LAUSR

Physical frailty and cognitive frailty share biological mechanisms, but sex-specific biomarkers associated with transitions in gait speed and cognition during ageing are poorly understood.Gait speed, cognition (3MSE), body composition (DXA) and serological biomarkers were assessed annually over 9 years in 216 males (72.7 + 8.07 years) and 384 females (71.1  +  8.44 years). In females, maintaining normal gait speed was associated with lower percent body fat (IRR 0.793, p  = 0.001, 95%CI 0.691–0.910) and lower lactate dehydrogenase (LDH) (IRR 0.623, p = 0.00, 95%CI 0.514–0.752), and in males, the association was with higher cholesterol (IRR 1.394, p  = 0.001, 95%CI 1.154–1.684). Abnormal to normal gait speed transitions were associated with higher insulin in females (IRR 1.325, p  = 0.022, 95%CI 1.041–1.685) and lower creatinine in males (IRR 0.520, p  = 0.01, 95%CI 0.310–0.870). Normal to slow gait speed transitions in males were associated with IGF-1 (IRR 1.74, p  = 0.022, 95%CI 1.08–2.79) and leptin in females (IRR 1.39, p  = 0.043, 95%CI 1.01–1.91.) Maintaining normal cognition was associated with lower LDH in females (IRR 0.276, p  = 0.013, 95%CI 0.099–0.765) and higher appendicular skeletal muscle mass in males (IRR 1.52, p  = 0.02, 95%CI 1.076–2.135). Improved cognition was associated with higher leptin (IRR 7.5, p  = 0.03, 95%CI 1.282–44.34) and lower triglyceride (IRR 0.299, p  = 0.017, 95%CI 0.110–0.809) in males. Education was protective against cognitive decline in females (IRR 0.84, p = 0.037, 0.732–0.982). Sex-specific biomarkers of muscle (LDH, Creatinine, IGF-1, APSM) and metabolism (%fat, insulin,cholesterol, leptin, tryglycerides) were associated with gait speed and cognitive transitions. These data suggest that modifiable biomarkers of muscle and metabolism could be targeted for interventions.