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Gordon Romero, Danilo Tali

University of British Columbia

Background: Advances in clinical practice over the past several decades have increased the median lifespan for individuals living with severe congenital heart disease (CHD) by almost 20 years. As a result, the demographics of this population have evolved such that two-thirds of individuals living with CHD are adults. While the majority of CHD research has focused on cardiac and neurodevelopmental outcomes, recent findings suggest that adults with CHD are at an increased risk of dementia, and cross-sectional studies in younger cohorts indicate an elevated risk of neurocognitive impairment. These observations highlight the need for research investigating the pathological effects of CHD on brain health, as it is still unknown whether these deficits are driven by early-life insults, ongoing accumulating injury, or both. This study measured serum concentrations of neurofilament-light (NfL), a marker of neuronal injury, and glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, in a cohort of 93 adults with moderate-severe CHD. Methods: Participants from an existing longitudinal brain health study of adults with moderate-severe CHD underwent cognitive tests, MRI scans, and blood draws. Serum samples were analyzed for NfL/GFAP using the Simoa HD-X and compared to age-adjusted reference intervals (RI) using Fisher’s Exact test. Multivariable regressions, including demographic and clinical variables, were performed to investigate associations between NfL/GFAP and quantitative neuroimaging data. Results: Of 93 participants, 40% were above the 95th percentile RI for GFAP and 6% were above the 95th percentile RI for NfL. More individuals above the GFAP RI had white matter hyperintensities (WMH) on MRI (p=0.008, OR=3.6). Individuals with WMH had significantly higher NfL concentrations than those without (p=0.0077). Regression analysis found that increased biomarker levels were associated with reduced total brain volume (NfL, p=0.038; GFAP, p=0.013), and reduced white matter volume (WMV) (NfL, p=0.022; GFAP, p=0.006). Conclusions: In this study, NfL levels were elevated in individuals with CHD who have WMH on MRI, and increased biomarker levels were associated with reduced total brain volume and total white matter volume. This hypothesis-generating work provides preliminary insights into potential pathophysiological mechanisms for incidental brain imaging abnormalities that are common in adults with CHD.

Text

2024-08-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89121

Pathology and Laboratory Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/