The diagnosis of Alzheimer’s disease (AD) is today mainly based on the presence of biomarkers, which can lead to problematic overdiagnosis if the latter is misinterpreted. To counter this problem, an international study group led by the University Hospitals of Geneva (HUG), the University of Geneva (UNIGE) and the Pitié-Salpêtrière hospital group has issued recommendations. Based on a review of the scientific literature, they advocate taking into account clinical signs in addition to biomarkers. This new approach makes it possible to avoid making a diagnosis of AD in people with abnormal biomarkers, who will never develop memory disorders, and to implement monitoring adapted to each individual. These recommendations were published Friday in the Journal of the American Medical Association – Neurology (JAMA Neurology).
According to the Swiss Alzheimer Association, the number of people suffering from AD and other forms of dementia in Switzerland will exceed the 300,000 mark in 2050, double the number today.
To facilitate research into this disease, a group of scientists in the United States defined new, very broad diagnostic criteria three months ago. For them, the diagnosis of AD would be defined by the sole presence of biomarkers, such as amyloid β and tau protein, without taking into account the functioning of memory and other cognitive functions. These biomarkers are quantifiable in the cerebrospinal fluid. spinal, on PET brain images or in the blood and have been associated with the brain degeneration caused by AD.
For the international working group led by Professor Giovanni Frisoni, head of the HUG Memory Center and full professor in the Department of Rehabilitation and Geriatrics of the Faculty of Medicine of the University of Geneva, and Professor Bruno Dubois, professor of neurology at Sorbonne University and head of department at the Salpêtrière hospital, these new criteria will have the effect that many perfectly healthy people will be diagnosed with AD on the sole basis of a laboratory examination, whereas they will never develop memory problems. Therefore, they formed a group of experts to issue new recommendations.
A clinical and biological definition
According to Professors Frisoni, Dubois and their colleagues, biomarkers are useful only if they are combined with a multidisciplinary medical consultation and memory tests. These tests can reveal short-term memory problems, i.e. the inability to store recent information. Affected people can also lose their bearings and become disoriented. They often have difficulty speaking, finding their words or have less clear reasoning. Finally, behavioral changes sometimes appear: irritability, anxiety, depression and social isolation.
This diagnostic nuance is crucial for people with positive biomarkers, but who do not show clinical symptoms. If there are only 3% in the age group of 50 to 59 years, this is the case for 40% of people between 80 and 89 years old. According to the criteria of the American Alzheimer’s Association, all of these people should be diagnosed with AD. However, for Professor Giovanni Frisoni, “among all of these people, 70% will never develop AD. So why give them this anxiety-provoking diagnosis? »
Two new categories
The international team’s recommendation amounts to considering biomarkers not as equivalent to AD, but as simple signs of the deposition of toxic proteins that accompanies the disease. This subtlety makes it possible to define two categories of people with abnormal biomarkers: those with abnormal memory tests and those with normal tests. The former have AD, while the latter only have an increased risk of developing AD, but do not yet have it. They are therefore not considered sick, but at risk.
A new patient itinerary in Geneva
In the clinical context, these categories allow the development of new monitoring strategies for people at risk who are not currently supported. In Geneva, the change in best practices has already started. “We have received funding from the State of Geneva over four years so that our Memory Center can offer a new patient itinerary for people at risk from 2025. These itineraries will notably include an assessment of all known risk factors, such as biomarkers, but also depression and social isolation for example. »
Future research challenges
The addition of these two categories is also important for research, because they will make it possible to create better stratified longitudinal cohorts. “The weight of each risk factor is currently quite crude,” explains Professor Giovanni Frisoni, “and the addition of these categories in long-term follow-up studies will allow us to quantify the weight of each factor much more precisely” . The inclusion of people without symptoms in clinical trials will also make it possible to test the effectiveness of treatments aimed at reducing the risk of developing AD and the cognitive deficits associated with it. “Ultimately, we envisage personalized treatments based on lifestyles, nutritional principles such as probiotics and also anti-amyloid drugs, depending on the risk profile of the individual” concludes Professor Giovanni Frisoni.
JAMA Neurol. doi:10.1001/jamaneurol.2024.3770
View the English version of this press release
Also read our press release of February 15, 2024 on the European consensus for the diagnosis of AD
