Groundbreaking research from the United Kingdom has uncovered a dangerous dual role for a key Alzheimer's gene, revealing it as a significant and independent risk factor for the acute brain disorder known as delirium.
The Genetic Link Between Delirium and Dementia
Scientists have discovered that the APOE4 gene, a well-established genetic risk factor for Alzheimer's disease, also dramatically increases a person's susceptibility to delirium. This is not merely a side effect of existing dementia but a standalone threat. For each copy of the APOE4 gene a person carries, their risk of experiencing delirium surges by approximately 60 percent.
This translates to a person with one copy having 1.6 times the risk, while an individual carrying two copies faces a substantially higher risk—between 2.6 and three times that of a person with no APOE4 copies.
Delirium as an Early Warning Sign
The new study, which harnessed data from over a million people in international biobanks including the UK Biobank, positions delirium as more than a temporary confusion. It can act as a major early warning sign that actively accelerates future mental decline, even in individuals who appear cognitively healthy.
Typically triggered by a severe infection or surgery, delirium causes sudden confusion, disorientation, and difficulty focusing. The inflammation from these events damages brain cells, mirroring the same process that drives dementia. The APOE4 gene makes the brain uniquely vulnerable to these inflammatory assaults, creating a dangerous biological bridge between the two conditions.
Research Methods and Future Treatments
To pinpoint this link, researchers conducted a genome-wide scan of millions of DNA points. The most significant finding was a spike on chromosome 19, identifying the APOE gene as the strongest genetic risk factor for delirium.
In a separate, advanced analysis, the team also examined blood samples from over 30,000 people, analysing nearly 3,000 proteins years before any of them experienced delirium. Using machine learning, they identified which proteins could predict future delirium risk, opening the door for targeted treatments that could intercept this process and prevent permanent cognitive damage.
Vasilis Raptis, the lead author of the study from the University of Edinburgh, stated: ‘The study provides the strongest evidence to date that delirium has a genetic component. Our next step is to understand how DNA modifications and changes in gene expression in brain cells can lead to delirium.’
The research, published in the journal Nature Aging, confirms that a single episode of delirium can permanently alter a patient's cognitive trajectory, fuelling the pathological processes that cause long-term neurodegenerative damage.
