Brain Scan Diagnostics for early detection of Alzheimer’s --- a good idea?

Posted: Jul. 26, 2010

There is debate about this.  A panel of leading Alzheimer’s researchers has recommended new guidelines for earlier diagnosis of Alzheimer’s Disease (AD), including the use of brain imaging.  While most commentators have hailed this news, a few have raised concerns. One of the clearer expositions of this was a Forbes online blog by Robert Langreth on July 15 entitled “A Scary Idea: Pre-emptive Brain Scans for Alzheimer’s.”

Langreth hypothesizes this diagnostic report:
“You feel fine and have no symptoms, but your brain is slowly rotting away. And there is nothing we can do about it.” Maybe he should have added “now”.

What is behind all this, and is this proposal really useful for patients and research?

First, what did the panel of experts say? Let’s be clear: the panel does not recommend these tests for patients clinically. They are recommended for research-based clinical trials only, not for treatment of patients generally. A big difference which much of the media has chosen to ignore in favor of the more sensational “know what you have before you can cure it” story.  The panel is recommending the use of brain scans and other biomarkers or physical indications of the presence of AD pathology in pre-symptomatic people for research into how AD pathology originates, progresses and ultimately how it can be stopped. Again, these measures are for research purposes only and have no immediate clinical application.

Ah, there’s the rub. It is so easy --- and wrong --- to hail a fundamental advance in research or ideas for new research as having immediate clinical benefits when there are none now. So, the net effect is to tarnish an excellent approach to useful research that will ultimately help to bring relief to patients and their families with sensational and exaggerated claims or suggested impact.  Hence Langreth’s concern, based on a mis-reading or non-reading of the actual recommendations of the panel.

There really is good news here. This kind of data from a wide array of individuals could dramatically accelerate the speed of development of effective therapies by giving scientists more reliable targets for therapeutic intervention.

For example, the reason that brain scanning or imaging is emerging as a potentially effective diagnostic technique has to do with a) the imaging technology itself, but more importantly b) better knowledge about what to look for.  And what to look for in pre-symptomatic  potential AD patients is not the sticky ‘”plaques” which have characterized the presence of the disease in the past, but the presence of collections of the protein Abeta in the brain. Researchers have thought for the last twenty five years that the little protein (peptide) Abeta was the “bad guy” in AD pathology. It turns out that that is true, but that the Abeta molecules need to be aggregated into clumps called “oligomers” before they are truly toxic to the neuronal synapses in the brain. This is a relatively new revelation, brought to the field and largely legitimized by research funded by Cure Alzheimer’s Fund (CAF). As early as 2006, the Oligomer Collaborative of CAF was being funded for innovative research into the presence, characteristics and functions of oligomers.  An article appeared in CAF’s 2007 Quarterly Report for the 4th quarter by Dr. Charles Glabe of the University of California, Irvine explaining what these oligomers are and why they are important. (link to: http://www.curealzfund.org/spotlights/targeting-amyloid-oligomers-in-alz...)

Having the right target and the right technology to see it is important, but not sufficient. Until we know more about how those oligomers affect the neural synapses, and how we can modulate or prevent their toxicity from interfering with healthy brain function,  we still can’t help the patient very much.  But given the ability to see those Abeta oligomers form and following what they do IS a significant contribution toward preventing and/or curing the disease.

This is another good example of a) the importance of focused research; b) the value of collaboration among leading scientists to understand the pathology of the disease as well as to develop and deploy technology that can take advantage of that knowledge,  c) the need to accelerate research into the most promising areas of investigation to prevent or interrupt the pathology before it becomes symptomatic; and d) the need to be clear about the benefits of these research-oriented procedures  which can lead to better clinical outcomes, but certainly not immediately.

So, are the new guidelines proposed by the panel a good thing? Yes, as a significant next step to accelerate research, and provide solid evidence of progress. But at the same time, we have to be very careful not to impute false clinical benefit to this development now --- that is a cruel abuse of the hope that all Alzheimer’s patients and their families and caregivers have that “a cure is around the corner”. The corner will only get closer with more resources committed to focused, strategic research that builds on this kind of work.