SAN DIEGO – The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.
The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.
During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.
The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
Guidance for clinical trials and memory clinics
The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.
The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.
However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.
The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.
Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.
In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.