Chronic kidney disease and dementia: an epidemiological perspective

Ageing populations worldwide face increasing challenges of multimorbidity (that is, the co-occurrence of two or more chronic conditions). The combination of chronic kidney disease (CKD) and dementia occurs more frequently than it would by simple coincidence, owing to several underlying biological and clinical mechanisms. Population-based cohort studies are an important epidemiological tool and have contributed to improved understanding of these mechanisms. These mechanisms include uniquely shared haemodynamic features of vasculature, overlapping risk factor profiles, and direct neurotoxic effects of accumulating waste products due to poor kidney function. The effect of these pathways is suggested to differ across gender, relevant demographic subgroups, and populations from low- to middle-income countries. Yet, given their study design, population-based cohort studies also inherently face several methodological challenges. These challenges pertain to the use of biomarkers that do not always fully capture the structure and function of the kidney or the brain; bidirectionality across the pathways under study; and practical issues of proper causal inference in light of incomplete distinction between confounders, mediators and effect modifiers. This Review describes our current understanding of the link between CKD and dementia, with a focus on knowledge synthesized from population-based cohort studies. Methodological challenges and possible solutions will be described and directions for future research areas will be outlined.