‘Dementia gene’ now linked to another devastating neurological disease, study shows

A key Alzheimer’s gene has been revealed to play a role in a second, distinctive brain disorder, revealing a dual threat to cognitive health.

The APOE4 gene, a well-known genetic risk factor for Alzheimer’s disease, has now been identified as an independent risk factor for delirium.

For every copy of the APOE4 gene a person carried, the risk of delirium increased by approximately 60 percent.

This means that someone with one copy has a 1.6 times higher risk, while someone with two copies faces a 2.6 to three times higher risk than someone without an APOE4 copy.

New study from the UK shows that delirium is more than a side effect of existing dementia. This may be an important early warning sign that can effectively accelerate future mental decline, even in people who appear cognitively healthy.

Typically triggered by a serious infection or surgery, delirium causes sudden confusion and disorientation.

Inflammation resulting from these events damages brain cells, the same process that triggers dementia, creating a dangerous biological bridge between the two conditions.

The APOE4 gene makes the brain uniquely susceptible to these inflammatory insults; This discovery opens the door to targeted treatments that could halt this process and prevent delirium from triggering permanent cognitive decline.

This dangerous feedback loop means that a single episode of delirium can permanently alter a patient’s cognitive trajectory.

Acute brain inflammation resulting from delirium not only causes temporary confusion. It actively fuels the same pathological processes that cause long-term neurodegenerative damage.

To identify the link between the Alzheimer’s gene and delirium, researchers combined health and genetic data from more than a million people across several major international biobanks, including the UK Biobank.

Using this large data set, they scanned millions of points in human DNA to identify specific genetic variants associated with a higher risk of delirium.

The team also analyzed blood samples from more than 30,000 people and examined nearly 3,000 proteins years before anyone experienced delirium.

Using advanced machine learning and statistical techniques, they identified which proteins might predict future risk of delirium and investigated whether future drugs could target them.

This risk of experiencing delusions is not just a byproduct of the gene’s link to dementia.

Instead, APOE4 appears to directly weaken the brain’s defenses, making it more susceptible to inflammatory attacks that trigger delirium, such as pneumonia.

This graph shows the results of a genome-wide search for genes linked to delirium. Each dot represents a single DNA change. The x-axis shows its location in the genome, while the y-axis shows the statistical significance of this linkage. The most significant finding was a sudden increase in chromosome 19, which has been described as the APOE gene, identifying it as the strongest genetic risk factor for delirium.

Delirium often occurs as a sudden and noticeable change in a person’s mental state and abilities. A person with delirium He or she may become confused, disoriented, and have significant difficulty focusing or following a conversation.

Their personalities may change and they may become withdrawn, agitated, and suspicious, and they may say nonsensical things or experience hallucinations.

They may have difficulty acting rationally, saying irrational things, or even experiencing hallucinations.

An important sign is a marked decline in their ability to perform routine, daily activities.

Delirium poses a major challenge in healthcare for the elderly.

It affects half of all elderly people in hospital; this number rises to over 70 percent for those in intensive care and affects a significant proportion of up to 60 percent of people in care homes.

The study’s main author, Vasilis Raptis, from the University of Edinburgh, 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.’

A separate, advanced analysis confirmed that a specific region on chromosome 19 that houses the APOE gene plays a central role in delirium.

It highlighted that four specific genes in this region (APOE, TOMM40, PVRL2, and BCAM) are critically involved in the disease process, solidifying this region as a major focus for future research and therapeutic interventions.

Australian actor Chris Hemsworth took a break in 2022 after learning he inherited two copies of APOE4, the so-called ‘Alzheimer gene’, from his parents. Studies show that having both copies increases the risk by 10 to 15 times. Having a copy could double one’s risk

The brain affected by dementia is already in a fragile state and has been weakened by the cumulative damage of the disease.

Neural networks are compromised and the brain has less backup capacity to cope with new stressors.

When a major stressor occurs, such as an infection or surgery, the body’s immune system launches an aggressive attack that further damages the blood-brain barrier, strains brain cells, and can be directly toxic to neurons.

While delirium lasts from hours to a day or two, it causes permanent physical damage by destroying critical nerve connections and actively accelerating disease processes that the brain is already fighting, leading to a more rapid decline.

The results of the England team were published in the magazine Aging of Nature.