Objectives: To estimate the annual rate of change scores (ARC) on the Mini-Mental State Examination (MMSE) in Alzheimer's disease (AD) and to identify study or population characteristics that may affect the ARC estimation. Methods: MEDLINE was searched for articles published from January 1981 to November 1997 using the following keywords: AD and longitudinal study or prognosis or cognitive decline. The bibliographies of review articles and relevant papers were searched for additional references. All retrieved articles were screened to meet the following inclusion criteria: (a) original study; (b) addressed cognitive decline or prognosis or course of AD; (c) published in English; (d) study population included AD patients with ascertainable sample size; (e) used either clinical or pathological diagnostic criteria; (f) longitudinal study design; and (g) used the MMSE as one of the outcome measures. Data were systematically abstracted from the included studies, and a random effects regression model was employed to synthesize relevant data across studies and to evaluate the effects of study methodology on ARC estimation and its effect size. Results: Of the 439 studies screened, 43 met all the inclusion criteria. After 6 studies with inadequate or overlapping data were excluded, 37 studies involving 3,492 AD patients followed over an average of 2 years were included in the meta-analysis. The pooled estimate of ARC was 3.3 (95% confidence interval [CI]: 2.9-3.7). The observed variability in ARC across studies could not be explained with the covariates we studied, whereas part of the variability in the effect size of ARC could be explained by the minimum MMSE score at entry and number of assessments. Conclusions: A pooled average estimate of ARC in AD patients was 3.3 points (95% CI: 2.9-3.7) on the MMSE. Significant heterogeneity of ARC estimates existed across the studies and cannot be explained by the study or population characteristics investigated. Effect size of ARC was related to the initial MMSE score of the study population and the number of assessments.