This study investigated the relationship between Life's Essential 8 (LE8), a recently updated lifestyle-related health factor, and cognition across multiple life stages. We enrolled 1098 cognitively normal participants from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. We investigated the interactions between age and LE8 on cognition. Multiple linear regression models were utilized to explore the relationship between the LE8 total scores and its two subscales scores with cognition in the total sample, as well as in the mid-age (≤65 years) and the late-age (>65 years) subgroups. In addition, mediation analyses were performed to explore the biologically plausible pathways between LE8 and cognition. There was a significant interaction effect between age and LE8 total scores on MOCA score (P = 0.030). The mid-age subgroup showed a positive correlation between LE8 total scores and CM-MMSE (β = 0.110, P = 0.005) and MOCA (β = 0.112, P = 0.005) scores. However, no significant associations were found in the late-age subgroup. In the mid-age subgroup, CSF p-tau partially mediated the relationship between LE8 total scores and its two subscales and cognition, with a mediation proportion ranging from 6% to 12%. Our findings revealed that the association of the LE8 total scores with MOCA and CM-MMSE scores were significant in mid-age adults rather than late-age adults, indicating that the association might be age-specific and emphasizing the importance of lifestyle interventions in mid-life.
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