The aim of the present study was to examine the relationship between cerebral morphological changes and cognitive deficits as determined by the CERAD neuropsychological test battery in a large group of patients with MCI and with AD and otherwise healthy elderly controls. Patients were recruited among typical memory clinic referrals and carefully matched for age, gender and educational level. Optimized voxel based morphometry was used to reveal gray matter differences between groups and to investigate the association of neuropsychological deficits with brain structural alterations. When compared to controls, AD patients and, to a lesser extent, patients with MCI showed significant atrophy predominantly in the medial temporal lobe. Deficits in verbal fluency and word finding were significantly correlated with left fronto-temporal and left temporal (including the hippocampus) changes, respectively. Decreased scores in immediate and delayed recall and in delayed recognition were associated with several cortical and subcortical areas including the parahippocampal and posterior cingulate gyrus, the right thalamus, and the right hippocampus, whereas deficits in constructional praxis and constructional praxis recall referred to regions in the left thalamus and cerebellum, and the temporal cortices, respectively. These findings lend further support to medial temporal lobe degeneration in MCI and AD and suggest that cognitive deficits reflect morphological alterations in widespread cortico-subcortical networks.