The evaluation of atrophy quantification methods based on magnetic resonance imaging have been usually hindered by the lack of realistic gold standard data against which to judge these methods or to help refine them. Recently [Camara, O., Schweiger, M., Scahill, R., Crum, W., Sneller, B., Schnabel, J., Ridgway, G., Cash, D., Hill, D., Fox, N., 2006. Phenomenological model of diffuse global and regional atrophy using finite-element methods. IEEE Trans. Med.l Imaging 25, 1417-1430], we presented a technique in which atrophy is realistically simulated in different tissue compartments or neuroanatomical structures with a phenomenological model. In this study, we have generated a cohort of realistic simulated Alzheimer's disease (AD) images with known amounts of atrophy, mimicking a set of 19 real controls and 27 probable AD subjects, with an improved version of our atrophy simulation methodology. This database was then used to assess the accuracy of several well-known computational anatomy methods which provide global (BSI and SIENA) or local (Jacobian integration) estimates of longitudinal atrophy in brain structures using MR images.