Alzheimer's disease is increasingly diagnosed long before the appearance of the first symptoms — based on tests and brain scans. However, there is still no consensus in the medical community on whether biological markers should be considered an independent and sufficient basis for diagnosis.
Illustrative image. Photo: vecteezy
Imagine you are over 60, and you have been diagnosed with Alzheimer's disease. You begin to radically revise your plans: preparing your loved ones for the fact that sooner or later you will lose your capacity, researching options for specialized care, and rushing to fulfill as many items as possible from your bucket list. However, six months later, another neurologist stuns you with an opposing conclusion: you do not have Alzheimer's disease, nor even a risk of its development in the near future.
As reported by The Wall Street Journal, conflicting diagnoses are becoming an alarming reality due to the existence of two different systems of official criteria. This entails not only psychological trauma but also the risk of unnecessary aggressive treatment. At the heart of the discussion lies a fundamental question: how exactly to define the disease — as a purely biological condition based on biomarkers, or as a complex clinical diagnosis that requires the obligatory presence of symptoms.
Two Approaches to Diagnosis
The first approach, enshrined in the 2024 Alzheimer's Association criteria, defines the disease through biology — specifically, through the presence of amyloid protein in the brain. Proponents of this model argue that the pathology begins to develop approximately 15 years before the appearance of the first cognitive impairments.
They emphasize an important technical nuance: modern testing methods — positron emission tomography and cerebrospinal fluid analysis — are capable of detecting amyloid only when it has already accumulated in significant quantities. In the early stages, when there is still little protein, these methods remain ineffective.
Furthermore, Alzheimer's disease is associated not only with amyloid but also with another pathological protein — tau, which damages neurons and is considered a more direct cause of cognitive decline. Therefore, a positive test result usually means that the pathological process has been ongoing for more than a year and is often accompanied by the accumulation of tau biomarkers. From this point of view, cognitive symptoms are a late manifestation of the disease and are not considered a mandatory condition for its biological definition.
However, the International Working Group, which unites scientists and neurologists from around the world, proposes a stricter standard. According to their criteria, a diagnosis requires a combination of three elements: the presence of amyloid, tau biomarkers, and clear cognitive symptoms. This group of experts sees a dangerous semantic problem in the biological approach — the blurring of the concepts of 'disease' and 'risk'.
They compare the presence of amyloid to high cholesterol levels: just as high cholesterol is a risk factor but does not mean a heart attack will occur, so amyloid does not always lead to dementia. Statistics show that 25% to 45% of elderly people who have no memory complaints are carriers of amyloid, but most of them will never develop the disease in a clinical sense.
When Biomarkers Determine Treatment
An important point of agreement between both camps is that people without symptoms should not be tested or treated in routine clinical practice. Even proponents of the biological approach insist: until clinical trials are completed that confirm whether early application of anti-amyloid drugs can prevent dementia, monoclonal antibody therapy should only be prescribed to those who already have cognitive impairments.
This is due to the high risk of serious side effects, such as strokes. Nevertheless, there are concerns that in practice these recommendations are not always followed, and treatment may begin immediately after the first positive test.
There is also a serious clinical risk that the detection of amyloid in a patient with memory complaints may narrow the focus of diagnosis. In such cases, a positive biological test result sometimes becomes a decisive argument, leading doctors to ignore other possible causes of the condition.
However, cognitive impairments can be caused by vascular brain diseases, chronic stress, sleep disturbances, or natural age-related changes. If biological markers are not the primary cause of the clinical picture, there is a risk of prescribing unnecessary and potentially dangerous treatment, while the true problem remains unresolved.
The scale of this problem is measured in millions of lives. With a purely biological definition of the disease, in the US alone, approximately 47 million people could be classified as ill based on the presence of biomarkers. Critics of this approach warn that this could lead to a situation where a vast number of people are considered ill solely on the basis of biomarkers, despite the absence of clinical manifestations.
Until the medical community reaches a consensus, specialists advise patients to refrain from unnecessary tests. This is especially pertinent given the emergence of easily accessible blood tests, which could trigger a wave of erroneous diagnoses and unjustified anxiety in society.
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