Our aim was to evaluate the factorial structure of the mini mental state examination (MMSE) in Alzheimer's disease (AD). Five hundred and twenty-four consecutive outpatients at their first diagnostic work-up (age 78.02+/-6.07 years, education 6.62+/-3.48 years, mean MMSE score 20.23+/-4.89) (+/-S.D.) with probable AD (based on DSM-IV and NINCDS-ADRDA criteria) were enrolled in a multicenter, cross-sectional, regional-based study. For the purpose of the present study, the 11 subtests composing the MMSE and the global MMSE score (ranging from 10 to 29, included) were considered. Factor analysis with Varimax rotation method identified two factors that explained about the 85% of total variance. The first factor explained the 65% of variance and mainly included temporal orientation, delayed recall, attention/concentration, and constructional praxia. The second factor explained the 20% of variance and included reading a sentence, writing a sentence, naming, verbal repetition and immediate memory. The first factor was a reliable index of cognitive deterioration along the MMSE score interval between 29 and 10, whereas the second factor was not a suitable marker in this range. The two-factor structure of the MMSE in AD is shown in a large series of patients. The first factor expresses the ability to use new information and is related with working memory. The second factor is related with a more consolidated knowledge, namely verbal abilities, and is essentially useless in mild to moderate AD.