by Cristina Marrone
Plasma biomarkers, effective and inexpensive, will not be able to reveal when the disease will manifest itself. The president of neurologists: An incentive to work diligently on prevention
Draw a house. Tell me what day today. List words that begin with S. Name as many animals as you can in one minute. Since the 1980s, memory tests similar to these, often performed with paper and pencil and evaluated by doctors well trained to read the results, have been the mainstay in the diagnosis of Alzheimer’s disease, a brain disorder that erodes memory and thinking until making the patient incapable of carrying out very simple activities. It is estimated that by 2050 there will be 150 million Alzheimer’s patients worldwide.
While these symptom-based tests are effective at determining when a person’s memory and thinking are not normal, they are not as effective at helping doctors uncover the cause of these disorders, which can actually result from anything from vitamin and hormone deficiencies to small strokes, from tumors to infections, from Parkinson’s-related disorders to dementia with Lewy bodies, as well as of course Alzheimer’s disease.
The limits of memory tests
Symptom-based testing is believed to be one of the reasons for this failure of trials of some drugs with the aim of early elimination of amyloid in Alzheimer’s. The review of the data of patients involved in the clinical trials of two monoclonal antibodies, bapineuzumab and solanezuma b (then interrupted due to ineffectiveness) found that approximately a third of the patients enrolled did not have the disease for which they were being treated, i.e. the accumulation of beta amyloid or tau protein in the brain, hallmark of Alzheimer’s disease. Today, obtaining a precise diagnosis is even more fundamental, especially in view of the possible arrival of new and promising drugs against Alzheimer’s. For this reason, in the United States, where monoclonal therapies have already been approved (amidst a thousand critical issues), new guidelines for the diagnosis of the disease are being discussed.
What do plasma biomarkers measure
Memory tests would take a back seat compared to other biomarkers: brain scans, spinal fluid analysis but above all the less expensive and minimally invasive plasma biomarkers which are also being talked about in
national congress of the Italian Society of Neurology underway in Naples. This type of test measures abnormal levels of amyloid beta proteins in the blood, a characteristic signal of Alzheimer’s disease, but also the presence of phospholidated tau protein and non-specific neuronal (neurofilament) damage. A positive value – comments Alessandro Padovani, director of the Neurology Clinic at the University of Brescia and new president of the Italian Society of Neurology, installed on the occasion of the congress underway in Naples – indicates the need to carry out further tests, but if negative it excludes the illness. Beta amyloid in the brain accumulates slowly over decades, typically starting in middle age, and becomes more common as we age. There are people who, despite an accumulation of beta amyloid in the brain, do not show symptoms of cognitive decline, but in patients with cognitive decline caused by Alzheimer’s there is always an accumulation of beta amyloid. For this reason it is believed that patients with cerebral accumulation of beta amyloid will sooner or later experience cognitive decline.
How PET can change the diagnosis
A large study published in Jama in 2019 by researchers from the Alzheimer’s disease research center at the University of California in San Francisco showed in concrete terms what impact these biomarkers could have. Over the course of a couple of years, scientists, led by Professor Gil Rabinovici, subjected over 11,000 patients with memory loss and changes in thinking of uncertain cause to PET with a radioactive tracer to illuminate the beta amyloid deposits in the brain. specialized centers. PET imaging of the brain changed the diagnosis in 35% of patients in the study: Alzheimer’s was ruled out in 25% of people thought to have it. Another 10% with memory problems believed to be caused by another disease were instead definitively diagnosed with Alzheimer’s. Only the clinical investigation is not enough – confirms Federica Agosta, professor of neurology at the San Raffaele hospital in Milan who spoke at the SIN congress – and we too have seen that in 15% of cases the clinical diagnosis of Alzheimer’s is wrong, even if the criteria diagnostics are best applied. The brain scan that can see the amyloid deposits and arrive at a certain diagnosis of Alzheimer’s, however, is a very expensive test, generally used for the clinical evaluation of patients enrolled in clinical trials and not for routine diagnosis.
