The role of healthy lifestyle in the association between hepatic fibro-inflammation and steatosis and brain aging—a cross-sectional study

Background This study investigated the association between liver fat, liver fibro-inflammation, and brain age, and assessed whether modifiable lifestyle factors modified the associations between liver markers and brain age. Methods A total of 19,566 adults free from dementia and other neurological disorders were included from the UK Biobank. Liver fat and fibro-inflammation were quantified using proton density fat fraction (PDFF) and iron-corrected T1 mapping (cT1) derived from liver MRI scans. Brain age was estimated using a machine learning model based on 1,079 brain MRI phenotypes, and brain-predicted age difference (brain-PAD) was calculated. Results Among participants, 4,634 (23.7%) had significant steatotic liver disease (PDFF ≥ 5.5%), and 938 (4.8%) had significant fibro-inflammation (cT1 ≥ 800 ms). Both significant liver fat accumulation (β = 0.4, 95% CI: 0.21–0.59) and fibro-inflammation (β = 1.09, 95% CI: 0.74–1.44) were associated with increased brain-PAD. Joint exposure analysis showed that the association between liver fat/fibro-inflammation and increased brain-PAD was attenuated among individuals with healthy lifestyle choices. Conclusion Liver fat accumulation and fibro-inflammation were associated with higher brain-PAD, with fibro-inflammation playing a key role. These associations may be attenuated in individuals with optimal lifestyle behaviors, suggesting a potentially modifiable target for intervention.