Elevated glucocorticoid concentrations, decreased hippocampal volume and frontal atrophy with poor cognitive function have been reported in the elderly but not extensively in Alzheimer's disease (AD). We enrolled 172 patients with AD over a 2-year follow-up period. Basal cortisol levels, biochemistry tests and mini-mental state examination (MMSE) scores were obtained and hippocampal and frontal atrophy were measured by CT scan for correlation. Basal plasma cortisol levels increased with age. Further, basal plasma cortisol levels were correlated with the radial width of the temporal horn, and elevated levels of plasma cortisol predicted a worse general cognitive performance. Higher plasma cortisol levels also correlated with rapid declines in MMSE scores after 2 years. Bilateral frontal atrophy showed no correlation with the above parameters. The relationship between high cortisol levels and hippocampal atrophy might adversely affect AD patients disproportionately, either in anatomical or cognitive function.