Dementia: we shouldn’t expect miracles from drug cures

The media do love to run reports about wonder drugs.  The latest is aducanumab,  which is being widely reported as a breakthrough in the treatment of Alzheimer’s disease.  The Telegraph   hails a ‘new drug that halts mental decline’.  The Mail headline asks:  Could this be the end of Alzheimer’s?  Revolutionary drug ‘may stop the disease from ever developing.’  For those with access, the actual report of the trial is in Nature.

There are several reasons why this is over-hyped, and it’s not just that this is based on a small sample from first stage trials.

  1.  Dementia is not a disease, but a syndrome; the symptoms of dementia are known to be the result of a variety of  different pathologies.
  2. It’s far from clear that Alzheimer’s is a single disease with a common cause.  It’s widely used as a residual category for dementias that have not been explained in other ways.
  3. It’s not clear how far the amyloid-β proteins that the drug is removing are actually responsible for dementia.  It’s a plausible hypothesis; but, as point 2 implies we should expect, there are some apparent cases of Alzheimer’s without amyloid-β plaques, and because the proteins (Aβ and tau) can build up for 15-20 years without symptoms emerging, the presence of the proteins does not mean that the person with a build up will suffer  dementia.
  4. It’s  not clear that whether, if the hypothesis is correct, the plaques impair cognition which might be relieved,  or cause permanent  damage.  This study claims, with few direct details,  that cognitive decline is slowed – but the comparison they make is not between drug receipt and placebo, but between those cases who had both received the drug and recovered better from plaques from those who received the drug without that effect.

Lastly, it ought to be noted that many people dropped out of the trial, at least 20 because of side effects.  The way that drug trials work – or should work – is that the tests should be able to refine the identification of those for whom the drug is appropriate, and those for whom it isn’t.  That takes time and good science, and hype and the search for miracle cures tends to get in the way of that.

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