Strengths and limitations
The strengths of this systematic review and meta-analysis were: i) applying a comprehensive search strategy; ii) taking the explicit criteria for inclusion of interested studies; iii) using strict statistical methods for analyses; iv) employing the preferred methodology of systematic review and meta-analysis;21, 22 v) performing the test of publication bias with multiple methods.
The limitations of this study were also impossible to ignore, including that: i) the pooled RR was synthesized from the results of observational studies which presented plausible confounding factors decreasing the strength of observed effect. Therefore, the findings should be interpreted with caution; ii) a high degree of heterogeneity was presented, which can’t be interpreted from a single study because the sensitivity analyses using a leave-one-out method didn’t change the direction of effect. In this study, the origin of heterogeneity may mainly result from the study design, i.e. the low heterogeneity in the prospective studies. However, other factors like races of patients, follow-up duration, the observational window, may importantly impact the heterogenous effects of OAC use on risk of dementia.