12 August 2021

Race Towards a Cure: Alzheimer’s and an Ageing Population

Written by Claire Bonneau

Over the past decade, the average life expectancy has dramatically increased around the world. In the 1950s, the average global life expectancy was estimated to be 47 years old — a number that our modern society has increased with the aid of modern medical technology and increased access to resources like food and clean water. As of 2020, the global average life expectancy is now 73 years, with the trend expected to continue to grow to 77 years by the year 2050 (1).

And while these advances in life expectancy are having a positive impact on the lives of people around the world, it has also caused an increase in the diagnosis rate of age-related neurological disorders like Alzheimer’s disease. Now considered one of the top ten leading causes of death around the world, Alzheimer’s disease has had a profound impact on the health and quality of life of the ageing population. 

Despite being identified over 115 years ago, we still have no cure for Alzheimer’s. Even more frighteningly, it seems that our progress on developing medications and treatments for Alzheimer’s disease has seemingly hit a standstill. While our top researchers have been able to tackle and create an effective vaccine against COVID-19 in only a matter of months, the last FDA-approved drug for Alzheimer’s disease was greenlit in 2003, over eighteen years ago (2). It seems that while we are making strides in other areas of modern medicine, the list of failed treatments of Alzheimer’s disease is growing larger by the day.

So, as our global society continues to trend towards increased life expectancy, we are quickly realising that Alzheimer’s disease is a slow-motion time bomb that we need to act on sooner rather than later.

So, how big is the problem exactly?

Alzheimer’s disease is a neurological condition that results in the progressive destruction of healthy functioning brain tissue (3). Over time, a person with this condition will experience memory loss, difficulty problem solving and eventually will lose the ability to perform basic self-care activities like feeding themselves or brushing their teeth.

It is estimated that over 5.8 million American adults over the age of 65 have been diagnosed with Alzheimer’s disease, with the number increasing every year to date (4). For most people with this condition, the onset of symptoms appears in their early to mid 60’s (5). This is the most common age of disease onset, and people in this age range are considered to have late-onset Alzheimer's. It is possible for people as young as 20-30 to develop symptoms of Alzheimer's, though this form of the early-onset disease is significantly rarer.

Alzheimer’s Fact Sheet:

  • It is estimated that 1 in 5 people is at risk of developing Alzheimer’s disease in their lifetime.

  • The United Nations estimates that over 50 million people worldwide are living with Alzheimer’s dementia — a number that is larger than the entire population of Columbia (6).

  • The number of people living with Alzheimer’s dementia or other related cognitive impairments is estimated to triple by the year 2050 (7).

  • Up to 1 in 3 younger people with early-onset Alzheimer’s disease have an atypical form of the disease, while only 1 in 20 people with late-onset Alzheimer’s disease have an atypical form (8).

  • New research has shown that Alzheimer’s disease is in the top three causes of death amongst seniors, following heart disease and cancer (3).

  • Alzheimer’s care comes with a significant cost, with the global cost of the disease reaching over $604 billion dollars in 2010, which is equivalent to 1% of the global domestic product (GDP) (9). On average, people living with Alzheimer's disease cost American’s over $200 billion dollars in caregiving and lost productivity costs. Without intervention, it is estimated that the cost of care for Alzheimer’s patients will exceed 1 trillion dollars by the year 2050.

  • It is estimated that 75% of all people who act as caregivers for people with Alzheimer’s are family members or friends (10). The heavy burden of care has placed extra financial and emotional stress on family units, which has long-lasting impacts on those providing the care.

So, if Alzheimer’s disease is as serious of a condition as it appears, why have we not found a cure yet?

Let’s follow the money — the desperate need for more funded research

The true problem with Alzheimer’s research is that the scale of the money and time invested has never matched the size of the problem. Because of this, Alzheimer’s research is profoundly underfunded, which has resulted in minimal to no advancements in treatments for the disease in almost two decades.

There appears to be a severe discrepancy in the funds available for finding a cure for Alzheimer’s disease when compared to other less fatal conditions. In the United States, the federal government invests up to twelve times more resources into cancer research than Alzheimer's research, despite the fact that the yearly mortality rate from Alzheimer’s is higher than all cases of breast cancer and prostate cancer combined (11).

Similarly, the American federal government spends an average of $4 billion dollars annually on supporting cardiovascular research and treatments — and this investment has proven to be successful. From 1999 to 2011, the number of patients aged 65 or older who were hospitalised due to a heart attack was reduced by 40% (12). In the same time frame, only 1% of that budget is used to fund research to find the cure for Alzheimer's. As the number of people who are diagnosed with Alzheimer’s is continuing to rise, we have made no major strides in disease-modifying medications or cures.

