A breakthrough new drug to treat brain disease is always welcome news. Last summer, the performance of the drugs donanemab and lecanemab in clinical trials was a landmark moment for scientists because it was proof of principle that we can slow Alzheimer’s disease by between 27 and 35 per cent. That’s the first time this has been demonstrated.
However, with a decision on the approval of the drugs in the UK from the Medicines and Healthcare products Regulatory Agency (MHRA) expected soon, there is an important caveat.
Firstly, it is not yet clear whether the effects will be noticeable to people living with Alzheimer’s and their families. In the study report, the researchers describe it as modest, which is a concern given how expensive they are and the potential for dangerous side effects.
Furthermore, the drugs are able to clear amyloid from the brain, as they’re designed to do, but people won’t get better when taking them. Rather, they get worse more slowly.
What is Alzheimer’s and how is it different from dementia?
Alzheimer’s is a disease that occurs in your brain. It’s characterised by brain shrinkage, which is caused by brain cells progressively dying, and the accumulation of plaques and tangles, the two major hallmarks or pathologies of Alzheimer’s.
It was first described by the German psychiatrist and pathologist Alois Alzheimer back in 1906.
To be clear, Alzheimer’s is a brain disease which causes dementia. Dementia is not a disease per se, it’s a set of symptoms which can be caused by lots of different diseases. Alzheimer’s is the most common cause, but you can have dementia symptoms because of other diseases such as vascular dementia or frontotemporal dementia, for example.
What are the symptoms of Alzheimer’s disease?
In the very early stages of Alzheimer’s disease, people start having trouble with cognition, such as memory and spatial memory. This can be remembering where you put things or what happened earlier in the day, but as the disease progresses, the symptoms become more severe, and people’s behaviour and personality can change. There can be aggression and disinhibition such as saying inappropriate things that you would usually filter. That’s because the frontal cortex in your brain, which controls those impulses, is dying.
It manifests in lots of different ways, and patients can have symptoms that affect everything in their life, including movement and the inability to recognise loved ones.
In the end stages, so much of the brain has died that people are just reduced to their beds. They can’t speak, they can’t move. It’s very debilitating.
What age do people start to show the signs of Alzheimer’s?
It is most common in people over 65. Around one in 11 people over the age of 65 have dementia in the UK, according to the NHS numbers, which is pretty shocking.
Alzheimer’s Research UK estimates that one in two people will be affected by dementia, either by caring for someone with the condition, developing it ourselves, or both.
How is Alzheimer’s diagnosed?
People concerned about how their memory or cognition is changing with age can go to their GP and they may be referred to a specialist memory clinic where they’ll take lots of tests. It begins with easy questions such as, “What year is it?” “Who’s the Prime Minister?” “What floor are you on?” The GP then assesses whether their cognition is intact.
An MRI scan can also be used to look at whether the brain has a characteristic pattern of shrinkage that might indicate early Alzheimer’s. There are more sophisticated tests like looking in cerebrospinal fluid or a PET scan, which directly visualise those changes happening in your brain, but those are usually only used for research studies.
There are emerging blood tests which detect changes in the levels of proteins like amyloid and tau that clump in the brain. But they’re not perfect yet, in part because some people have pathology but don’t have any symptoms because their brains are very resilient and can cope with it. Currently, they’re not being used as diagnostics because it is not possible based on these tests to say for sure that a person has Alzheimer’s. Researchers are working to improve these tests and, at some point, I think they will become available to the public alongside the memory clinic assessment as part of determining whether people are in the early stage of Alzheimer’s disease.
They will be important because drugs like donanemab and lecanemab are treating specifically Alzheimer’s, and not other forms of dementia.
Is Alzheimer’s genetic?
There are very, very rare familial forms of Alzheimer’s that are inherited from your parents, but they’re generally early-onset and tend to run in the family. Only around 1 to 5 per cent of people with Alzheimer’s have one of these genetic mutations.
But a lot of patients have what we call polymorphisms. These aren’t genes which cause the disease, but they increase your risk. For example, there’s one called APOE4 which substantially increases your risk. If you inherit two copies of APOE4, your risk is 10 times higher than if you didn’t inherit any copies at all.
What are the causes of Alzheimer’s disease, and can it be prevented?
There are three things that contribute to your risk – as well as genes, there is age and lifestyle. So the older you are, the more likely you are to develop dementia, while estimates suggest that 35 to 40 per cent of Alzheimer’s cases could have been prevented by lifestyle modifications.
Exercising, keeping mentally and socially active, and getting your hearing loss treated are associated with reduced risk of dementia, while head injuries, a sedentary lifestyle, being overweight, and having high blood pressure or diabetes are associated with increased risk.
How common is early-onset Alzheimer’s?
Early-onset Alzheimer’s occurs in about one in 1000 people aged 30 to 64. The changes in the brain are almost exactly the same as in people who develop Alzheimer’s later in life, they just happen earlier and more aggressively. It is these cases which are more likely to have a genetic component.
Can Alzheimer’s be treated?
There are several approved treatments for patients with early to mid-stage Alzheimer’s such as donepezil, galantamine and rivastigmine. These treatments mostly boost the levels of a brain chemical called acetylcholine. These treatments aid your symptoms and help you think a little bit better in the moment, but they don’t stop that underlying brain cell death.
And then there’s donanemab and lecanemab, but those drugs aren’t approved in the UK yet.
Is there a cure for Alzheimer’s?
Unfortunately there isn’t a cure at the moment, but I’m very hopeful that we will have a combination of preventative and disease-modifying treatments in future. I don’t know if we’ll be able to cure everyone, however I’m hoping we can prevent many cases, and in others, at least substantially slow down the disease so it’s not something that defines you and steals your memories and personality.
There are still safety questions about donanemab and lecanemab – side effects like brain bleeds or swelling occurred in some people in the trials – and there are also reports of brain shrinkage. Administering these drugs and monitoring for side effects requires multiple doctor’s visits and scans.
I’m optimistic that in the future we will have combinations of treatments – for example, drugs which have a neuroprotective effect on the brain, as well as those that remove plaques and tangles. If we can catch Alzheimer’s really early with new diagnostics like blood tests, then hopefully future treatments will be able to stop progression and turn Alzheimer’s into a chronic but manageable disease which people can live with. - As told to David Cox
- Tara Spires-Jones is professor of neurodegeneration and deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh. She is also a group leader in the UK Dementia Research Institute.
