School of Public Health, University of Haifa, Haifa, Israel.
Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel.
JAMA Neurol. 2018 Jan 1;75(1):97-104. doi: 10.1001/jamaneurol.2017.3229.
Nonalcoholic fatty liver disease (NAFLD) is a common condition that is most often asymptomatic. It is associated with metabolic syndrome, incident diabetes, carotid atherosclerosis, and endothelial dysfunction, conditions that in turn are strongly linked with brain damage and cognitive impairment. However, it is not known whether NAFLD is associated with structural brain measures in humans.
To assess the association between prevalent NAFLD and brain magnetic resonance imaging (MRI) measures.
DESIGN, SETTING, AND PARTICIPANTS: The cross-sectional association between NAFLD and brain MRI measures was assessed from November 6, 2002, to March 16, 2011, in 766 individuals from the Offspring cohort of the Framingham Study. Participants were included if they did not have excessive alcohol intake and were free of stroke and dementia. Data analysis was conducted from December 30, 2015, to June 15, 2016.
Nonalcoholic fatty liver disease was assessed by multidetector computed tomographic scans of the abdomen.
Linear or logistic regression models were used to evaluate the cross-sectional association between NAFLD and brain MRI measures, adjusting for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, hypertension, current smoking, high-density lipoprotein and low-density lipoprotein cholesterol levels, lipid treatment, type 2 diabetes, cardiovascular disease, physical activity, insulin resistance, C-reactive protein levels, and plasma homocysteine values. Brain MRI measures included total cerebral brain volume, hippocampal and white matter hyperintensity volumes, and presence or absence of covert brain infarcts.
Of the 766 individuals in the study sample (410 women and 356 men; mean [SD] age at the time of brain MRI, 67 [9] years), 137 (17.9%) had NAFLD. Nonalcoholic fatty liver disease was significantly associated with smaller total cerebral brain volume even after adjustment for all the covariates included in the study (β [SE], -0.26 [0.11]; P = .02). Differences in total cerebral brain volume between those with and without NAFLD corresponded to 4.2 years of brain aging in the general sample and to 7.3 years in individuals younger than 60 years of age. No statistically significant associations were observed between NAFLD and hippocampal or white matter hyperintensity volumes or covert brain infarcts.
Nonalcoholic fatty liver disease is associated with a smaller total cerebral brain volume, independent of visceral adipose tissue and cardiometabolic risk factors, pointing to a possible link between hepatic steatosis and brain aging.
非酒精性脂肪性肝病（NAFLD）是一种常见病症，通常没有症状。它与代谢综合征、新发糖尿病、颈动脉粥样硬化和内皮功能障碍有关，而这些病症又与大脑损伤和认知障碍密切相关。然而，目前尚不清楚 NAFLD 是否与人类的大脑结构测量有关。
评估现患非酒精性脂肪性肝病与脑磁共振成像（MRI）测量值之间的关联。
设计、地点和参与者：这项来自弗雷明汉研究后代队列的 766 名个体的横断面研究，于 2002 年 11 月 6 日至 2011 年 3 月 16 日评估了 NAFLD 与脑 MRI 测量值之间的关联。如果个体没有过量饮酒且没有中风和痴呆，则将其纳入研究。数据分析于 2015 年 12 月 30 日至 2016 年 6 月 15 日进行。
通过腹部多层计算机断层扫描评估非酒精性脂肪性肝病。
采用线性或逻辑回归模型评估 NAFLD 与脑 MRI 测量值之间的横断面关联，调整因素包括年龄、性别、饮酒量、内脏脂肪组织、体重指数、绝经状态、收缩压、高血压、当前吸烟状况、高密度脂蛋白和低密度脂蛋白胆固醇水平、降脂治疗、2 型糖尿病、心血管疾病、身体活动、胰岛素抵抗、C 反应蛋白水平和血浆同型半胱氨酸水平。脑 MRI 测量值包括总脑容量、海马和脑白质高信号容积以及隐匿性脑梗死的存在或缺失。
在研究样本中（410 名女性和 356 名男性；脑 MRI 时的平均[标准差]年龄为 67[9]岁），137 人（17.9%）患有 NAFLD。即使在调整了研究中包含的所有协变量后，非酒精性脂肪性肝病仍与较小的总脑容量显著相关（β[SE]，-0.26[0.11]；P=0.02）。在一般样本中，有无 NAFLD 之间的总脑容量差异相当于大脑老化 4.2 年，而在年龄小于 60 岁的个体中相当于大脑老化 7.3 年。NAFLD 与海马或脑白质高信号容积或隐匿性脑梗死之间未观察到统计学显著关联。
非酒精性脂肪性肝病与总脑容量较小有关，与内脏脂肪组织和心血管代谢危险因素无关，这表明肝脂肪变性与大脑衰老之间可能存在联系。
