Research emphasis on Alzheimer’s treatment shifts to pre-clinical stage

My friend was puzzled. “If we can’t treat Alzheimer’s disease, what’s behind the push for early diagnosis?”

It’s a good question and one that health care reporters should be able to answer as they report on this devastating illness.

A short response would go something like this:

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Evidence now indicates that biological processes underlying Alzheimer’s disease begin at least 10 to 15 years before symptoms associated with this illness become evident.

Every attempt to date to intervene in patients with mild or moderate Alzheimer’s disease has failed. That has led scientists to conclude that it’s too late to try to change the course of Alzheimer’s disease at the point at which fundamental disease processes have been under way for some time.

Instead, scientists hypothesize, treatment must begin much, much earlier – before any symptoms become apparent – if it stands any chance of being effective. (Sometimes this is called the pre-clinical stage of Alzheimer’s.)

But there’s a catch – a big one – to this approach. You don’t want to give potential treatments to people who will never develop Alzheimer’s, since all treatments have side effects and patients would presumably be taking these treatments for many, many years.

That means you have to have a pretty darned good idea of which patients are likely to develop Alzheimer’s and which are not before trying to intervene in the pre-clinical stage.

That’s where we are today. The search is on to identify “biomarkers” that can identify people who are very likely to develop Alzheimer’s and also to develop neuroimaging tools that can do the same. One day, scientists hope, they could draw blood from a patient and determine if he or she is headed on the path toward Alzheimer’s. Or, they could do a brain scan and see in real time the earliest biological markers of a disease process under way.

Then, the goal is to treat patients considered at very high risk of progressing to Alzheimer’s and see if intervening in this early, pre-clinical stage will have better results than intervening later in the disease process.

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It’s a logical approach, but there are important caveats.

The truth is there’s still considerable uncertainty about the biological mechanisms behind Alzheimer’s disease. Are the characteristic amyloid protein plaques and tau tangles observed in patients’ brains a cause of this illness – or a consequence? If they’re a cause, why are they found in the brains of older adults with intact cognition? Could something else be going on?

This is an alternative explanation for the failure of every single drug experiment to date that’s tried to halt Alzheimer’s in its tracks. Maybe trials that target amyloid and tau are pursuing the wrong target (or pursuing it in the wrong way), and that’s why they don’t work. It’s one reason why Ronald Petersen, M.D., Ph.D., head of the Alzheimer’s Disease Research Center at the Mayo Clinic, suggested in this interview with Nature that “we need to broaden our potential therapeutic targets.”

This year, of course, the big news has been the failure of much-watched drug trials for Alzheimer’s sponsored by Eli Lilly & Co. (its drug was called solanezumab) and Pfizer and Johnson & Johnson (their drug was called bapineuzumab). Both targeted people with mild to moderate Alzheimer’s and both failed to forestall cognitive decline or improve functional status in this population.

Also, there’s been news about the search for biomarkers for Alzheimer’s and how it’s progressing, such as these results from imaging studies announced in August. And there’s the expected launch of the first so-called “prevention” trials for Alzheimer’s set to begin later this year or next year. For the first time, these trials will test the hypothesis explained above by targeting people who are deemed at high risk for Alzheimer’s but who have not yet developed symptoms.

For a helpful description of where the field stands from one of its top scientists and a strong proponent of early diagnosis, see this TedMed video from Reisa Sperling, M.D., director of the Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital in Boston.

For an update on how scientists and drug companies are responding to recent disappointments in the search for Alzheimer’s treatments, see this piece in the September issue of Nature.

Finally, look at this series on Alzheimer’s published last year in The Atlanta Journal-Constitution to see how one publication has tried to educate its audience about this condition. (Here’s the lead story; look at the left-hand column for others.) Especially useful to reporters covering this topic is the Alzheimer’s timeline that the paper created, although that needs to be updated with information about the new national Alzheimer’s plan and disappointing drug trial results.

UPDATE: For an interesting radio interview on this topic, tune in to this piece that aired last week on Boston’s public radio station, WBUR. The journalist interviewed, Stephen Hall, teaches at Columbia University’s School of Journalism and recently authored an in-depth story, “The Dementia Plague” for Technology Review.

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