‘A Profound Change’: New Guidelines Proposed for Diagnosing Alzheimer’s

A new way of defining for Alzheimer’s could help patients receive an early and accurate diagnosis. Clinicians presented a draft of a new definition and diagnosing criteria at the Alzheimer’s Association International Conference in July 2023 to request feedback from others in the field. Scientists say it could be a huge leap forward for the field.

Like many other diseases, Alzheimer’s has evolved from a cluster of clinical observations and symptoms into one characterized by specific biological features — protein plaques and inflammation. 

“Instead of calling Alzheimer’s a disease where you forget your glasses and keys and repeat yourself, now we’re defining it by inflammation, amyloid, and tau,” Dr. Marwan Sabbagh, a clinician and professor of neurology at the Barrow Neurological Institute, told Being Patient. “It’s a profound change to our field.”

The new definition presented at AAIC focuses on biomarkers, making it possible for someone to receive a diagnosis even if they have no symptoms or family history of the disease — provided they test positive for these biomarkers. 

“There’s continuing evidence that biomarkers can explain the natural history of the disease,” Jason Karlawish, professor of medicine at the University of Pennsylvania, told Being Patient. He added that the success of Leqembi further validated these biomarkers — the anti-amyloid treatment that slowed the progression of the disease by lowering the levels of beta-amyloid plaques. 

New Alzheimer’s diagnostic standards, better Alzheimer’s care

For diseases like diabetes, doctors will intervene early at signs of a troubling biomarker like high blood sugar. “We don’t wait for them to have renal failure, retinal damage, small vessel or disease in their feet,” Karlawish said. Medications that treat high blood sugar, like insulin, can prevent many of the complications of the disease. 

In the case of Alzheimer’s, the problem has always been the burden of getting the diagnosis. Expensive amyloid PET scans weren’t covered by Medicare until recently (the VA also provides coverage), while a lumbar puncture is invasive and painful. 

Both Sabbagh and Karlawish foresee that blood tests will make their way into clinical practice within the next few years, allowing more people to get a fast, affordable diagnosis. With a diagnosis in hand, patients can join clinical trials for new potential drugs and receive a prescription for Leqembi. 

“I think primary care physicians don’t feel comfortable making a diagnosis of Alzheimer’s,” Sabbagh said. “But they do feel comfortable managing blood test values all day long, so this might help them that way.”

However, not everyone favors the changes to the definition and diagnostic criteria for Alzheimer’s. Alberto Espay, a professor of neurology at the University of Cincinnati, told Being Patient that the biomarkers for Alzheimer’s aren’t specific enough — beta-amyloid, tau, and inflammation also crop up across many other neurodegenerative conditions. He added that the blood tests have “limited clinical usefulness” beyond research. 

Early diagnosis matters.

According to the new diagnostic criteria, someone in their 30s or 40s who has high levels of beta-amyloid or tau in their blood could be labeled as having Alzheimer’s disease. “That label would be made solely on the basis of biological measures, absent any kind of clinical symptoms or cognitive losses or functional impairment,” Karlawish said. 

While family doctors won’t be testing young patients for Alzheimer’s out of the blue, it may be essential to consider the implications of this decision. Direct-to-consumer tests are hitting the market for better or worse: Young people may find out that they have Alzheimer’s based on these biomarkers. 

“What’s the value of that? And I think it’s a pretty legitimate ethics question for individual and public policy questions for society.” It can be stressful to receive the diagnosis since there is no way to cure the disease at the moment, only a way to slow its progress. 

Alzheimer’s science continues to evolve

When Alois Alzheimer first characterized the disease in 1906, there was no way to measure beta-amyloid plaques before death. For almost a century, clinicians and researchers relied on symptoms to make the diagnosis — often at the later stages. 

Advances in technology led to changes in the definition of Alzheimer’s in 2011, recognizing less severe stages of the disease, including mild cognitive impairment. Now, some scientists hope it may be possible to get a diagnosis even sooner thanks to the widespread application of blood tests. 

But no biomarker is perfect. Many people with these biomarkers will never develop the symptoms of Alzheimer’s disease. 

In one study published in JAMA Neurology in 2018, researchers assessed how many cognitively healthy older individuals had the toxic plaque in their brains for 15 months. Out of 1,671 cognitively healthy people aged 80 to 89, about 43 percent were “amyloid positive.” Other studies looking at cognitively healthy individuals post-mortem find that one in four have beta-amyloid plaques in their brain. 

However, Sabbagh is optimistic that there will be more advances in the future, which will help make the diagnosis even more accurate. “We are going to be able to differentiate the different protein [plaques] at a molecular level of the protein,” Sabbagh said. This will allow clinicians to narrow down Alzheimer’s into subtypes further, improving both diagnosis and treatment outcomes.