Alzheimer's Disease: Separating Hope from Hype

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Alzheimer's Disease: Separating Hope from Hype

August 23, 2024

News regarding Alzheimer's disease treatment is often a depressing affair. There have been a number of treatments in the last few years that have been shown to slow progress. However, with no cure in sight, Alzheimer's remains a chronic condition that is occurring in the population at an ever-increasing rate.

Prospects are often bleak, and for every positive article published regarding potential treatment, ten more are published of yet another lifestyle or medical factor that may increase the risk of dementia and Alzheimer's disease. Despite this, there remains hope for new treatments as more and more people see family and friends impacted by this devastating condition.

Still, it is important that media outlets and scientific communicators maintain a level of accuracy and responsibility in their reporting. In many instances, any hint of a new treatment results in phrases such as "cure" or the "beginning of the end" for Alzheimer's being thrown around lightly. This is both medically inaccurate and irresponsible reporting.

The difficulties in Alzheimer's drug development

Though new medications have been developed recently, with more in the pipeline, expectations and the resultant reporting must be tempered. For example, in an 18-month study, lecanemab was shown to reduce the rate of cognitive decline by 27%. While this is an improvement, the European Medicines Agency (EMA) has rejected its marketing authorisation request. They cited the relatively small improvement in symptoms while noting the "frequent occurrence" of amyloid-related imaging abnormalities, a side effect involving swelling and potential bleeding in the brain for the rejection of the application.

The decision by the EMA has come under fire by activists and disease advocates. This situation is representative of the current state of Alzheimer's treatment. A similar reaction was observed last year when the US Food and Drug Administration (FDA) decided to delay its decision on donanemab, waiting on further evidence. The drug had shown a 35% reduction in symptoms over an 18-month period, and so, in the media, was heralded as a success. The side effects of the medication, however, became an afterthought following the hype of a long-awaited new medication. According to interviews at the time, Dr Timothy Daly, a dementia researcher with Sorbonne University in Paris warned that the benefits of the drugs have proven harder to quantify than their potential harms.

Developing effective drugs for Alzheimer's disease has proven to be a notable challenge. For years, the majority of novel drug candidates have focused on the amyloid hypothesis, in which the accumulation of amyloid plaques within the brain causes disruption and damage to the neurons, eventually leading to disease symptoms. There is ample evidence to back this hypothesis, with mutations in genes such as APOE-4 and APP - both of which cause faster accumulation of amyloid plaques - resulting in early-onset Alzheimer's disease. However, while primary research in animal models yielded positive results, the resultant medications often showed limited efficacy. The genetic mutations that these medications were developed to target constitute a condition called familial Alzheimer's disease, these individuals represent less than five percent of all cases.

The resultant losses of the trial and error of researching Alzheimer's medications have resulted in pharmaceutical companies such as Pfizer dropping out of the field completely. The reality is that Alzheimer's disease is far more complex than just an accumulation of amyloid plaques.

The amyloid hypothesis has itself been called into question in recent years. In 2022, allegations were made that much of the original research that laid the groundwork for future amyloid studies was potentially fraudulent. Investigations took place that revealed that many images used in the research appeared doctored, and were likely spliced together from several experiments to better fit the hypothesis. Though many studies and drug developments continue based on the hypothesis, such allegations have resulted in diminished trust in scientific communication.

Modern theories have expanded into other research areas, highlighting the roles played by tauopathy (caused by the accumulation of neurofibrillary tangles), chronic inflammation, and even simply being an inevitability of living much longer lives. Often, approved treatments only show a marginal improvement in symptoms.

GLP-1 agonists may pave the way for future research

In more positive news, recent phase 2b trials have shown that liraglutide, a GLP-1 agonist used in the treatment of diabetes, has been shown to reduce shrinking in the parts of the brain that control memory, learning, language and decision-making by nearly 50% compared to placebo. Novo Nordisk's semaglutide is similarly being trialled for its capacity to slow Alzheimer's disease progression.

Though the mechanism by which GLP-1 agonists reduce the rate of Alzheimer's development is currently unknown, further research is already underway. Proposed theories suggest that a reduction in insulin resistance and inflammation may play a role.

The rebranding of currently used medications has advantages. Foremost, the safety profile is already well established. Particularly in the case of GLP-1 agonists, the demand is already skyrocketing, with companies now expanding production facilities to keep up with this demand. Should any of these medications also receive an indication for Alzheimer's, the demand will increase further, incentivising pharmaceutical companies to produce them.

