Non-alcoholic fatty liver disease associated with brain volume loss in middle-aged individuals

1. In this cross-sectional study of middle-aged adults, radiologic evidence of non-alcoholic fatty liver disease (NAFLD) was associated with reduced total cerebral brain volume (TCBV) as measured by MRI.

2. The estimated brain aging linked with NAFLD was greater for younger patients and the association became less significant in older participants.

Evidence Rating Level: 3 (Average)    

Study Rundown: The prevalence of NAFLD is rising world-wide and represents the most common cause of chronic liver disease in older adults. Some studies and animal models have suggested a link between NAFLD and cognitive decline, thought in part to be due to shared risk factors. However, some investigations have suggested a more causal relationship with hepatic inflammation and hepatokine release on adverse brain health. As NAFLD is amenable to lifestyle intervention and may represent a modifiable risk factor, understanding the relationship between NAFLD and brain function is important. The current study is a cross-sectional analysis that explored the relationship between radiographic NAFLD and brain volume as measured by MRI. The study demonstrated that NAFLD was linked to decreased TCBV even after accounting for known covariates. The estimated effect on brain age was greater for younger patients.

The current study provides evidence for a possible connection between NAFLD and brain health that may be more than just shared risk factors.  The study used a population of patients with well-studied cardiovascular parameters and may be important for generating hypotheses for further studies. It is limited by the reliance of radiographic rather than biopsy proven NAFLD or functional cognitive testing, homogenous nature of the population, and cross-sectional design limiting evaluation of causation.

Click to read the study, published in JAMA Neurology

Relevant Reading: Non-alcoholic fatty liver disease and cerebral small-vessel disease in cognitively normal individuals

In-Depth [cross-sectional study]: This study is a cross-sectional analysis of the offspring cohort of the Framingham Heart Study which evaluated participants between 2002 and 2005. Participants were excluded if they were younger than 35 years (men) or 40 years (women), consumed more than 14 (men) or 7 (women) alcoholic beverages a week, were greater than 160 kgs, had established dementia, or if CT scans of the abdomen, or MRI of the brain were not available.

There were 766 participants included in the study, and 137 (17.9%) had CT evidence of NAFLD. NAFLD was linked to reduced TCBV after adjustment for known covariates (β [SE], –0.26 [0.11]; p = 0.02). Estimated for brain age loss was 7.3 years for participants under 60 years, 4.2 years for those aged 60-74, and 1.5 years for those 75 years of older.

Image: PD

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