In addition, our MR analyses identified checkpoint regulators BAFFR, C1R, C1Q, CD11, CD19, CD20, CD22, CD33, CD40, CX3CR1, LTBR, PD-1 and PDL-151,57–66 as potential causal risk factors for poor cognitive performance and dementia-causing diseases, uncovering the importance of checkpoint control and potential sources of autoreactivity. Here, C1R is linked to dementia.