The film shows the cruelty of Alzheimer’s disease and the impotence of medicine. However, scientists continue to work on new drugs and methods to quickly detect the early symptoms of the disease, because this could be the key to stopping the disease in the future. So that it does not reach the stage that killed Augusto Gongora and today slowly kills 55 million people worldwide.
It’s on the tip of my tongue!
And it starts killing people much earlier than previously thought. The early subtle symptoms of Alzheimer’s disease and the changes it causes in the body are visible long before the patient or family notice any impairment of cognitive function or memory. As researchers at the University of Toronto recently demonstrated, early signs of the disease can be detected in speech long before more obvious symptoms appear. Most of us associate dementia with problems such as forgetting words or names of specific things, but it turns out that a better indicator of the early stages of degenerative changes in neurons is not the quality of speech, but its speed.
A team of researchers led by Dr. Hsi Tiana Wei of the University of Toronto discovered this in a study involving 125 healthy adults between the ages of 18 and 90. The researchers asked these people to describe in detail the scene shown to them in the photo, recorded these descriptions, and then analyzed them very carefully with the help of artificial intelligence. They mainly wanted to isolate characteristics such as speech rate, length of pauses between words, and the variety of words used. It turned out that artificial intelligence was able to detect neurodegenerative changes much faster by measuring a person’s speech rate – a person with such changes in the brain takes longer to search for several words in memory, although they are not yet aware of it, and the slowdown is not noticeable to others.
There have been signs that early signs of Alzheimer’s disease can be detected in speech and that artificial intelligence can be very useful in this regard. In 2019, researchers at Arizona State University conducted an unusual study in which they instructed artificial intelligence to compare spontaneous, unread speeches by two former US presidents – Ronald Reagan, who had Alzheimer’s disease, and George Bush, who was the same age and never received the diagnosis. The researchers analyzed several recordings of Reagan’s press conferences from 1981 to 1988 – from the time when he had not yet been diagnosed and was actively in office.
However, it turned out that even then, several years before the diagnosis (Reagan received it in 1994), artificial intelligence had detected features in his speech that were very characteristic of dementia, including: a decrease in the number of single words used in speech, an increase in the number of word fillers – in English, for example: “well”, “basically”, “actually” – as well as an increase in the number of non-specific words, such as “something”, “someone”. George Bush’s AI did not detect any changes in the quality of speech while he was in office.
The blood will tell you the truth
However, even early detection of speech disorders is still not sufficient for truly effective treatment. – When even subtle changes in the way people speak appear, it means that the disease has already entered the clinical, symptomatic phase, and we want to intervene in the preclinical phase, when there is no brain damage yet – explains Prof. Konrad Rejdak from the Medical University of Lublin. – Today we are looking for so-called biological markers, i.e. specific substances whose presence will indicate the risk of neurodegenerative changes in the brain and various subtypes of dementia, which today are collectively called Alzheimer’s disease – says Prof. Rejdak.
Scientists from the Institute of Bioengineering of Catalonia (IBEC) and the University of Barcelona have recently discovered a substance that could be a promising biomarker for Alzheimer’s disease in the future. They examined the brains of people who died with Alzheimer’s disease at various stages and found that the brain tissue of people who died at a very early stage of the disease was extremely abundant in a certain microRNA molecule called miR-519a-3p. The researchers noted that as the disease progresses, the level of this molecule in the brain decreases, while the amount of the protein tau, which has previously been linked to the development of Alzheimer’s disease, increases. It turns out that an unusually high level of miR-519a-3p may be the indicator that doctors look for before any symptoms appear.
– In our study, we compared the levels of this biomarker in brain samples with other diseases, including Parkinson’s, and confirmed that the changes in miR-519a-3p are specific to Alzheimer’s disease, says neurobiologist Dr. Rosalina Gavín from IBEC. Now the scientists are checking whether it is possible to easily determine the level of this molecule in peripheral blood to create a simple test for the early detection of Alzheimer’s disease.
Genes or neurotoxins?
There is currently no widespread access to advanced methods for early diagnosis. “Most often, the patient comes to the doctor quite late, when the neurodegenerative changes in the brain are already advanced,” says Dr. Natasza Blek from the Maria Skłodowska-Curie Medical University in Warsaw. “Most often, the first signs that raise suspicion of Alzheimer’s disease include, for example, losing things or asking the same question many times. Patients also have difficulty remembering what they did a few hours ago. The symptoms progress over time,” says Dr. Blek.
