OBJECTIVES: The risk of bradycardia and its consequences from use of cholinesterase inhibitors (ChI) in dementia was reported in epidemiological studies in 2009 and from a case series for memantine in 2008. We compared the detection and timing of these associations between disproportionality analysis and published epidemiological studies.  METHODS: We conducted 1) a systematic review of the literature to identify epidemiological studies reporting AEs in patients taking currently prescribed ChI and memantine, and 2) an analysis in the FDA spontaneous Adverse Event Reporting System database (AERS) using the Empirical Bayesian Geometric Mean (EBGM) statistic and 90% credibility intervals (90%CI),  to allow for low frequencies of drug-event pairs. A composite event consisted of any of the following: bradycardia, bradyarrythmia, pacemaker insertion, complete atrio-ventricular block and hip and femoral fracture. AEs from all drugs in AERS was the comparator.   RESULTS: A total of 246 cases suspected of being associated with ChI and the composite event were identified. A statistically strong signal of disproportionate reporting, adjusted for age, sex and year was observed (EBGM of 6.58, 90%CI: 5.79 – 7.47). Cumulative yearly analyses revealed that the signal became statistically strong in 1997, one year after approval of the first currently used ChI. The first signal was reported in an epidemiological study in 2009. For memantine, 69 suspected cases were identified with the composite event. A statistically strong signal of disproportionate reporting, adjusted for age, sex and year, was observed (EBGM of 1.87; 90%CI: 1.47 – 2-38). Cumulative yearly analyses revealed that the signal became statistically strong and stable two years after the first reported composite event. No epidemiological studies have yet been published.    CONCLUSIONS: Analysis of suspected events can be followed over time and may detect, confirm or refute drug-event signals much earlier than epidemiological studies and inform health technology assessments.