Alzheimer’s has an immense economic and social cost in the world: already, in 2014, it was estimated at 1,000 billion dollars annually. At the Global Action Against Dementia event that I hosted in Ottawa that year, politicians, researchers and pharmaceutical industry representatives came together to take stock of the comprehensive strategies needed to end dementia, including Alzheimer’s disease. Their consensus at the time: if no effective drug was launched before 2020, humanity was heading for a wall. An unprecedented crisis, both humanitarian and financial, was to be expected.
Today, in 2021, more than half a million Canadians have this disease, but nothing seems to have changed. “The wall is still in front of us. The financial and human repercussions are greater than ever and we still do not have the miracle drug. The only good news is that the curve for the number of new cases is sagging a bit, thanks to an improvement in the general health of the population, ”says Yves Joanette, researcher in cognitive neuropsychology of aging and assistant vice-rector of the population. research at the University of Montreal. Having organized the 2014 meeting and then chaired the World Dementia Council, he has an overview of the current effort to reach solutions.
A progressive disease
“Today, we see Alzheimer’s as a disease that evolves over time. We know that its trajectory begins 25 to 30 years before the onset of symptoms, that there are different forms of the disease and that many factors influence its onset and its evolution, ”explains the researcher, who remains optimistic about an increasingly complex challenge.
The pathology of Alzheimer’s is characterized by two distinct signatures. The first, which can be detected with magnetic resonance, is the gradual appearance of tiny plaques made up of a small protein, amyloid. These spots gradually invade the surface of the brain, the cortex, and then the hippocampus, the seat of long-term memory. The disease also attacks the inside of neurons with the abnormal production of a protein called “tau”, which accumulates in these cells and affects their functioning. Many drugs have tried to target and stop the progression of these protein clumps, but without success.
“Some people have these amyloid plaques and don’t develop the disease. So there is something more operating here. It is believed that other vascular and inflammatory factors, or perhaps even certain viruses, contribute to the development of the disease, ”says Yves Joanette. Recently, many cells of the immune system have been found in patients’ brains, which appear to stimulate the creation of amyloid plaques and tau proteins. Other researchers have also made an association between the pathology and viruses, including herpes simplex type 1, responsible for the very common “cold sore”. Many laboratories are currently working on these tracks.
Pathways for the future
During his time as President of the World Dementia Council from 2016 to 2018, Yves Joanette also developed a comprehensive approach research on two fronts: promoting therapies aimed at slowing the onset of symptoms while developing palliative treatments to improve the quality of life of patients.
For him, the dream treatment, “nirvana” as he puts it, would be to achieve a method similar to that used for cardiovascular diseases, which often also appear with age and which are linked to poor lifestyle habits. “If we could find the equivalent of a statin (used to lower cholesterol) for Alzheimer’s disease, paired with lifestyle recommendations – diet, exercise for body and mind – we would have taken an important step, ”he says. The ultimate goal would be to delay the onset of symptoms to make the illness of shorter duration, which is called “morbidity compression”. Going from a decade of debilitating symptoms, on average, to just a few months would be a huge step forward.
But the biological mechanisms in the brain that lead to dementia are far more complex than those that raise blood cholesterol levels. Yves Joanette believes that another important avenue to explore to tackle the disease is the development of a “cocktail of chemical markers” to try to make an early diagnosis by a simple blood test. This is already done with brain imaging, but it is an expensive method and its universal access is not realistic.
When I ask him to give me a prediction of the state of play for the year 2030, Yves Joanette smiles broadly and replies that we are currently much better equipped than 10 years ago, because we understand better. and better the different mechanisms of action of Alzheimer’s. For him, success will inevitably require the work of multidisciplinary teams to tackle all the dimensions of this condition. “There will not be a great discovery that will revolutionize the treatment, but rather an assembly of several approaches which will give a result taking into account the complexity of the disease”, affirms this researcher who has devoted a large part of his life to a better understanding of the aging of the brain. He concludes that in the meantime, it is absolutely necessary to improve the quality of life for both patients and caregivers, because more than 560,000 Canadians, including 150,000 Quebecers, are affected by this disease, and this number will have doubled in 20 years.
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