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<p>Blood-based biomarkers are increasingly used to characterize Alzheimer’s disease (AD)–related pathology, yet substantial heterogeneity exists in how biomarker burden relates to cognitive performance. Grip strength, a marker of frailty and functional reserve, may modify this relationship. We conducted a cross-sectional analysis of 348 participants from the Aging Adult Brain Connectome (AABC) study. Global cognition was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Plasma biomarkers included phosphorylated tau-217 (pTau<sub>217</sub>), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total tau (tTau). Multiple linear regression models tested biomarker × grip strength interactions, adjusting for demographic factors, APOE ε4 status, cardiometabolic risk factors, body mass index, and creatinine. Sensitivity analyses included age-based propensity score matching and age-stratified models. Participants with low PACC were older, had lower grip strength, and higher plasma biomarker levels than those with normal cognition (all <i>p</i> &lt; 0.001). In adjusted models, significant interactions between low grip strength and biomarkers were observed for pTau<sub>217</sub> (β =  − 0.046, <i>p</i> &lt; 0.01), NfL (β =  − 0.002, <i>p</i> &lt; 0.001), and GFAP (β =  − 0.005, p &lt; 0.05). Age-matched showed attenuation of some interaction effects except for low grip strength and NfL. Age-stratified analyses showed a significant interaction for NfL among adults ≥ 65&#xa0;years and for GFAP among those &lt; 65&#xa0;years. Grip strength moderated the association between plasma AD-related biomarkers and cognitive performance, supporting physical strength as an indicator of vulnerability. Integrating simple strength measures with blood biomarkers may improve cognitive risk stratification in community-dwelling adults.</p>

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Grip strength modifies the association between blood-based alzheimer’s biomarkers and cognitive function

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月11日

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  • Semere Bekena,
  • Ramkrishna K. Singh,
  • Yiqi Zhu,
  • Jean-Francois Trani,
  • Beau M. Ances,
  • Ganesh M. Babulal

摘要

Blood-based biomarkers are increasingly used to characterize Alzheimer’s disease (AD)–related pathology, yet substantial heterogeneity exists in how biomarker burden relates to cognitive performance. Grip strength, a marker of frailty and functional reserve, may modify this relationship. We conducted a cross-sectional analysis of 348 participants from the Aging Adult Brain Connectome (AABC) study. Global cognition was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Plasma biomarkers included phosphorylated tau-217 (pTau217), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total tau (tTau). Multiple linear regression models tested biomarker × grip strength interactions, adjusting for demographic factors, APOE ε4 status, cardiometabolic risk factors, body mass index, and creatinine. Sensitivity analyses included age-based propensity score matching and age-stratified models. Participants with low PACC were older, had lower grip strength, and higher plasma biomarker levels than those with normal cognition (all p < 0.001). In adjusted models, significant interactions between low grip strength and biomarkers were observed for pTau217 (β =  − 0.046, p < 0.01), NfL (β =  − 0.002, p < 0.001), and GFAP (β =  − 0.005, p < 0.05). Age-matched showed attenuation of some interaction effects except for low grip strength and NfL. Age-stratified analyses showed a significant interaction for NfL among adults ≥ 65 years and for GFAP among those < 65 years. Grip strength moderated the association between plasma AD-related biomarkers and cognitive performance, supporting physical strength as an indicator of vulnerability. Integrating simple strength measures with blood biomarkers may improve cognitive risk stratification in community-dwelling adults.