In 1906 Alois Alzheimer described the case of Auguste D. to a group of fellow psychiatrists in Germany. Auguste, who was only in her 50s, had profound memory loss, unfounded suspicions about her family and other worsening psychological changes. At this time, it was generally thought that dementia was a normal part of aging and affected only the elderly. After Auguste’s death, Dr. Alzheimer carried out a post-mortem analysis of her brain and found dramatic shrinkage and abnormal deposits in and around nerve cells. Four years later, Emil Kraepelin, a German psychiatrist who worked with Dr. Alzheimer, first named this new mysterious condition “Alzheimer’s Disease” in the eighth edition of his book Psychiatrie.
Since then a plethora of research has been carried out and we now know that dementia is not in itself a defined disease. It is an umbrella term used to describe a multitude of symptoms. These symptoms can include memory loss, difficulties with thinking, perception, judgment, problem-solving or language, as well as changes in mood or behaviour. Essentially, it is our cognition that becomes affected, although it has been shown that often this can be accompanied by physical symptoms, too. Dementia is the result of damage to our brains, caused by diseases such as Alzheimer’s disease or multiple strokes. Alzheimer’s disease is the most common cause of dementia, although the exact mechanisms that cause Alzheimer’s remain unknown. Thus, it is not a surprise that to date no treatments that can halt or cure Alzheimer’s disease have been developed.
Sometimes people get lucky, and find a treatment for a disease by chance, like Alexander Fleming who accidentally discovered Penicillin in 1928, and saved the lives of millions of people. However, the chances of getting lucky are very small, and for over 100 years now researchers have been trying to find treatments for Alzheimer’s disease. Despite widespread efforts, they have remained unsuccessful. Why is this? To answer this question, let us think about what we would need to know to develop a treatment that can halt or reverse the progression of a disease that causes dementia.
The first thing that we would need to be able to do, is to have a test that allows us to give a definite diagnosis so that we know what it is that we want to cure. However, diseases that cause dementia such as Alzheimer’s disease can only be diagnosed after death. A post-mortem analysis of the brain is required to give a definite diagnosis of Alzheimer’s disease. In fact, approximately 20% of people are misdiagnosed. How can we expect to treat something we cannot even identify? In addition, it is likely that many neurodegenerative diseases start long before (approximately 20 years) symptoms become visible. This means we need to find biomarkers that will allow us to identify and diagnose a disease process early on. The earlier we can treat, the higher the chances of success.
Secondly, we need to bear in mind that there is a multitude of diseases that cause dementia. And even within those diseases, there are likely significant differences between individuals. We know this because there is such heterogeneity in disease presentation. Some people progress rapidly, others live for many years and changes only occur very slowly. Take for example Alzheimer’s disease, it is very likely that there are numerous subtypes of this dementia-causing disease. Therefore, we need to use stratification to develop personalised treatment approaches by identifying subtypes of the disease. In cancer research, this kind of approach has been very successful.
Once we have identified what the condition is that we want to cure, we have to study it in detail. This poses one of the key challenges to neuroscientists, as we cannot study the live human brain. We can only really examine it in detail, once someone has died. This means we do not know what the exact ongoing disease processes are when a person is still alive. Techniques such as magnetic resonance imaging allow us to get some idea of the areas that are involved in certain diseases, but they are by no means detailed enough to give us a true understanding of the underlying mechanisms. With improvements in technology, we will hopefully be able to create more sophisticated methods to study the live human brain in the future. Until this time, neuroscientists rely on animal and cellular models to study diseases such as Alzheimer’s or Parkinson’s. The difficulty here is that these models are simplifications and cannot represent the complexity of the human brain. This is likely part of the reason, why so many drug treatments have failed in later stage clinical trials.
In addition, for a long time, research in Alzheimer’s disease has focused on the accumulation of a specific protein, called amyloid beta. It is thought that the accumulation of this protein is central to causing Alzheimer’s disease by leading to the formation of plaques. This “amyloid hypothesis” has directed pharmaceutical research for a long time, and it has been the foundation of efforts to understand the disease for almost 25 years. The hypothesis has recently been questioned after failed drug trials, and the role of amyloid beta remains a controversial topic amongst researchers. What has become evident is that there are many different factors that play a role in Alzheimer’s disease, and amyloid beta is one of them. How it interacts with other proteins and processes in the body remains to be determined, as researchers try to unravel the complexities of this particular disease. Once we have a detailed understanding of the underlying mechanisms of the role of amyloid beta in Alzheimer’s, we will be able to develop successful treatments using a bottom-up approach.
It is that likely no single treatment will allow us to cure neurodegenerative diseases, such as Alzheimer’s disease. Instead, we need to develop multi-target therapies, in which we tackle all the different aspects that are affected by the disease. Based on this concept, we have developed both of our apps CogniStrength and CogniCare, which provide comprehensive support for people living with dementia and their caregivers respectively. We hope that using a holistic approach will allow those affected by dementia to improve their quality of life.