We thank the authors for their interest in our study and for their comments on the brain reserve hypothesis. We agree that adult intracranial volume is likely to be influenced by both genetic factors and environmental influences in utero and during early development. Metabolic or other "insults" during this crucial period may affect both final intracranial volume and ultimate IQ and therefore result in a relationship between head size and IQ. However, we feel it does not necessarily follow that an individual's head size or TIV will influence the development of a degenerative disorder such as AD, with its own complex interplay of genetic and environmental etiological factors.1 It may be that a relationship exists between intracranial volume and risk of SAD, but our study and others that measured TIV2,3 did not find evidence of such a relationship.
Fox NC, Jenkins R, Rossor M. In reply. Arch Neurol. 2001;58(5):831-833. doi: