Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurology, Weill Cornell Medicine, New York, New York, USA.
Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Eur J Neurol. 2022 Sep;29(9):2622-2630. doi: 10.1111/ene.15437. Epub 2022 Jun 20.
There is growing recognition that chronic liver conditions influence brain health. The impact of liver fibrosis on dementia risk was unclear. We evaluated the association between liver fibrosis and incident dementia in a cohort study.
We performed a cohort analysis using data from the UK Biobank study, which prospectively enrolled adults starting in 2007, and continues to follow them. People with a Fibrosis-4 (FIB-4) liver fibrosis score >2.67 were categorized as at high risk of advanced fibrosis. The primary outcome was incident dementia, ascertained using a validated approach. We excluded participants with prevalent dementia at baseline. We used Cox proportional hazards models to evaluate the association between liver fibrosis and dementia while adjusting for potential confounders.
Among 455,226 participants included in this analysis, the mean age was 56.5 years and 54% were women. Approximately 2.17% (95% confidence interval [CI] 2.13%-2.22%) had liver fibrosis. The rate of dementia per 1000 person-years was 1.76 (95% CI 1.50-2.07) in participants with liver fibrosis and 0.52 (95% CI 0.50-0.54) in those without. After adjusting for demographics, socioeconomic deprivation, educational attainment, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with an increased risk of dementia (hazard ratio 1.52, 95% CI 1.22-1.90). Results were robust to sensitivity analyses. Effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status was not observed.
Liver fibrosis in middle age was associated with an increased risk of incident dementia, independent of shared risk factors. Liver fibrosis may be an underrecognized risk factor for dementia.
人们越来越认识到慢性肝脏疾病会影响大脑健康。肝纤维化对痴呆风险的影响尚不清楚。我们在一项队列研究中评估了肝纤维化与痴呆发病风险之间的关系。
我们使用英国生物库研究的数据进行了队列分析,该研究于 2007 年开始前瞻性招募成年人,并持续对他们进行随访。肝纤维化-4(FIB-4)评分>2.67 的人被归类为有进展性肝纤维化的高风险人群。主要结局是通过经过验证的方法确定的痴呆发病。我们排除了基线时患有痴呆的参与者。我们使用 Cox 比例风险模型来评估肝纤维化与痴呆之间的关联,同时调整了潜在的混杂因素。
在本分析中纳入的 455226 名参与者中,平均年龄为 56.5 岁,54%为女性。约有 2.17%(95%置信区间[CI]2.13%-2.22%)存在肝纤维化。肝纤维化患者每 1000 人年的痴呆发生率为 1.76(95%CI1.50-2.07),无肝纤维化患者为 0.52(95%CI0.50-0.54)。在调整了人口统计学、社会经济剥夺、教育程度、代谢综合征、高血压、糖尿病、血脂异常以及烟草和酒精使用情况后,肝纤维化与痴呆风险增加相关(风险比 1.52,95%CI1.22-1.90)。敏感性分析结果稳健。未观察到性别、代谢综合征和载脂蛋白 E4 携带状态的效应修饰。
中年肝纤维化与痴呆发病风险增加相关,与共同的危险因素无关。肝纤维化可能是痴呆的一个被低估的危险因素。