Preventing Alzheimer’s disease: are we there yet?

Preventing Alzheimer’s disease: are we there yet?

During his speech at the G8 Summit in 2013, former Prime Minister David Cameron branded dementia ‘one of the greatest enemies of humanity’ and pledged Britain to lead the global fight to find a cure for this disease by 2025.

Although significant progress has been made since, dementia costs the UK economy £26.3 billion a year and is now the leading cause of death in England and Wales, overtaking heart disease for the first time.

Dementia is a term used to describe a constellation of symptoms which often include memory loss and difficulties with language, thinking or problem-solving. Dementia develops when diseases such as Alzheimer’s damage the brain.

In Alzheimer’s disease, abnormal clusters of protein called amyloid plaques and neurofibrillary tangles form in the brain, causing death of nerve cells and subsequently cognitive deterioration.

The most common cause

Although Alzheimer’s disease is the most common cause of dementia, due to its progressive nature, it is often not diagnosed until years after it has started to ravage the brain. In the early stages, memory loss and other cognitive symptoms are mild. Consequently, in most cases by the time a diagnosis is warranted, irreversible pathological damage has already taken place, making it very difficult to halt further cognitive deterioration.

However, in recent years, researchers across the globe have joined forces in an attempt to diagnose Alzheimer’s disease at the earliest possible stage in the disease course.

Simultaneously, pharmaceutical companies are investing billions of dollars every year in their hunt to develop the first miracle drug; a drug that will tackle the underlying disease process in Alzheimer’s, rather than just treat its symptoms.

Combined, these efforts could mean that the neurodegenerative disease is detected and treated early on, potentially saving millions of people from progressing to dementia. So, how close are we to making this dream come true?

The track record of drug development in this area has been disappointing to date. However, the clinical trial failures of several promising drugs has really progressed understanding of what is needed.

It has become clearer that the disease needs to be treated, and therefore diagnosed, earlier, and that drugs need to be given in sufficient dosage to have a beneficial effect.

In September of 2016, trials of a new monoclonal antibody drug – Aducanumab –made headlines after early results showed it to considerably reduce amyloid in the brain – one of the two biomarkers associated with Alzheimer’s disease.

Patients with early Alzheimer’s disease who took the higher dose of Aducanumab for 54 weeks showed not only a significant reduction of amyloid on PET scans, but also less cognitive deterioration, compared to those on placebo.

Trials encouraging

Principle Investigator and Consultant Neurologist Dr Richard Perry (Imperial Memory Unit, Charing Cross Hospital) explains “The results from the Aducanamuab trial are truly encouraging; although it is early days, it is exciting that we are able to modify the underlying pathology but even more so that this translates into improved cognition for patients in their everyday lives. Now we have to see if these results can be replicated in larger numbers of people, over longer periods of time”.

Such positive results have now fuelled a worldwide quest to develop the first ever preventative treatment in Alzheimer’s disease; a concept that could quite simply eradicate Alzheimer’s disease altogether. The aim of preventative research is to capture individuals who are at increased risk of developing Alzheimer’s disease and treat them before the onset of symptoms. This can be facilitated by genetic testing; individuals who carry the APOE4 genotype are significantly more likely to develop Alzheimer’s disease than those who do not.

New study

A new study, named the Generation study, aims to investigate the effectiveness of two different types of drugs targeting amyloid in individuals who are at increased risk of developing Alzheimer’s disease due to their genetic make-up, however have not yet exhibited any cognitive symptoms.

Dr Perry explains “We are thrilled to be involved in this type of research. Halting or slowing the disease process before people develop symptoms is clearly the way to tackle this disease in the future. It is exciting to be able to offer this type of research to our patients, especially those who may be anxious about their risk of inheriting the disease. Certainly, the Generation study could play a crucial role in our national mission to cure Alzheimer’s disease by 2025”.

If you are interested in learning more about Alzheimer’s disease research or would like to take part, please call 0203 313 5515 or visit www.imperial.nhs.uk/research/research-facilities/imperial-memory-unit