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Magnetic resonance elastography (MRE) of the brain has demonstrated potential as a biomarker of neurodegenerative disease such as dementia but requires further evaluation. Cranial anatomical features such as the falx cerebri and tentorium cerebelli membranes may influence MRE measurements through wave reflection and interference and tissue heterogeneity at their boundaries. We sought to determine the influence of these effects via simulation.MRE-associated mechanical stimulation of the brain was simulated using steady state harmonic finite element analysis. Simulations of geometrical models and anthropomorphic brain models derived from anatomical MRI data of healthy individuals were compared. Constitutive parameters were taken from MRE measurements for healthy brain. Viscoelastic moduli were reconstructed from the simulated displacement fields and compared with ground truth.Interference patterns from reflections and heterogeneity resulted in artifacts in the reconstructions of viscoelastic moduli. Artifacts typically occurred in the vicinity of boundaries between different tissues within the cranium, with a magnitude of 10%–20%.Given that MRE studies for neurodegenerative disease have reported only marginal variations in brain elasticity between controls and patients (e.g., 7% for Alzheimer's disease), the predicted errors are a potential confound to the development of MRE as a biomarker of dementia and other neurodegenerative diseases. Magn Reson Med 76:645–662, 2016. © 2015 Wiley Periodicals, Inc.