Filenews 24 September 2023 - by Xenia Turki
At first he did not remember where he put his keys and other items. Then things became more serious. He forgot business appointments, confused dates, and wasn't sure what words he used. The day he couldn't orient himself and go home, an alarm sounded. The doctor's diagnosis left no room for optimism. Alzheimer 's.
It is estimated that more than 50 million people today around the world suffer from dementia diseases, the most common of which is Alzheimer's. The number will increase dramatically in the future due to increasing life expectancy in both developed and developing countries. However, a much greater number are suffering, as the burden of the disease is borne by the families and caregivers of dementia patients.
September is Alzheimer's Awareness Month. In his interview with Phileleftheros, Nikos Skarmeas, Professor of Neurology at the National and Kapodistrian University of Athens, talked about what causes the disease and to what extent we can, if not prevent, at least delay its onset. Hopes for tackling the disease are, however, raised by the recent approval of new drugs by the US Drug Administration. Although there are many uncertainties, we can be optimistic that with small steps we are moving into a time when Alzheimer's will be a treatable disease.
Dementia isn't exactly the same as Alzheimer's, is it? What are their differences?
-Dementia means the depriving "a" and the word mind. I lose my mind. So dementia is a mental dysfunction, that is, our mind does not function properly. If someone has dementia, the next question is why they are doing it. Of the diseases that cause dementia, the most common is Alzheimer's. So Alzheimer's is a specific disease that causes dementia. A substance called amyloid accumulates in the brain, causing the brain to malfunction.
Do we know exactly what causes Alzheimer's?
We know that 60% to 70% are genetic factors and the rest are non-genetic factors. The biological process is what I mentioned at the beginning that the brain overproduces starch and cannot drain it, so it accumulates and little by little over the years fills up. This creates a toxic environment in which the brain cannot function.
Do we understand why the brain reaches the point of producing so much amyloid?
-In essence, it is true that 60% to 70% are genetic factors and the rest are non-genetic factors. Maybe it has something to do with our lifestyle. But it is not clear why this is happening. To some extent it is hereditary and to some extent not.
So if someone has the relevant genes, is it inevitable to get Alzheimer's?
-The issue is complex. There are many genes associated with the onset of the disease and each of them plays a small role, has a small effect. The more of these genes a person inherits, the more likely they are to develop the disease. Beyond that, however, we know that it is not a completely deterministic expression of these genes, so the predisposition increases, but when and if the disease will occur is influenced by other factors. Genes are not fully determinant, with the exception of a rare inherited form of the disease. Of the 100 people who have developed Alzheimer's, 99 have the sporadic form, where the many genes with little effect play a role. The absolutely inherited form is only in the 1%, where three very specific genes play a role. If someone has them, they will develop the disease, possibly at a young age.
What are the non-genetic factors associated with the onset of Alzheimer's?
-In general, what seems to protect the heart has a protective role for the brain as well. The regulation of diabetes and cholesterol and lipids, control of hypertension and obesity, smoking, healthier diet, exercise, mental and social activity, avoidance of traumatic brain injuries are some factors. We also have evidence that environmental pollution and fine particles may play a role, as may hearing loss. In addition, there are factors that may give greater reserves, namely the quality and quantity of education and intellectual and more demanding professions. All these and many others contribute to increasing or even decreasing the risk of developing the disease.
So, what can someone do if not to prevent at least to delay the onset of the disease?
-Taking into account the factors associated with Alzheimer's, he should control vascular risk factors, cholesterol, pressure, sugar, weight, avoid smoking and have physical and mental activities. Take care of their diet and live in a healthy environment. In general, what helps us lead a healthier life seems from many studies to have a positive effect and modifies to some extent the likelihood of someone developing or not developing the disease. Any delay in the onset of the disease is significant. Someone, for example, may be genetically predisposed to develop the disease at the age of 75. Taking into account the factors we have mentioned, he delays the disease until his 80s. That's profit. Many times when the disease develops, patients say we did what we had to do and got sick in our 70s or 75s. However, they may have had a greater genetic predisposition if they did not
Some experts classify Alzheimer's as an autoimmune disease. What is your opinion?