New guidelines for diagnosis are being studied
Testing all patients with suspected Alzheimer’s through invasive spinal taps (requiring day surgery) or expensive brain scans cannot solve a massive public health problem, many scientists say. The Alzheimer’s Association and the US National Institute of Aging are studying new guidelines for the diagnosis of Alzheimer’s, which were discussed in Amsterdam in July at an international conference of the US Alzheimer’s Association. For the first time the guidelines, which are expected to be ready within the year, will direct doctors to use blood tests to detect signs of Alzheimer’s in the brain.
The role of plasma biomarkers
Research shows that plasma biomarkers are as reliable as PET or spinal fluid measurements for detecting Alzheimer’s proteins. But they are certainly less invasive and less expensive. There are many blood biomarkers studied, but so far none have been approved by a regulatory body, not even by the FDA. However, scientists around the world expect that within a few months the first tests will be available on the market. To date in the United States, amidst much controversy, a blood test that measures the biological changes associated with Alzheimer’s has been sold online directly to consumers, but patient associations are against it, deeming it premature to offer such a test directly to consumers, without mediation. of a doctor.
Approved blood tests will make diagnosis less expensive and more easily accessible for those patients who cannot easily reach specialized memory centers, says Clifford Jack, neuroradiologist at the Mayo Clinic in Rochester, Minnesota and co-author of the new American guidelines. According to Jack, the new biomarkers will allow doctors to better study the disease because Alzheimer’s markers appear in the blood before there is evidence of the disease visible on brain scans and even before symptoms appear. This will make it possible to understand at what point a patient is in the progression of the disease (the proposal of the new guidelines speaks of 6 phases and phase 1 Alzheimer’s would be the disease diagnosed with blood tests alone, without other symptoms).
Is the diagnosis even among asymptomatic people?
Alzheimer’s can therefore be diagnosed even in those who have not yet shown memory loss. The symptoms are the consequence of the disease and not the definition of the disease, underlines Jack who gives the example of type 2 diabetes: the vast majority of people who are diagnosed with diabetes during screening blood tests for fasting blood sugar do not presents any symptoms. Just because they don’t yet have kidney failure or are not yet blind doesn’t mean they don’t have the disease. Plasma biomarkers, as already underlined, are not yet available, however they will be available soon and the debate among experts, but also among patients, on the opportunity to know well in advance the positivity to a plasma biomarker and not only in the testing phase cognitive impairment. What is the point of knowing that sooner or later we will suffer from Alzheimer’s disease if there are still no effective and safe therapies? Certainly a plasma biomarker can help us in screening the population at risk to select who needs to undergo further tests and access more in-depth diagnostic procedures such as CSF analysis or PET scans and hopefully in the future ad hoc therapeutics, comments Professor Agosta. Testing positive for a plasma biomarker for Alzheimer’s in the absence of symptoms does not say when the disease will present, underlines Alessandro Padovani. A possible positivity could be a criterion for selecting patients to administer future drugs – reflects Padovani -. On the other hand, a negative value in the test in people who present one or more risk factors can reassure them that there will not be a negative evolution, at least as regards Alzheimer’s disease. Meera Sheffrin, medical director of Stanford Healthcare’s Senior Care clinic, says she is skeptical about using these tests at Cnn: A positive test will not tell you whether you will actually develop dementia, when symptoms might begin, or how high the risk is for each individual, and could lead to misunderstandings and excessive worry.
Plasma biomarkers: an opportunity for prevention
Plasma biomarkers should also be read from a preventative perspective. We have known for some time – adds Padovani – that keeping some of the
12 risk factors
identified in 2020 by a commission of the Lancet journal can perhaps avoid, but certainly postpone the appointment with a neurodegenerative disease. High blood pressure, for example, is an under-diagnosed co-factor in 60% of the population. With the right prevention, 4 out of 10 Alzheimer’s diagnoses could be avoided. Knowing that you are positive for a biomarker can only be an incentive to work with commitment and consistency on prevention, taking seriously the strategies to improve brain health with objective of changing the natural history of the disease.
The 12 Alzheimer’s risk factors on which each of us can intervene
1-Hypertension
2-Untreated hearing loss
3-Cigarette smoking
4-He will sit down
5-Obesit
6- Diabetes
7-Poor education
8-Alcohol consumption
9-Air pollution
10-Brain trauma
11-Consumption of alcoholic beverages
12-Passive smoking
October 23, 2023 (modified October 23, 2023 | 07:56)
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