The revised diagnostic criteria seek to avoid overdiagnosis of Alzheimer’s disease

The diagnosis of Alzheimer’s disease (AD) currently relies heavily on the presence of biomarkers. This can lead to problematic overdiagnosis if misinterpreted.

To address this problem, a global group of experts led by the Hôpitaux universitaires de Genève (HUG), the University of Geneva and the Salpêtrière Hospital drew up recommendations. Based on a review of the scientific literature, they argue that clinical signs as well as biomarkers should be considered. This new approach avoids diagnosing AD in people with abnormal biomarkers who will never develop memory disorders and establishes a follow-up process tailored to each individual. These recommendations have been published in the Journal of the American Medical Association – Neurology (JAMA Neurology).

According to the Alzheimer Suisse Association, by 2050 the number of people in Switzerland affected by AD and other forms of dementia will exceed 300,000, which is twice as many as today.

To facilitate research on this disease, three months ago a group of scientists in the United States defined new, much broader diagnostic criteria. For them, the diagnosis of AD would be determined by the sole presence of biomarkers, such as amyloid β and tau protein, without considering memory function and other cognitive functions. These biomarkers are quantifiable in cerebrospinal fluid, PET brain images, or blood and have been associated with the brain degeneration that causes AD.

For the global team of experts led by Professor Giovanni Frisoni, Head of the Memory Center at HUG and Full Professor, Department of Rehabilitation and Geriatrics at the UNIGE School of Medicine and Professor Bruno Dubois, Professor of Neurology at the Sorbonne University and Head of Department at the Salpêtrière Hospital in Paris , the impact of these new criteria will be that many perfectly healthy people will be diagnosed with AD on the sole basis of laboratory testing, while never developing memory impairment. Therefore, they formed an expert group to issue new recommendations.

A clinical and biological definition

According to professors Frisoni, Dubois and their colleagues, biomarkers are only useful if they are related to a multidisciplinary medical consultation and memory tests. These tests may reveal short-term memory problems, that is, the inability to retain recent information. Affected individuals may also lose their bearings and become disoriented. They will often have difficulty speaking, finding their words, or their reasoning will become less clear. Finally, behavioral changes such as irritability, anxiety, depression and social isolation sometimes occur.

This diagnostic nuance is crucial for people who have positive biomarkers but do not manifest clinical symptoms. If they represent only 3% in the 50 to 59 age group, this percentage rises to 40% in the 80 to 89 age group. Based on the Alzheimer’s Association of America criteria, all of these individuals would qualify for a diagnosis of AD. However, for Professor Frisoni, “70% of all these people will never develop AD”. So why give them this painful diagnosis?’

New categories

The international panel’s recommendation ends up reconsidering biomarkers not as equivalents of AD but simply as indicators of the deposition of toxic proteins that accompany the disease. This nuance allows defining two categories of individuals with abnormal biomarkers, those with abnormal memory tests and those with normal tests. The first group has AD while the second group only has an increased risk of developing AD, but does not yet have it. Therefore, they are not considered sick, but rather at risk.

A new patient journey in Geneva

Within the clinical context, these categories enable the development of new monitoring strategies for at-risk and currently untreated individuals. In Geneva, changes to best practices are already underway. “We received funding from the State of Geneva for four years so that at the beginning of 2025 our Memory Center can offer a new patient journey for people at risk. These trips will also include an assessment of all known risk factors, including biomarkers, but also depression and social isolation.”

Future research challenges

The formulation of these two categories of individuals is also important for research, as they will allow the creation of better stratified longitudinal cohorts. “The weight of each risk factor is quite imprecise at present, explains Professor Frisoni, and adding these categories to longitudinal studies will allow us to quantify the weight of each factor much more precisely.”

The inclusion of asymptomatic subjects in clinical trials will also allow testing the effectiveness of treatments, including amyloid-reducing agents, that seek to reduce the risk of AD and associated cognitive impairments. “In the long term, we envision personalized therapies based on lifestyle and nutritional principles, such as probiotics, as well as anti-amyloid drugs, tailored to the individual’s risk profile,” concludes Professor Frisoni.