Background: Subclinical liver disease may be a risk factor for cognitive impairment. Obesity is related to metabolic processes that affect brain structures underlying cognitive decline. Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition with high cardiovascular disease (CVD) morbidity. In a population-based cross-sectional sample of black and white adults free from prevalent liver or cerebrovascular disease, we tested the hypothesis that NAFLD is associated with early measures of brain health independent of BMI or visceral adipose tissue (VAT).
Methods: Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and brain magnetic resonance (MR) images were included. NAFLD was defined after exclusion of other causes of liver fat. 3T brain MR images provided estimates of normal tissue volume (NTV) and total (CBF-tot) and gray matter (CBF-GM) cerebral blood flow. NTV was adjusted for intracranial volume (ICV, brain plus cerebral spinal fluid). CBF was adjusted for total tissue volume (TTV, total brain tissue perfused). Linear regression models tested associations.
Results: Mean liver attenuation (LA) was 56.9 HU (range 16.6-81.3). NAFLD prevalence was 11%. Lower LA (higher liver fat) was associated with reduced NTV, CBF-tot and CBF-GM after adjusting for ICV, demographics, and health behaviors (p<0.05). LA remained associated with CBF-tot and CBF-GM after adjustment for CVD factors (p<0.05). Only NTV was significant after adjustment for CVD factors and BMI (p=0.02). After adjusting for VAT, the relationship between LA and NTV was attenuated (p=0.06). Findings were similar when using a clinical cutpoint of ≤51 HU for NAFLD (Table 1).
Conclusion: Increased liver fat and CT-defined NAFLD are negatively associated with early brain health, reflected in MR measures of structure and perfusion. BMI and VAT attenuate the relationship providing insight into the potential role of obesity in brain health and disease.