Sir, Many thanks for letting us respond to the interesting letter concerning our recent paper. We are grateful for the chance to clarify the points raised, which suggest our conclusions were too optimistic. In our paper (Kloppel et al. , 2008), we used MRI scans from pathologically proven cases of Alzheimer's disease and frontotemporal lobar degeneration (FTLD) to validate trained sets for a machine learning-based support vector machine (SVM) approach to the categorization of structural scans from normal and each other. This rigorous approach substantially limited the number of available subjects, which we made perfectly clear in our article, but which was unavoidable given our novel approach. Frost and colleagues are right to point out that such low numbers result in larger confidence intervals than if we were able to include more scans. This is an object of our further empirical studies—what is the improvement in classification gained using this technique with greater numbers of scans in the trained set? The graph below (Fig. 1 …