From an individual patient management standpoint, this study highlights a number of clinically relevant points. First, to be clinically meaningful, a change in MMSE score during any period must exceed 3 points. This threshold makes it more likely that the difference reflects an actual change in cognitive abilities rather than testing imprecision. Second, the MMSE, when used as the sole measure of cognitive change for an individual patient, may not be a reliable measure for intervals of less than 3 years. Procedures that might enhance the utility of the MMSE as a measure of change are not obvious. Other structured instruments for measuring cognitive change in patients with dementia have similar limitations. From a practical standpoint, a clinician may want to continue to use the MMSE, particularly if the assessment can be done often enough to allow averaging of the changes that may be due to random variation. Although not assessed in this study, clinicians should always consider other factors that may affect individual MMSE scores, such as changes in the patient's living environment, medications, and the presence of problem behaviors. In addition, changes in a patient's functional abilities and the observations of a knowledgeable caregiver are important components in reaching an overall conclusion about changes in dementia severity. Third, the rate of change in MMSE score is not influenced to a clinically meaningful extent by the age at onset of dementia symptoms or the presence of relatively mild medical comorbidity. Furthermore, in this cohort, neither age at the time of assessment nor sex contributed to (or predicted) either the annual rate of MMSE score change or the variability associated with that annual change. Fourth, although the hallmark of AD is progressive cognitive impairment, the rate of change for individual patients varies, and it is not uncommon for patients to have a stable or even an improved score during a 1-year interval. Although we have found that the degree of variation narrows with increasing length of follow-up, this may simply reflect a self-censoring process associated with drop out as patients are admitted to a nursing home, become too severely impaired to return for follow-up evaluations, or die.