.0001. Aβ42/40 amyloid‐beta 42/40; GFAP, glial fibrillary acidic protein; NfL, neurofilament light chain; p‐tau181, phosphorylated‐tau181; t‐tau, total‐tau.

FIGURE 2

Latent profiles of sarcopenia progression stratified by sex: colour‐coded representation of early progression trajectory (yellow) and late progression trajectory (blue). Notes: The figure displays the median (solid line) and 95% confidence interval (shade).