The problem of early detection of this disease is also related to the fact that the cause is still unknown. Neurologists believe that it is a disease resulting from genetic and environmental factors. – There is a genetically determined early form of Alzheimer’s disease, but it is very rare and accounts for several percent of all cases. The vast majority of cases are sporadic and have no direct link to a specific genetic mutation, emphasizes Dr. Blek.
Very early symptoms of Alzheimer’s disease can be detected in speech long before more obvious symptoms appear
Previous research also suggests that education level and socioeconomic factors are associated with a higher incidence of Alzheimer’s disease in poor and uneducated people. – Recently, there have been reports that poor oral hygiene may increase the risk of the disease. A few years ago, research findings were widely reported showing that neurodegenerative processes are significantly accelerated by poor sleep quality and various factors that reduce nighttime sleep, such as shift work and night shift work, says Dr.
Finland is an interesting research area for scientists trying to understand the mystery of Alzheimer’s disease. The country has had the highest incidence of the disease in the world for years, but Finns do not have more genetic mutations than other nations that predispose them to it. So what makes them suffer from dementia so often? It is possible that neurotoxins in the Finnish environment are to blame, says Dr. Arnold Eiser of the University of Pennsylvania. The Finnish climate is damp and cold, which favors the growth of fungi that produce mycotoxins that are poisonous to the brain. And a cyanobacteria appears in Finnish lakes, producing another neurotoxin. In addition, Dr. Eiser writes in Brain Research, Finnish soils are low in selenium, a trace element that helps the human body neutralize toxins. But more research is needed here, Dr. Eiser says.
Recently, a completely new lead in the research into the cure for Alzheimer’s disease has emerged – the brain microbiota, that is, bacteria that naturally inhabit our central nervous system. Until now, microbiota has most often been mentioned in the context of bacteria that inhabit the intestines or the skin, but a 2023 study from the University of Edinburgh showed that several species of bacteria similar to those that live in the human gut also live permanently in the human brain.
However, scientists analyzed brain tissue samples not only from healthy people, but also from people who died from Alzheimer’s disease, and discovered something surprising – in the brains of sick people there was a large overrepresentation of certain species of bacteria (mainly Streptococcus, Staphylococcus/Bacillus) and fungi from the Aspergillus, Candida and Schizophyllum groups. According to researchers, this may suggest that infections associated with a decrease in immunity with age may be the main cause of Alzheimer’s disease. But in this case, the cause-and-effect relationship has not been confirmed, and scientists have no idea how bacteria and fungi enter the brain.
Fighting plates
Regardless of the cause of Alzheimer’s disease, doctors observe similar changes in the brain of all patients. – This disease is accompanied by the deposition of specific deposits, so-called amyloid plaques and neurofibrillary tangles in the patient’s brain. Two proteins accumulate in them – beta-amyloid and tau. They prevent effective communication between neurons and, as a result, cause degeneration of the entire brain. However, we do not yet know what triggers the deposition of these plaques – admits Prof. Rejdak. Therefore, current research into new drugs is focused on preventing the formation of these plaques. – In the USA, there are already two biological drugs registered by the FDA (Food and Drug Administration) that stimulate the immune system to fight amyloid plaques at an early stage of their deposition. However, they do not work in patients with advanced forms of the disease, because it is already too late – says Prof. Rejdak. Vaccines against Alzheimer’s disease, which are being developed by several pharmaceutical companies, are also designed to prevent the formation of amyloid plaques. According to the “New Scientist”, up to six different vaccines against beta-amyloid and tau are currently being tested.
Removing plaques that have already formed is much more difficult, although research is also looking into this. In a study in mice, scientists at the Cleveland Clinic Lerner Research Institute found that reducing the level of an enzyme called BACE-1 in the brain causes beta-amyloid plaques to break down, which can ultimately reverse the disease – at least that’s what happens in mice. However, manipulating the level of BACE-1 in the brain is dangerous – it’s also involved in the breakdown of other proteins, and its complete absence from birth results in serious neurodevelopmental defects. This has already been shown in genetically modified mice that don’t produce this enzyme. However, the Cleveland team set out to reduce BACE-1 levels only in adult mice that had been genetically engineered to develop Alzheimer’s disease. Mice that started developing amyloid plaques in their brains at 75 days of age stopped producing this enzyme by 10 months of age. They found that the plaques disappeared and the mice with advanced Alzheimer’s recovered mental function. Will the same thing happen in humans? Scientists have not yet verified this.
