The improvement in cognitive performances due to cholinesterase inhibitors (ChEls) is not homogeneous among Alzheimer's disease (AD) subjects. Aim of this study is to evaluate whether a specific pattern of change in mini mental state examination (MMSE) could be observed in AD subjects after 9-month treatment with ChEls. From September 2000 to September 2002, 99 subjects enrolled in the CRONOS project. They have never been previously treated with ChEls. All of them completed both the 3- and the 9-month follow-up. The multidimensional assessment included MMSE, activity of daily living (ADL), instrumental activity of daily living (IADL), somatic health status, according to design of the CRONOSproject. The MMSE was analyzed both as a total score and disaggregated in 11 items. All subjects were divided in 2 groups according to the degree of change in MMSE total score from baseline to the 9th month. Subjects with a change </= -1 were defined as non-responders(NR), whereas those with a change >0 as responders (R). At start, no statistically significant differences were found between the 2 groups. MMSE score was significantly higher in the R group both at 3 (p < 0.0001) and 9 months (p < 0.0001), while functional status (ADL and IADL) was significantly lower in NR group at 9 months (p = 0.025; p =0.018, respectively). In MMSE qualitative analysis of 3-month, NR significantly worsened in temporal (p </= 0.05) and spatial orientation (p </= 0.001), and in delayed recall items (p </= 0.0005) in comparison to their counterpart. At 9-month the differences between the 2 groups were observed also for registration (p < 0.001), attention (p </= 0.0005), obeying oral commands (p < 0.0005), reading and obeying commands (p </= 0.0005), writing a sentence (p </= 0.0005) and copying a design (p </= 0.05). In a multivariate regression model, after adjustment for demographic (age, education, gender) and clinical factors (duration of disease), only the change at 3 months in 5 MMSE items (temporal and spatial orientation,delayed recall, obeying an oral command and reading and obeying command) is associated with global cognitive change observed at 9 months. Data suggest that the change in cognitive performances of AD subjects treated with ChEls involves few and specific MMSE items at 3-month, while it tend to generalize to almost all the others at 9-month treatment.