A recent meta-analysis of 4 studies published up to January 2004 suggests a negative association between coffee consumption and Alzheimer's disease, despite important heterogeneity in methods and results. Several epidemiological studies on this issue have been published since then, warranting an update of the insights on this topic. We conducted a systematic review and meta-analysis of published studies quantifying the relation between caffeine intake and cognitive decline or dementia. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort and case-control studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Nine cohort and two case-control studies were included. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. The outcomes of the studies considered for meta-analysis were Alzheimer's disease in four studies, dementia or cognitive impairment in two studies, and cognitive decline in three studies. The summary relative risk (RR) for the association between caffeine intake and different measures of cognitive iimpairment/decline was 0.84 [95% Confidence Interval (95% CI): 0.72–0.99; I2=42.6%]. When considering only the cohort studies, the summary RR was 0.93 (95% CI: 0.83–1.04, I2= 0.0%), and 0.77 (95% CI: 0.63–0.95, I2= 34.7%), if the most influential study was excluded. This systematic review and meta-analysis found a trend towards a protective effect of caffeine, but the large methodological heterogeneity across a still limited number of epidemiological studies precludes robust and definite statements on this topic. and definite statements on this topic.