Given that there are predictions that 10% of the US population could be taking some form of GLP-1 agonist by 2030, this could mean a fairly large degree of passive protection against the onset of Alzheimer's among the population.

The ever-evolving world of Alzheimer's disease risk factors

Additional risk factors, protective activities and lifestyle changes are studied and reported frequently. This presents a potential minefield for news outlets and scientific communicators. In truth, our understanding of the disease is limited.

There is a risk of the perception of almost anything being a potential causal factor, leading to messaging often being confusing. Red meat is a key example of this. Recent evidence indicates that even a small serving of processed red meat increases the risk of developing dementia. Other studies directly contradict this and suggest that low meat consumption is also associated with Alzheimer's disease risk.

Vaccines form another area of contention, and notably, one ripe for spreading misinformation. A recent study suggests that COVID-19 vaccination was itself associated with an increased risk of Alzheimer's development. This comes in the wake of numerous studies that indicate that contracting COVID-19 may be responsible for elevated incidence rates of Alzheimer's. Notably, and of the utmost importance to highlight, the odds ratio increase in Alzheimer's was higher after contracting COVID-19 than for those who received the vaccination.

Numerous other issues such as a lack of social contact, a notable increase in stressful circumstances and a lack of physical exercise during pandemic lockdowns are also cited as playing a role. There may also have been a degree of selection bias during the trials implicating vaccination as a risk factor for Alzheimer's. The individuals that are more open to receiving vaccines may be those that are already deemed to be part of at-risk populations and so, more prone to the development of Alzheimer's disease due to a number of potential medical issues.

Recently, a vaccine against shingles was found to play a role in protecting against Alzheimer's disease. Curiously, the protective effect was only observed in a live vaccine that has now been removed from the schedule of many countries in favour of a recombinant vaccine. The herpes virus itself is known to have an association with dementia risk, as do many other infectious diseases - underlining the importance of vaccination not just for the immediate risk of the diseases they prevent, but for lifelong health.

The list of risk factors is endless. A select few include: diabetes, obesity, depression, age, genetics, hearing loss, smoking, alcohol, a lack of physical activity, and even the air that we breathe. With all these risks in mind, it is important not to worry too much. Stress has also been shown to exacerbate the risk of Alzheimer's disease.

Contrasting the seemingly endless number of risk factors, some simple lifestyle factors can help to slow or stave off the development of Alzheimer's. A recent study has shown that a predominantly whole-food-based vegan diet, regular exercise and strength training, and stress management practices can help slow the disease's progression.

Effective communication amidst scientific uncertainty

With the impact Alzheimer's disease has on individuals, their families and friends, it is normal to want to look for hopeful news, something that can slow progress, or even halt the disease. I have had relatives diagnosed with Alzheimer's disease and vascular dementia. Watching their memories fade is a truly heartbreaking experience. It is natural to want to find hopeful news in this situation. But false hope of a potential cure where none exists is of no benefit to anyone.

With no cure in sight, effective communication must stick to the facts. Some people will still be diagnosed with Alzheimer's disease regardless of any risk factors being present. In many cases where genetic issues exist, this may occur tragically early. However, there are lifestyle factors that can mitigate risk, and even slow the progression of the disease. A healthy diet and a minimal amount of processed food, regular exercise, and a good night's sleep are all important - as they are in the case of most diseases. Vaccination presents less of a risk when contrasted against the disease itself, and so, is another important factor.

According to Alzheimer's Disease International, more than 55 million people worldwide lived with dementia in 2020. Projections indicate that this number will almost double every 20 years, reaching 78 million in 2030 and 139 million in 2050. With an ever-ageing population across most of the world, Alzheimer's is set to become one of the most disruptive health concerns we face. The disease already causes a significant economic and social burden. As more individuals potentially end their careers and drop out of the workforce to care for elderly relatives, this issue will be brought to the forefront of public attention.

As scientific communicators, our role is to underline the importance of advocacy and research. We must prepare for disease rates to increase, and with it, an ever-greater impact on the economy and our lives. Maintaining a straightforward and truthful message, despite the intricacies and complexities of Alzheimer's disease, is essential to its understanding, and our progression in treating the condition.

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TAGS: Health

POSTED BY: Nick Parry

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