Gene linked to delirium highlighted by large-scale study

A major genetic risk factor for delirium has been identified in a study analysing the DNA of over one million people worldwide. 

The gene, already associated with Alzheimer’s disease, increases the risk of developing delirium, a condition marked by sudden mental confusion, research found. 

The newly found effect is not solely due to the gene’s link with dementia, indicating the gene also has a direct role in delirium, experts note.

Researchers from the Roslin Institute collaborated with colleagues from the University of Edinburgh’s Usher Institute and School of Mathematics to conduct the largest and most diverse genetic analysis of delirium to date, drawing on data from the UK, US, and Finland. 

The discovery creates opportunities for targeted treatments and for preventing progression from delirium to dementia.

Delirium affects around one in four hospitalised older adults and is associated with increased mortality, longer hospital stays, and a two- to three-fold rise in future dementia risk. 

Despite its impact, no specific treatments currently exist. The gene, known as APOE, increased delirium risk even in people without dementia, providing strong evidence that its influence is independent of dementia.

Researchers also identified genetic overlap with Alzheimer’s risk genes, which may help explain why delirium can precede or accelerate cognitive decline. 

In addition, blood samples from 32,000 people who developed delirium – collected by UK Biobank up to 16 years before diagnosis – revealed several blood-based proteins that can predict delirium risk, including markers of brain injury and inflammation, some newly associated with the condition.

The findings highlight new treatment possibilities. One protein, PON3, was linked with protection against delirium and may be a promising target for drugs. 

PON3 is thought to be involved in the metabolic processing of some cholesterol-lowering drugs, called statins, suggesting these existing medicines might be repurposed to help lower delirium risk, although experts say further research is needed.

The study is published in Nature Aging and was funded by the Vivensa Foundation and Legal & General Group. Data was provided by UK Biobank, FinnGen, the All of Us Research Programme, and the Michigan Genomics Initiative. 

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