As we age, our brains naturally shrink and our thought processes slow down. However, in Alzheimer’s disease, changes that occur in the brain are different to the changes seen in normal ageing.
More than one million people are expected to be living with Alzheimer’s or dementia in Britain by 2030, although it’s hoped that beginning early diagnosis and treatment could make it easier to tackle their symptoms. A new blood test, called plasma p-tau217, is currently set to revolutionise Alzheimer’s diagnoses, and is about to be used by some NHS patients as part of a study from the Essex Partnership University NHS Foundation Trust.
It can detect levels of amyloid and tau (two proteins associated with the disease) and researchers hope the test can “take us a step forward in revolutionising the way we diagnose dementia” if the trial is successful.
Here, professor of neurodegeneration at the University of Edinburgh Tara Spires-Jones answers your queries on symptoms, diagnosis and treatment.
What is Alzheimer’s disease?
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.
What’s the difference between dementia and Alzheimer’s?
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?
Alzheimer’s negatively impacts:
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.
Causes and risk factors of Alzheimer’s disease
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High blood pressure or diabetes
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.
Head injuries, a sedentary lifestyle, being overweight, and having high blood pressure or diabetes are associated with increased risk.
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 1-5 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 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.
However, soon a new blood test might be able to more accurately diagnose the condition. The test, called plasma p-tau217, has previously been shown to be effective in checking for two proteins in the brain which are linked to the disease.
It can detect levels of amyloid and tau, but researchers will now have to prove it can find them more quickly than existing, more invasive, treatments before any wider NHS rollout can go ahead. The study will recruit 1,100 people from diverse geographic, ethnic and economic backgrounds, alongside those living with other health conditions.
Essex Partnership University NHS Foundation Trust began recruitment a few weeks ago and 19 more UK centres are expected to take part. Experts hope to have the results within three years.
I think these type of bloods tests 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.
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.
They will be important because drugs like donanemab and lecanemab are treating specifically Alzheimer’s, and not other forms of dementia.
How common is early-onset Alzheimer’s?
Early-onset Alzheimer’s occurs in about one in 1,000 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 disease be prevented?
Exercising, keeping mentally and socially active, and getting your hearing loss treated are associated with reduced risk of dementia.
How is Alzheimer’s 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 breakthrough drugs donanemab and lecanemab, however those drugs have been rejected for use on the NHS by the National Institute for Health and Care Excellence (Nice). Nice insisted that the benefits were too small to justify the costs involved, though they have been approved by the medicines regulator, MHRA. It means they will only be available privately in the UK.
The performance of these drugs 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, 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.
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.
Tara Spires-Jones is professor of neurodegeneration and deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh.
As told to David Cox
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