While it seems incredibly clear that we need to increase our global investment into finding treatments for Alzheimer’s, social factors such as ageism may be getting in the way of any medical breakthroughs. The myth that elderly people are the only people who are affected by this disease is limiting the available resources for finding a cure to treatment. And while this disease does commonly impact seniors, it is important to note that 5-10% of people with Alzheimer’s are under the age of 65 years old (11). Additionally, the burden of care for patients with this condition has a massive impact on the entire family unit and has been connected to increased anxiety, depression, and exhaustion in the people acting as the primary caregivers.

The human brain is complex - and Alzheimer’s disease is the most complex disease of the brain

Another reason for the slow development of Alzheimer’s treatments is the lack of information we currently have about the true cause of the disease. Some of the most common theories include:

  • The Misfolded Proteins Theory — The most time-honoured theory involves a malfunction of the proteins within the brain (13). Believed to be caused by misfolding proteins turning to clumps of unusable cells, this theory suggests that the loss of functioning cells in the brain is what causes the progressive loss of memory and cognitive ability. It was originally believed that the beta-amyloid protein was responsible for the misfolding, but recently another contributor, the tau protein, has been added to this theory.

  • The Neuroinflammation Theory — In this newer theory, it is believed that damage to the cells of the brain may be caused by chronic inflammation (14). Possibly caused by the release of a toxic substance released by immune cells in the brain called microglia, more research is being done into medications designed to target these specific cells.

  • Other Lesser Known Theories — There are other theories that are often included in the possible explanations of more common theories. Research has shown that Alzheimer’s disease may impact synaptic junctions in the brain, the locations between neurons that pass information from one place to another through the use of neurotransmitter chemicals. Impairment of the synaptic junctions could explain why people with Alzheimer’s disease have difficulty with performing physical tasks as the disease progresses. Additionally, it is believed that the mitochondria (the energy source of every cell) could also be involved in the development of Alzheimer’s disease.

As more research is being done into finding the cause of Alzheimer’s disease, we are starting to shift our focus on which areas we design our treatments to target. In 2008, over 27% of all Alzheimer’s research was focused on the amyloid plaques, as it was believed that the misfolding protein theory was the most likely cause of the disease (12).

Since then, more advances in medical technologies have caused us to diversify our research to more areas. In 2017, only 17% of resources were spent on research for amyloid plaques, and areas such as genetic factors, brain synapse circuits, and neuroinflammation have all increased.

The difficult path ahead for finding the cure

Like all serious diseases, the search for the cure for Alzheimer’s disease is incredibly complex and multi-faceted. Unfortunately, in recent years, all possible theories for the cause of Alzheimer’s have only led to failed drug trials and no new advances in modern treatment options. As researchers continue to try to push for future advancements in treatments, some common themes emerge that get in the way of continued progress. 

#1 — Controversial drug approvals

One of the more controversial developments in Alzheimer’s treatment has been the rapid and unorthodox approval of a medication called Aducanumab. During clinical trials on patients with profound disease, it was found that one group may have experienced a positive outcome of removing some of the built-up amyloid plaques in the participants’ brains. Instead of conducting the normal path of approval, this medication was pushed through the FDA approval period at a rapid speed, despite the limited information about the true success rates and long term effectiveness of this medication. This is a perfect example of the importance of the need for time and resources to ensure that the possible treatment options are effective in treating this condition.

#2 — Drug trial ethics

It is believed that Alzheimer’s is a chronic disease that is present up to 20-30 years before developing symptoms. Currently, we are unable to detect the disease without significant damage already having been done to the brain, resulting in a diagnosis of this condition being late into the progress of the disease. Because we do not have the ability to diagnose people with Alzheimer’s years in advance from the onset of symptoms, we would need to consider the ethics of giving a potentially harmful drug to someone who may or may not get a disease in the first place.

#3 — Long and expensive drug trials

Unlike medications like antibiotics that can prove to be effective in a matter of days, it takes years for Alzheimer drug trials to prove if they are effective. This prolonged period of drug testing time is expensive, difficult to upkeep, and dramatically slows down the process of creating new and possibly more effective drugs.

