NAFLD患者における全脳容積の減少

非アルコール性脂肪性肝疾患（NAFLD）が脳の老化を早める可能性があることを示唆するデータが、イスラエルなどのグループによりJAMA Neurol（2018; 75: 97-104）に発表された。

NAFLDはメタボリックシンドローム、糖尿病、頸動脈硬化症、血管内皮障害など脳障害や認知障害につながる状態と関係がある。しかし、NAFLDが脳の構造に影響を与えるかどうかは明らかではない。同グループは、NAFLDと脳MRI所見との関係を検討した。

　対象は、米国のフラミンガム研究の第二世代コホートで、登録時に過度の飲酒習慣および脳卒中と認知症がなかった766例（女性410例、男性356例、脳MRI検査時の平均年齢67歳）。NAFLDは腹部CT検査で評価した。共変量として年齢、性、飲酒・喫煙習慣、内臓脂肪量、BMI、閉経状態、血圧、コレステロール値、インスリン抵抗性、C反応性蛋白値など多くの因子を補正した。

　766例中137例（17.9％）がNAFLDと診断された。解析の結果、全ての共変量を補正後もNAFLDは全脳容積の小ささと有意な関係を示した（β＝－0.26、P＝0.02）。NAFLD患者と非NAFLD患者の全脳容積の差は一般サンプルで4.2年の脳老化に相当し、60歳未満では7.3年の老化に相当した。

Association of Nonalcoholic Fatty Liver Disease With Lower Brain Volume in Healthy Middle-aged Adults in the Framingham Study.

Weinstein G, Zelber-Sagi S, Preis SR, Beiser AS, DeCarli C, Speliotes EK, Satizabal CL, Vasan RS, Seshadri S.

JAMA Neurol. 2018 Jan 1;75(1):97-104. doi: 10.1001/jamaneurol.2017.3229.

Abstract

IMPORTANCE:

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.

OBJECTIVE:

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.

EXPOSURES:

Nonalcoholic fatty liver disease was assessed by multidetector computed tomographic scans of the abdomen.

MAIN OUTCOMES AND MEASURES:

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.

RESULTS:

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.

CONCLUSIONS AND RELEVANCE:

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.

PMID: 29159396 PMCID: PMC5833484 [Available on 2018-11-20] DOI: 10.1001/jamaneurol.2017.3229