Over the years, there have been many efforts to identify in-vitro diagnostics, in cerebral spinal fluid (CSF) or blood, for Alzheimer’s disease (AD). While there have been many studies, nothing has become used in routing clinical practice. Is this a function of the biomarker discovery process, or is it the result of other reasons?
A study was done to look at what clinicians and researchers thought about these issues. Some of the results may be surprising.
First the high-level conclusions:
- Concentrate short term on moving current CSF assays (abeta, tau) to blood, rather than new biomarkers.
- Focus new biomarker efforts on the early part of the disease onset, including identification of latent disease and transformation from mild cognitive impairment.
- Deemphasize efforts on broad screening, and ruling out (rather than ruling in) AD.
As to specific survey results –
- 60% of AD patients diagnosed clinically
- Another 20% diagnosed with the aid of imaging
- Only 5% more get diagnosed with the aid of current (CSF) biomarkers
- But only 30% of doctors surveyed use current biomarkers
- Of all the patients with suspected AD, 15% end up with an indeterminate diagnosis
One of the potential implications of these findings is that if all physicians involved in diagnosing AD – instead of just 30% – used current CSF biomarkers (abeta and tau), then virtually all patients with suspected AD could be differentially diagnosed.
Does this mean that better proof is needed, or that different guidelines should be used? One other answer to the question is based on CSF. 9 out of 10 MDs, of the 70% who don’t use CSF biomarkers, would use them if in blood. Even 1/3 of the 30% who currently use CSF biomarkers believe that blood-based assays, comparable to today’s abeta and tau CSF tests, would be used more.
However, there are still clinical and market risks for blood tests, due to new imaging capabilities. Eli Lilly and GE have received FDA clearance for PET scan injectable contrast agents, Amyvid and Vizamyl respectively. These agents help image beta-amyloid plaques in the brains of living patients. As imaging is used as an adjunct 4 times more often than in-vitro biomarkers for AD diagnosis, this advancement may both reduce the need for biomarkers, as well as decrease the percent of patients with an indeterminate diagnosis.
So, in addition to trying to push just the current assays into blood, what other strong interests are there in AD “diagnostics” that might be fulfilled with in-vitro diagnostic tests?
The survey revealed potentially surprising results as seen in the figure below. Better tests for early diagnosis of AD or latent AD, and transformation from mild cognitive impairment were wanted. However, there was little interest for screening assays or ruling out potential AD patients.