Investment in Alzheimer's research is about more than extending life

One of the most important takeaways from this article is that there is an urgent need for increased and aggressive research into the cause, diagnosis, and possible treatments for Alzheimer's disease. As our population continues to age and live longer every year, the need to stay on top of neurodegenerative diseases like Alzheimer’s disease is only going to increase every year.

In a recent study, it was suggested that up to 40% of Alzheimer’s disease cases could be prevented through better management of lifestyle and health practices (15). Improving our knowledge of the disease and offering better treatment options is not only the best way to give people more time with their loved ones, but it also allows for the people diagnosed with Alzheimer’s disease to have a better quality of life throughout their diagnosis.

Continual research, investment in drug trials, and more accessible education about the disease are our best options to keep pushing forward to finding a cure for Alzheimer’s. With new treatments hopefully on the horizon, increasing the awareness of this disease and encouraging people to participate in clinical trials will greatly help our researchers begin to make the breakthroughs we need to finally cure Alzheimer’s disease.

The introduction of the Decade of Healthy Ageing

Looking to make global strides in education and awareness about healthy ageing, the United Nations announced the Decade of Healthy Ageing project (2021-2030). Designed to be a global collaborative initiative, this project will foster advanced care and resource allocation to their four action areas (16):

  • Age-Friendly Environments — Social determinants of health such as physical, emotional, and social supports are essential for healthy ageing. The creation of more age-friendly environments will allow for increased participation of our seniors in our modern society.

  • Combating Ageism — Ageism is, unfortunately, a systemic part of our medical and social structure. Finding ways to educate people about harmful ageist stereotypes and prejudices is essential for reducing discrimination against our older population.

  • Integrated Care — Everyone deserves non-judgmental and non-discriminatory care. This project aims to provide high-quality preventative, rehabilitative, and curative care to all seniors.

  • Long-Term Care — Access to good-quality end of life care is a human right. This area aims to promote access to rehabilitative technologies and treatments to both seniors and their caregivers to improve everyone’s quality of life.

With these initiatives in place, the UN is hoping to reduce systemic ageism and better encourage continual research and support to diseases that primarily impact the elderly such as Alzheimer’s disease.

Sources:
  1. Life Expectancy from Our World in Data: https://ourworldindata.org/life-expectancy

  2. Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research: https://www.mdpi.com/2227-9059/7/4/97

  3. Alzheimer’s Disease Fact Sheet from the National Institute on Ageing: https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

  4. 2020 Alzheimer’s Disease Facts and Figures from the Alzheimer’s Association: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12068

  5. What are the signs of Alzheimer’s disease? from the National Institute on Ageing: https://www.nia.nih.gov/health/what-are-signs-alzheimers-disease

  6. Alzheimer’s: Facts, Figures, and Stats from BrightFocus Foundation: https://www.brightfocus.org/alzheimers/article/alzheimers-disease-facts-figures

  7. Addressing Alzheimer’s disease and related dementias to realise the promise of the UN’s ‘Decade of Healthy Ageing’ from VoxEU: https://voxeu.org/article/alzheimer-s-and-un-s-decade-healthy-ageing

  8. What causes young-onset dementia? from the Alzheimer’s Society: https://www.alzheimers.org.uk/about-dementia/types-dementia/what-causes-young-onset-dementia

  9. The Cost of Dementia from the Institute of Neurodegenerative Diseases: https://ind.ucsf.edu/supporting-our-work/cost-dementia

  10. Family caregivers of people with dementia from NCBI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181916/

  11. Alzheimer’s Facts and Figures Report from the Alzheimer’s Association: https://www.alz.org/alzheimers-dementia/facts-figures

  12. The Alzheimer’s gamble: NIH tries to turn billions in new funding into treatment for deadly brain disease from AAAS: https://www.sciencemag.org/news/2018/08/alzheimer-s-gamble-nih-tries-turn-billions-new-funding-treatment-deadly-brain-disease

  13. Alzheimer’s disease - Symptoms and Causes from the Mayo Clinic: https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447

  14. Inflammation as a central mechanism in Alzheimer's disease from NCBI: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214864/

  15. The Lancet: 40% of dementia cases could be prevented or delayed by targeting 12 risk factors throughout life from the Alzheimer’s Association: https://www.alzheimers.org.uk/news/2020-07-30/lancet-40-dementia-cases-could-be-prevented-or-delayed-targeting-12-risk-factors

  16. UN Decade of Healthy Ageing from the World Health Organization: https://www.who.int/initiatives/decade-of-healthy-ageing

The author, Claire Bonneau, is a medical writer and certified trauma operating room nurse.

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