Casting light on the links between delirium, infection, and dementia risk

The study by Sarah Pendlebury and colleagues1 merits comment. The authors have addressed the challenge of determining whether there might be a direct association between incidence of delirium or infection and dementia risk in the context of white matter disease. Working with a high-quality dataset, the authors have provided credible evidence that, as found in previous studies,2, 3, 4 the presence of preceding delirium or infection increases subsequent risk of dementia. However, this study contributes new insight by showing that that the effects of delirium and infection on dementia risk were independent of one another, as well as showing the modifying role of white matter disease. Another key contribution of the study is demonstrating the differentiation of the impacts of delirium and infection for older patients (≥80 years) and those who are younger. In particular, the increased dementia risk after delirium was driven mainly by older patients, while the increased risk of dementia after infection was driven by younger patients. In light of the data provided, specific to these modifiable contributing factors for dementia, it is reasonable to conclude that mechanisms mediating dementia in older and younger patients might be entirely disparate or at least sufficiently distinct to warrant further investigation. Building on previous work,5 the authors correctly emphasise that prevention of vascular dementia in patients with white matter disease should focus on post-infection care. Of note, in performing the study, Pendlebury and colleagues have made considerable efforts to work within a well-defined scope of small vessel disease, accessing data for more than 1360 patients. This is no small feat, as the authors have, in effect, mitigated potential confounding by variability in white matter hyperintensities.