Developing an Action Plan
While only a limited number of governments have begun to develop action plans to deal with the Alzheimer’s epidemic in their country, the results of their work will help guide other governments in the future. While the action plans of those countries that have implemented them do vary, overall these plans are designed to raise awareness, improve education, improve care and garner more money for research into the disease. Research funding would go towards the search for “cures” and early diagnosis, among other things that will be detailed later. Several countries initiated Alzheimer’s disease action plans during the first decade of this century. The countries showing this foresight include Australia, Denmark, England, France, Korea, the Netherlands, Norway and Sweden, among others. For example in 2008, President Sarkozy implemented the third “French Alzheimer Plan” at a cost of 1.6 billion Euros. The success of this plan was validated three years later in 2011, leading to another three-year plan being implemented. Others, such as the US and many European countries, have plans under development. In contrast, some countries such as Canada did not have a national strategy at the time this book was written. In spite of the initiatives taken by many countries, most still are ill prepared to face the reality of the Alzheimer’s epidemic. Later in the book, we’ll discuss what is and what can be done to reduce these numbers and costs.
Chapter 3
The Stages of Alzheimer’s Disease
There are a multitude of reasons why it is critical to precisely determine the stages in the progression of Alzheimer’s disease. For family members, it’s essential to accept the severity of the disease so that they can make decisions about whether home care is sufficient or whether their parent or grandparent should move into a long-term care residence. For the family physician, knowledge about the status of the patient can guide him or her in suggesting the appropriate therapy. For researchers, defining the exact stage of progress of the disease is paramount. Only when the stages of Alzheimer’s are well defined can effective and meaningful research be done.
Historically, much of the work to date on the disease has simply led to developing more meaningful and appropriate staging criteria. But even today, Alzheimer’s research groups are fine-tuning their definitions not only of the stages but also of the specific changes that occur at each stage. As more clinical indicators of the disease are discovered, it may one day be possible to determine exactly when the disease starts. One thing we do know is that the symptoms of Alzheimer’s don’t appear until long after the disease has been set in motion.
The Onset and Progression of Alzheimer’s Disease
Since Alzheimer’s disease starts long before there are any overt symptoms, this makes the search for causes and a cure much more difficult. Figure 3.1 provides a simple summary of how the as yet undetermined initiating events precede the presymptomatic phase. As its name implies, a person shows no symptoms during the presymptomatic phase. The presymptomatic phase is followed some time later by the actual symptoms of the disease where initially observed cognitive deficiencies often progress over time. As we will learn, there are some known predictors of Alzheimer’s disease. There are certain genes that are linked to the disease, for example, but the actual initiating events that drive the onset of the disease are not known.
Figure 3.1. The onset and progression of Alzheimer’s disease.
So, after the ground has been laid for the disease, it is followed by a long presymptomatic phase where the person appears completely normal and exhibits no cognitive deficiencies. Their memory is good, they recognize friends, family and items; they relate to the world around themselves. But during this time changes in the brain are occurring which will alter how their brain cells talk to each other. This progressive failure in brain cell communication underlies the events that will define the symptomatic phase, because without normal brain cell intercommunication, cognitive deficiencies become evident which usually can progress to greater brain malfunction.
The goal of biomedical research, and the underlying focus of this volume, is to study the progression of Alzheimer’s disease from the events that initiate it through to the final changes that face individuals who develop full-blown dementia. As summarized in Figure 3.2., by asking and answering specific questions at each stage, not only can the disease be better understood but new therapies can be developed. For example, by answering the question, “How does the disease start?” researchers will ultimately answer the question of how to cure the disease. The value will be the ability to stop the disease before it starts. This, of course, is the most challenging issue. After all, how can you study something that apparently hasn’t happened yet?
Knowing what happens in the presymptomatic phase prior to the onset of cognitive deficiencies will allow biomedical researchers and pharmaceutical companies to find ways to slow or prevent the progress of the disease. Of course, the problem is determining when that phase exists when there are no symptoms that are evident. This is where the role of biomarkers comes into play as detailed in Chapter 11. Dissecting out the underlying brain changes that precede the onset of mild cognitive impairment will reveal targets that can become the focus of interventions aimed at slowing or stopping the progress of the disease.
Figure 3.2. Asking and answering questions about the onset and progression of Alzheimer’s disease. MCI, mild cognitive impairment.
Figure 3.3 summarizes these events, relating them to the underlying changes that are occurring in the brain and the specific stages of Alzheimer’s disease. As we progress through this volume, we will learn more about each of these topics. There are known underlying brain changes that occur during Alzheimer’s disease. While the actual initiating events and underlying biochemical changes are not known, during the presymptomatic phase, a substance called amyloid beta begins to accumulate (Figure 3.3., top). As mentioned in Chapter 1 and detailed in Chapter 6, amyloid beta peptides will accumulate to form amyloid plaques, one of the hallmarks of Alzheimer’s disease. As this occurs the disease is progressing into the mild cognitive impairment stage of the symptomatic phase (Figure 3.3., bottom). Neurofibrillary tangles (NFTs; Chapter 7) begin to form and, coupled with the amyloid plaques, lead to progressive neurodegeneration that is linked to brain cell miscommunication and death. These events begin to transform the symptomatic phase from the mild cognitive stage to dementia as detailed later in this chapter.
Figure 3.3. Events and changes linked to the onset and progression of Alzheimer’s disease. Aβ, amyloid beta; NFTs, neurofibrillary tangles; MCI, mild cognitive impairment.
In support of this model, a study published at the end of 2012 in Lancet Neurology revealed that the appearance of amyloid beta occurs during the presymptomatic phase long before there are any overt symptoms of the disease. As the disease progresses, amyloid plaques form from accumulations of amyloid beta and other components. The accumulated evidence argues that the appearance of plaques is followed by another hallmark of Alzheimer’s disease, the formation of neurofibrillary tangles (NFTs). Working on both the outside (plaques) and inside