Abstract P007: Liver Biomarkers And Brain Health: The Atherosclerosis Risk In Communities (aric) Study

Introduction: Animal studies and emerging population data link liver function and integrity to brain health, although mostly based on cross-sectional estimates. We reported that low liver transaminases are associated with risk of dementia, but prospective studies on liver biomarkers and altered brain morphology are lacking. Methods: We studied 1,596 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort examined in 1996-98 (mean age: 62 years, 59% female, 27% Black) free of chronic liver disease, cirrhosis, and stroke, and with alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio ≤2. Brain magnetic resonance imaging (MRI) scans were performed in 2011-13, at the time of re-examination. Serum transaminases (ALT, AST) and gamma-glutamyl transferase (GGT) at baseline were analyzed as sex-specific quintiles, with the first quintile further subdivided into a th and 10 th -20 th percentiles to allow for nonlinear associations at low biomarker levels. Brain MRI markers were measured with 3 Tesla MRI. Multinomial logistic and linear regressions were used, adjusted for demographics and APOE-ε4. Results: Monotonic associations were observed between higher GGT levels and smaller cortical volume and temporal lobe volume meta regions of interest (Figure) . The lowest GGT levels were associated with smaller volumes of white matter hyperintensities. In contrast, associations of transaminases with brain morphological measures were inconclusive. Conclusions: GGT levels measured in late mid-life are associated vascular sequelae on brain MRI among older adults. As a potent regulator of antioxidant capacity and a predictor of atherosclerosis, GGT may point to vascular pathways that influence brain health. The lack of association between low transaminases and brain MRI findings suggests non-vascular pathways for their association with incident dementia. A deeper understanding of the links between hepatic metabolic dysregulation and brain health is warranted.