There is not much convincing evidence that Alzheimer's is an autoimmune disease. It is considered to belong to the category of degenerative diseases and not autoimmune.
-Would you advise someone who has cases of dementia and Alzheimer's in their family to get tested and know if they will get sick at some point in the future? Or can this prove to be an unbearable burden since the disease currently has no cure?
First of all, we cannot say with certainty whether someone will get sick. At the same time, however, we know that amyloid damage in the brain begins 15 to 20 years before the onset of the disease and that it builds little by little year after year. We can measure the amount of amyloid either with imaging methods or more often with lumbar puncture. The trend now is to develop drugs that can fight starchoid. Therefore, people who have reasonable grounds to worry may have reasons in the future to take these tests.
-You come into contact with many dementia patients. Do you have any idea what's going on in these people's minds? Have their memories been completely erased like when we format our computer or do they exist somewhere and are simply not accessible?
It is a course of many years. In the beginning the problem is small and the memories and especially the most recent ones fade, while as time goes by the older ones fade away. Some patients are sensitive and aware, some less so. It is not a momentary phenomenon but a course of eight, ten years and it is different for each patient. Memories, therefore, depend a lot on the stage of the disease.
-Are patients aware of their condition? Not that they don't remember, but do they realize what the course will be?
-In the initial stage, they are aware that memory is impaired, that is, when they are in the stage of mild mental disorder. But when they enter the stage of dementia, two-thirds of patients are not insightful, they are not even aware. That's why they often don't want to seek medical help. That is why it is the caregivers and those close to them, who take it upon themselves and sometimes with difficulty to persuade them to go to the medical services. And that they are not aware, you know, is both a wish and a curse. And we know that's because the damage that occurs in this disease also affects brain centers that do brain overview, coordination, and surveillance.
Dementia and Alzheimer's are diseases that tear both patients and their caregivers apart. What advice can you give them?
It is a difficult disease with great cost for patients and caregivers. What I can say is for caregivers to try to be informed as much as possible and ask for help because it takes many years. Dementia is not a sprint but a marathon, which is why caregivers cannot cope on their own. They need to think long-term and keep reserves to take care of both patients and themselves.
Hopes from new drugs
In recent months, some formulations such as Leqembi and Donanemab have been approved by US authorities. It is likely that we will soon see them circulating in the European Union as well. What's new with these drugs for Alzheimer's patients?
These drugs are really revolutionary in the sense that what they do is remove starch from the brain. They are monoclonal antibodies and have a more causal approach to the disease, while the formulations we have now are like patching up some neurochemical systems of the brain, which are affected by amyloid and therefore do not strike at the root of the evil. But this seems to be what the new drugs are doing. They are the first Alzheimer's drugs we have in 20 years. It is very promising that we have something new and that they are targeting the starch itself. What we see is that they slow down the development of the disease by about 30%. That is, in the three years of illness the patient gains one. This may not sound so impressive, but it is important and generates optimism for the future.
But these drugs are very expensive. How can we ensure that everyone who needs them will have them?
-This is a huge issue. The prices that the United States got are very high. In a recent publication it was calculated that if Europe gets these medicines at these prices it will account for half of the total budget for all medicines for all diseases. So it is impossible for Europe to have these medicines at such prices. Because the numbers are so big, we will have a problem even if prices fall by either half or a quarter. And the reason is that there are many candidates who could take the drugs. However, developments are ongoing and at the same time there are enough elements that we do not know, for example for how long these drugs should be taken.
On the other hand, the cost of caring for a dementia patient is huge.
-This is something that is true. And let's say that the cost calculation for the new drugs we have talked about was done with models that do not take parameters such as the care and good life of a dementia patient.
Do you think we will one day be able to cure Alzheimer's? How far is this day?
No one can say for sure when that day will come. But it is a process with many, small and sequential steps because it is a complex disease associated with old age and moreover it is a heterogeneous disease.
