Risk of delirium, a state of confusion commonly experienced by hospitalised patients, has been independently, directly linked to a gene well-known to contribute towards Alzheimer's disease, according to an analysis of more than a million people from across the UK, Finland and the US.
Gene "APOE" is known to make a protein that helps carry cholesterol and other fats in the blood. Having the gene variant "APOE e4" is said to increase one's risk of developing the ageing-related Alzheimer's disease, in which thought processes and decision-making are steadily impacted over time.
However, the gene has a distinct, direct role to play in causing delirium, and one's risk of experiencing delirium cannot be solely explained by the gene's link to Alzheimer's disease, researchers from the University of Edinburgh said.
Findings published in the journal Nature Ageing show that the effects of the APOE gene on risk of delirium held despite adjusting for dementia, thereby providing strong evidence that the gene contributes to the risk in people without dementia.
The overlap between genetic risks of delirium and Alzheimer's disease may help explain why delirium so often precedes or accelerates cognitive decline, the researchers said.
"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," said co-author of the study, Vasilis Raptis from the University of Edinburgh.
The researchers "conducted a genetic meta-analysis on delirium using multi-ancestry data from the UK Biobank, FinnGen, All of Us Research Program and Michigan Genomics Initiative cohorts, yielding the Apolipoprotein E (APOE) gene as a strong delirium risk factor independently of dementia." Blood samples from 32,000 individuals in the UK Biobank who developed delirium, collected up to 16 years before a diagnosis, were also analysed.
They identified proteins that can help predict delirium risk years before developing symptoms, which included markers of brain injury and inflammation.
"The findings shed new light on the biological foundations of delirium, suggesting that brain vulnerability, systemic and nervous system inflammation may all play important roles," co-author Albert Tenesa, professor of quantitative genetics at the University of Edinburgh, said.
"This opens new avenues for investigation not just of delirium itself, but also the poorly understood and very important link between delirium and future risk of dementia," Tenesa added.
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