A new definition of Alzheimer’s disease could radically change how Alzheimer’s is diagnosed and treated.

Guidelines published in the April issue of Alzheimer’s & Dementia reframe the Alzheimer’s diagnosis according to biological markers, or “biomarkers.” But this redefinition will be confined right now for the purpose of research, not for patients.  

According to the new guidelines, an Alzheimer’s disease diagnosis will now be based on three main biomarkers: the buildup of beta-amyloid proteins (plaques), tau proteins (tangles), and neurodegeneration.

“The new definition is an attempt to better explain why you might have cognitive problems, number one,” said Dr. Jason Karlawish, a professor of medicine in the division of geriatrics at University of Pennsylvania and one of the authors of the guidelines. “And number two, to give physicians the opportunity to prescribe treatments that might slow down or even prevent you from developing those cognitive problems.”

According to the latest figures from the Alzheimer’s Association, 5.7 million Americans are living with the disease, which currently has no cure.

A change for researchers

The new definition of the disease diagnosis comes with a large caveat: It’s exclusively for the purposes of research into the disease.

A clinical diagnosis for patients will still be made according to signs and symptoms, such as progressive memory loss and a decline in the ability to think.

To diagnose the disease using biomarkers right now, a person has to have a spinal tap or a positron emission tomography (PET) scan — both difficult procedures that carry a lot of risk.

“There is expense and burden and risk that comes with getting these biomarkers,” said Nancy Hodgson, PhD, RN, an associate professor of nursing at University of Pennsylvania who wasn’t involved in drawing up the new guidelines. Because of the risk involved, until someone shows clear symptoms of the disease, they’re unlikely to be tested for the presence of these biomarkers.

“One of the things that the research will need to work out in the coming decades is who would we approach and say, ‘I want to do tests for Alzheimer’s biomarkers on you, because you might have them, and I have an intervention to offer you,’” said Karlawish.

The reason for this change for researchers is to enable more clinical trials for drugs that target these specific biomarkers, said Karlawish.

Biomarkers but no symptoms

Complicating Alzheimer’s disease diagnoses is the fact that not everyone with biomarkers of the disease show symptoms. And not everyone with symptoms have clear biomarkers of the disease.

Right now, there are a handful of trials going on in people that have Alzheimer’s biomarkers but who don’t meet the clinical criteria for dementia. One good example is the A4 study, said Karlawish. In this study, participants have been identified as having amyloid buildups in their brain after a PET scan, but they don’t have cognitive decline.

Researchers are testing a drug that targets these plaques to see if it’ll keep some groups of people from exhibiting dementia symptoms in the future.

It’s been estimated that about a third of people who have received an Alzheimer’s diagnosis don’t have plaques and tangles or neurological changes in their brains. This means that drugs targeting these biomarkers may not show any effects for these patients, potentially muddying the results of a clinical trial.

“I think there is a lot of excitement, both for finding the cure, and also for continuing to work in this area where now we will have the right patients in the right studies based on the biology of the disease,” said Hodgson.

One consequence of that is that people who’d previously receive an Alzheimer’s diagnosis now won’t be classed as having the disease, and others who wouldn’t have received a diagnosis now will be.

“These new criteria are going to change who has Alzheimer’s,” said Karlawish.

The problems of an early Alzheimer’s disease diagnosis

“One area that needs research and also some reflection — not just by researchers but also by society — is the disease experience of people with preclinical Alzheimer’s disease,” said Karlawish. “Not because they have a cognitive problem that people are noticing getting in the way of their daily life, but because they have a test that says they are going to develop dementia down the road.”

Karlawish said that giving someone this diagnosis today can make them rethink their life and their future, since there’s no current cure for Alzheimer’s disease.

“If I tell a busy 66-year-old management consultant that he has Alzheimer’s disease, I think that busy management consultant would start to think about himself differently, about his future — and the people he tells that result to will probably think differently about him and his future,” said Karlawish.

Despite these concerns, Hodgson said a new definition will help achieve two of the key goals of the research community: develop a test that’s easier to administer for Alzheimer’s and to find new treatments for the disease.

If new criteria or tests for an Alzheimer’s disease diagnosis is validated in future research studies, then clinicians can start to use them in their practice. But that research still needs to be done.

“I’m sure that this shift will stimulate research dollars and that will only result in an acceleration of the pipeline,” said Hodgson.

For people who have Alzheimer’s or something that appears to be akin to it, speed may be of the essence.

“It is still a progressive disease with no cure. A lot of people are fearful. This is the most feared diagnosis,” said Hodgson. “We all are in this because we want to find the cure for these people. But at the same time, we want to recognize that there are individuals living with the disease right now.”