Early blood testing to predict dementia is one step closer now that biological markers have been identified

Researchers have taken a major step toward a blood test that can predict the risk of dementia more than a decade before the condition is formally diagnosed in patients.

Hopes for the test were raised after scientists discovered biological markers for the condition in blood samples collected from more than 50,000 healthy volunteers taking part in the UK Biobank project.

Analysis of the blood identified patterns of four proteins that predicted the onset of dementia in general, and Alzheimer’s disease and vascular dementia in particular, in old age.

Combined with more conventional risk factors such as age, sex, education and genetic susceptibility, the protein profiles allowed researchers to predict dementia with an estimated accuracy of 90%, almost 15 years before people received clinical confirmation of the disease.

More than 55 million people worldwide live with dementia, a figure that is expected to reach 78 million by 2030. About 70% of all dementia is caused by Alzheimer’s disease, with vascular dementia, caused by damage to blood vessels, accounting for 20% of cases. .

“We hope to develop this as a screening kit that can be used in the NHS,” says Prof Jianfeng Feng, who holds positions at the University of Warwick and Fudan University in China.

A flurry of recent studies have shown that blood tests may be able to identify patients most likely to develop dementia. Armed with such information, doctors could determine which patients need expedited evaluation for further assessments, including full diagnostic testing for Alzheimer’s disease.

Early confirmation of the disease is crucial if patients are to benefit from two new Alzheimer’s drugs, lecanemab and donanemab, which are currently under review by the UK medicines regulator. If authorized, the National Institute for Health and Care Excellence will consider the costs and benefits before deciding whether to make it available through the NHS.

The US drug regulator, the Food and Drug Administration, has approved lecanemab and is expected to rule on donanemab soon. European regulators are still assessing both drugs.

Since lecanemab, a synthetic antibody therapy developed by Biogen in the US and Eisai in Japan, made headlines in 2022 for slowing Alzheimer’s disease, doctors and medical charities have warned that the healthcare system is not ready to deliver such drugs.

To receive lecanemab or donanemab, patients must have early-stage Alzheimer’s disease and undergo a lumbar puncture or PET scan to confirm the presence of amyloid protein in the brain. Toxic clumps of amyloid are one of the hallmarks of Alzheimer’s disease. But Alzheimer’s Research UK estimates that only 2% of eligible patients undergo such tests.

Efforts are underway to develop and roll out simple blood tests to diagnose Alzheimer’s disease, but even with rapid diagnosis, challenges remain. The new drugs must be given to patients every two weeks, and because of the potentially fatal side effects, patients need regular MRI scans to check for brain swelling or bleeding.

For the latest study, blood samples from 52,645 British adults without dementia were collected and frozen between 2006 and 2010, and analyzed 10 to 15 years later. More than 1,400 participants developed dementia.

Years later, with the help of artificial intelligence, the researchers looked for connections between almost 1,500 blood proteins and the development of dementia. To write Nature agingthey describe how four proteins, Gfap, Nefl, Gdf15 and Ltbp2, were present in unusual amounts among those who developed all-cause dementia, Alzheimer’s disease or vascular dementia.

Higher levels of the proteins were warning signs of disease. Inflammation in the brain can trigger cells called astrocytes to overproduce Gfap, a known biomarker for Alzheimer’s disease. People with elevated Gfap were more than twice as likely to develop dementia than those with lower levels.

Another blood protein, Nefl, is associated with damage to nerve fibers, while Gdf15 can occur higher than normal after damage to the brain’s blood vessels. The rising levels of Gfap and Ltbp2 were highly specific to dementia and not to other brain diseases, the scientists found, with changes occurring at least a decade before people were diagnosed with dementia.

The researchers are speaking to companies to develop the test but say the costs, which are currently several hundred pounds, need to be reduced to make the test viable.

Dr. Sheona Scales, research director at Alzheimer’s Research UK, said: “This new study adds to the growing body of evidence that looking at the levels of certain proteins in the blood of healthy people could accurately predict dementia before symptoms develop. “

Further studies are needed to understand how well such tests work in more diverse populations. Scales added: “Even if tests show promise in studies like this, they still need regulatory approval before they can be used in a healthcare setting.

“Blood tests are promising, but so far none have been validated for use in Britain. In partnership with Alzheimer’s Society, NIHR, and with generous funding from People’s Postcode Lottery players, we are funding research to provide the evidence the NHS needs to move forward with blood testing to treat Alzheimer’s diagnose.”