Blood biomarkers of Alzheimer’s disease and 12-year muscle strength trajectories in community-dwelling older adults: a cohort study
Authors: Alice M Ornago, Elena Pinardi, Giulia Grande, Martina Valletta, Amaia Calderón-Larrañaga, Sarah Andersson, Riccardo Calvani, Anna Picca, Emanuele Marzetti, Bengt Winblad, Claudia Fredolini, Giuseppe Bellelli, Davide L Vetrano
Journal: The Lancet Healthy Longevity (2025)

Age-related muscle function decline is a major impediment to healthy ageing. We aimed to investigate the association between a panel of Alzheimer's disease-related biomarkers and longitudinal trajectories of muscle strength, while exploring the influence of cognitive function. In this cohort study, we gathered data from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), an ongoing prospective study that includes adults aged 60 years and older, from central Stockholm, Sweden. We included data from baseline to the fourth follow-up (March 21, 2001, to Dec 31, 2016). Seven Alzheimer's disease-related blood biomarkers were measured in dementia-free, community dwelling participants: total tau, phosphorylated tau181 (p-tau181), phosphorylated tau217 (p-tau217), amyloid β 40 and 42, neurofilament light chain, and glial fibrillary acidic protein (GFAP). Muscle strength was measured through the handgrip strength and chair-stand tests. Linear mixed models were used to explore the association between baseline Alzheimer's disease-related biomarkers and muscle strength trajectories. The baseline SNAC-K cohort included 3363 individuals, of whom 1953 participants were included in our analyses (mean age 70·2 [SD 9·1] years; 780 [39·9%] male and 1173 [60·1%] female participants). In adjusted models, higher concentrations of p-tau181 (β per year 0·93 [95% CI 0·71 to 1·16]; p<0·0001), p-tau217 (β per year 1·31 [1·03 to 1·58]; p<0·0001), neurofilament light chain (β per year 0·76 [0·56 to 0·96]; p<0·0001), and GFAP (β per year 0·37 [0·21 to 0·53]; p<0·0001) were associated with an accelerated decline of chair-stand performance over time. The adjustment for Mini-Mental State Examination (MMSE) score led to the attenuation of these associations. Higher concentrations of p-tau181 (β per year -0·12 [95% CI -0·17 to -0·07]; p<0·0001), p-tau217 (β per year -0·13 [-0·20 to -0·07]; p<0·0001), and neurofilament light chain (β per year -0·05 [-0·09 to -0·001]; p=0·047) were also associated with faster handgrip strength decline, with no attenuation after adjusting for MMSE score. Sex-specific differences were observed, with female participants showing a stronger association between biomarker concentrations and muscle strength decline than male participants, particularly in the chair-stand test. Our findings suggest that blood Alzheimer's disease-related biomarkers might help estimate progressive muscle strength decline among older adults, elucidating the influence of brain pathology and cognitive ageing on this association. These Alzheimer's disease-related biomarkers could aid in identifying individuals for early intervention to prevent sarcopenia. The Swedish Research Council, the Swedish Ministry of Health and Social Affairs, and the County Councils and Municipalities.