Alzheimer’s and delirium: Scientists have identified a direct genetic link between delirium in hospital patients and a gene already known for its strong association with Alzheimer’s disease.
In a large genetic analysis involving more than one million people from the UK, Finland and the US, researchers found that a variant of the APOE gene, long recognised as a major risk factor for Alzheimer’s, also independently raises the risk of delirium. The work was led by a team at the University of Edinburgh and published in the journal Nature Ageing.
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APOE is responsible for producing a protein that helps transport cholesterol and other fats in the bloodstream. One version of this gene, called APOE e4, is known to increase the chance of developing Alzheimer’s, a progressive brain disease that affects memory, thinking and decision-making.
The new study shows that APOE e4 has its own, separate role in delirium risk and that this effect cannot be explained away by its link to dementia alone. Even after researchers adjusted their analysis to account for dementia, APOE still showed a strong association with delirium, suggesting it contributes to confusion and acute mental change in people who do not have dementia.
The team combined genetic data from several large cohorts, including the UK Biobank, FinnGen, the All of Us Research Program and the Michigan Genomics Initiative, in what they describe as a multi-ancestry genetic meta-analysis. This highlighted APOE as a key risk gene for delirium, independent of dementia status.
To go further, the scientists examined blood samples from around 32,000 UK Biobank participants who later developed delirium; the samples had been collected up to 16 years before diagnosis. They identified several proteins in the blood linked to future delirium risk, including markers related to brain injury and inflammation.
The researchers say the findings point to a biological basis for delirium involving brain vulnerability and inflammatory processes in both the nervous system and the rest of the body. They also suggest that shared genetic pathways between delirium and Alzheimer’s may help explain why an episode of delirium so often precedes or accelerates longer-term cognitive decline.
The team now plans to investigate how changes in DNA regulation and gene activity in brain cells might trigger delirium, with the hope of improving prediction, prevention and treatment of this common and serious condition.