We compared two methods of measuring cerebral atrophy in a cohort of 38 clinically probable Alzheimer's disease (AD) subjects and 22 age-matched normal controls, using metrics of zero atrophy, consistency, scaled atrophy and AD/control group separation. The two methods compared were the boundary shift integral (BSI) and a technique based on the integration of Jacobian determinants from non-rigid registration. For each subject, we used two volumetric magnetic resonance (MR) scans at baseline and a third obtained 1 year later. The case of zero atrophy was established by registering the same-day baseline scan pair, which should approximate zero change. Consistency was established by registering the 1-year follow-up scan to each of the baseline scans, giving two measurements of atrophy that should be very similar, while scaled atrophy was established by reducing one of the same-day scans by a fixed amount, and rigidly registering this to the other same-day scan. Group separation was ascertained by calculating atrophy rates over the two 1-year measures for the control and AD subjects. The results showed the Jacobian integration technique was significantly more accurate in calculating scaled atrophy (P < 0.001) and was able to distinguish between control and AD subjects more clearly (P < 0.01).