Wang Jiao, Yang Rongrong, Miao Yuyang, Zhang Xinjie, Paillard-Borg Stéphanie, Fang Zhongze, Xu Weili
Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Liver Int. 2025 Jun;45(6):e70109. doi: 10.1111/liv.70109.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to cognitive decline and dementia risk. We aimed to investigate the association between MASLD and brain ageing and explore the role of low-grade inflammation.
Within the UK Biobank, 30 386 chronic neurological disorders-free participants who underwent brain magnetic resonance imaging (MRI) scans were included. Individuals were categorised into no MASLD/related SLD and MASLD/related SLD (including subtypes of MASLD, MASLD with increased alcohol intake [MetALD] and MASLD with other combined aetiology). Brain age was estimated using machine learning by 1079 brain MRI phenotypes. Brain age gap (BAG) was calculated as the difference between brain age and chronological age. Low-grade inflammation (INFLA) was calculated based on white blood cell count, platelet, neutrophil granulocyte to lymphocyte ratio and C-reactive protein. Data were analysed using linear regression and structural equation models.
At baseline, 7360 (24.2%) participants had MASLD/related SLD. Compared to participants with no MASLD/related SLD, those with MASLD/related SLD had significantly larger BAG (β = 0.86, 95% CI = 0.70, 1.02), as well as those with MASLD (β = 0.59, 95% CI = 0.41, 0.77) or MetALD (β = 1.57, 95% CI = 1.31, 1.83). The association between MASLD/related SLD and larger BAG was significant across middle-aged (< 60) and older (≥ 60) adults, males and females, and APOE ɛ4 carriers and non-carriers. INFLA mediated 13.53% of the association between MASLD/related SLD and larger BAG (p < 0.001).
MASLD/related SLD, as well as MASLD and MetALD, is associated with accelerated brain ageing, even among middle-aged adults and APOE ɛ4 non-carriers. Low-grade systemic inflammation may partially mediate this association.
代谢功能障碍相关脂肪性肝病（MASLD）与认知能力下降和痴呆风险相关。我们旨在研究MASLD与脑老化之间的关联，并探讨低度炎症的作用。
在英国生物银行中，纳入了30386名未患慢性神经疾病且接受过脑磁共振成像（MRI）扫描的参与者。个体被分为无MASLD/相关脂肪性肝病（SLD）组和MASLD/相关SLD组（包括MASLD的亚型、酒精摄入量增加的MASLD[MetALD]和具有其他合并病因的MASLD）。通过1079种脑MRI表型利用机器学习估计脑龄。脑龄差距（BAG）计算为脑龄与实际年龄之差。基于白细胞计数、血小板、中性粒细胞与淋巴细胞比值和C反应蛋白计算低度炎症（INFLA）。使用线性回归和结构方程模型分析数据。
在基线时，7360名（24.2%）参与者患有MASLD/相关SLD。与无MASLD/相关SLD的参与者相比，患有MASLD/相关SLD的参与者的BAG显著更大（β = 0.86，95%置信区间 = 0.70，1.02），患有MASLD的参与者（β = 0.59，95%置信区间 = 0.41，0.77）或MetALD的参与者（β = 1.57，95%置信区间 = 1.31，1.83）也是如此。MASLD/相关SLD与更大BAG之间的关联在中年（<60岁）和老年（≥60岁）成年人、男性和女性以及APOE ε4携带者和非携带者中均显著。INFLA介导了MASLD/相关SLD与更大BAG之间关联的13.53%（p < 0.001）。
MASLD/相关SLD以及MASLD和MetALD与脑老化加速相关，即使在中年成年人和APOE ε4非携带者中也是如此。低度全身炎症可能部分介导这种关联。
