Promise of new medications yet to be tested

Dementia affects about half a million people in this country and the numbers are set to increase two to three-fold in the next few decades.

About two-thirds of dementia cases are due to Alzheimer’s Disease and so the personal and societal repercussions of a cure would be huge.

It is worth noting that until these medications came on the scene there had been no treatment proven to treat the condition, despite many decades of research. We do have medications that treat the symptoms, but not the underlying disease.

So, what do we know about these medications?

Well, they are all from the same class – that is, the way in which in which they work is fundamentally the same. They are known as monoclonal antibodies and are proteins which have been artificially created to act like antibodies in our body (and brain).

The role of antibodies is to neutralise foreign substances and in so doing, prevent the harm that these substances might cause.

The monoclonal antibodies that have been in the spotlight recently for Alzheimer’s Disease target amyloid, the accumulation of which in the brain is thought by many to be responsible for the symptoms of the condition.

There is controversy about this (isn’t there always!) but that’s a story for another day.

The antibodies “recognise” amyloid as a foreign substance, bind to it and clear it from the brain. This should be a good thing – less amyloid should mean less damage to the nerve cells which should mean less symptoms of memory loss and the like.

There are two of these medications available to patients in the USA already (aducanemab and lecanemab) but they are not yet available in Australia. This may change soon.

Positively, studies do show that their use does reduce brain amyloid load. The problem is whether the clinical effects are relevant i.e., is there a meaningful improvement in day-to-day cognition and function.

Both drugs, when given over 18 months, do slow cognitive decline (by 22 per cent and 27 per cent respectively) but what this means for the someone with dementia is hard to define.

There are many that welcome the treatment option despite this uncertainty – after all, at least it is something.

There are others that are less optimistic, however. The drugs are expensive and must be given as in infusion (so not user-friendly). Also, although they slow cognitive decline, they do not stop it or reverse it: there is still overall, a downward trajectory.

Additionally, there are specific concerns that the medications may accelerate shrinkage of the brain (whether this is clinically relevant is unclear) and in some people can cause swelling and bleeding in the brain.

The bleeding has been tied to at least three deaths in those treated with lecanemab.

There may be more benefit to be had from these medications if you start them earlier, and this is the subject of ongoing research.

It may also be that these early drugs are stepping stones to the development of similar agents where there is more benefit and less potential for harm.

Of course, it will always be an individual decision whether to try these medications – you may be happy to accept the potential for side effects, and your neighbour may not.

I suspect I will be having regular discussions about the pros and cons with my patients over the coming years.

Kailas Roberts is a psychogeriatrician and author of Mind your brain The Essential Australian Guide to Dementia now available at all good bookstores and online.
Visit yourbraininmind.com or uqp.com.au