New Developments on the Alzheimer’s Disease Diagnostic Front — Part I

In July, we attended the Alzheimer’s Association International Conference in London. The big news at the meeting was on the diagnostics front.  In the aftermath of the recent string of trial failures, diagnostic tools have become a critical area of focus, in the hopes that patient diagnosis and selection can be improved.

 

Accurately diagnosing Alzheimer’s disease has always been problematic, with no definitive diagnosis possible except by autopsy after the patient’s death. Diagnosis to date has primarily looked at a patient’s symptoms and how they change over time.

 

Research results from two different studies grabbed the news spotlight around the conference, as they both confirm that many patients are misdiagnosed as having Alzheimer’s and suggest potential strategies for identifying those patients at true risk, years before cognitive symptoms emerge.

 

The first reported data from the first 4,000 people tested to date in the ongoing Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study, conducted in the United States and Europe. The aim of the study was to examine over 18,000 patients with mild cognitive impairment (MCI) or dementia by means of PET scanning to see if their brains contain amyloid plaques, one of two hallmarks of the disease (the other being the Tau protein). The researchers found that 54.3% of the MCI patients and 70.5% of the dementia patients had the plaques. This finding could change the way that doctors treat people in these hard-to-diagnose groups; up to 60% of the physicians participating in the study planned to change the way they managed their PET-scanned patients.

 

The second study, conducted by a team from the Washington University School of Medicine in St. Louis, Missouri, reported on the potential for developing a rapid, inexpensive blood-based screening test for amyloid-beta. The researchers looked at the levels of three different subtypes of amyloid-beta found in blood of 41 people age 60 and older. They found that levels of amyloid-beta 42, relative to amyloid-beta 40, were consistently 10-15% lower in people confirmed (by PET scan) to have amyloid plaque deposition in their brains or Alzheimer’s disease associated amyloid alterations in their cerebrospinal fluid. The amyloid plaques that characterize Alzheimer’s disease are composed primarily of amyloid-beta 42; the researchers theorized that the protein was probably being deposited in the patients’ brains before moving in the bloodstream.

 

By averaging the ratio of amyloid-beta 42 to amyloid-beta 40 over 20 blood samples per patient, the researchers could classify people accurately as amyloid-positive or amyloid-negative about 89 percent of the time. At any single time point, the average accuracy of testing was about 86%. Researchers at Washington University are also developing a blood-based test for tau. If successful, the use of both blood tests could provide an even better idea of which patients are at risk — much as cholesterol measurement is used as a marker for heart disease risk.

 

But PET scans and these new blood tests are not the only diagnostic strategies in use or in development to try to diagnose Alzheimer’s disease or the high risk of developing the condition at an early stage. In our next post, we’ll take a brief look at the field of Alzheimer’s diagnostics overall, and discuss where we see the field moving.