Early detection of Alzheimer’s disease has undergone a shift recently with the incorporation of biomarkers that allow for the identification of brain changes even before the first symptoms appear. However, the application of these new diagnostic frameworks—focused exclusively on biological parameters—raises clinical, ethical, and social questions that remain unanswered.
In this context, the article “On the complexity of biomarker-driven diagnoses of Alzheimer’s disease”, recently published in the Journal of Neuropsychology, reflects on the challenges and risks of diagnosing the disease based solely on the presence of -amyloid or phosphorylated tau in the brain. This is especially true for individuals who show no cognitive impairment. The paper is authored by Dr. Miguel Ángel Santos-Santos, a researcher in the Neurobiology of Dementias group at the Sant Pau Research Institute (IR Sant Pau) and neurologist at the Memory Unit of Hospital de Sant Pau. Together with Dr. Stephanie Grasso and Dr. Alexandra Leigh Clark, both from the University of Texas at Austin.
“Biomarkers are a promising tool, but we cannot yet consider a positive result as a diagnosis in itself. In cognitively healthy individuals, it’s more responsible to interpret them as indicators of elevated risk,” says Dr. Santos-Santos. The article highlights that a significant portion of people with abnormal biomarkers never go on to develop dementia, likely thanks to mechanisms of cognitive reserve and brain resilience. This concept, influenced by factors such as educational level, life experiences, and sociocultural context, is key to understanding the progression of the disease.
However, as the authors warn, current diagnostic models are based on studies involving homogeneous populations, which limits their applicability to minority groups or people with different life trajectories. “Diagnostic models must take racial, cultural, and structural diversity into account if we want to move toward truly equitable precision medicine,” explains Dr. Santos-Santos.
The researchers propose an alternative approach based on multifactorial risk prediction models that integrate biological data, neuropsychological testing, and social determinants of health. These models would better identify those individuals who would truly benefit from monitoring or early intervention strategies, avoiding unnecessary diagnostic labeling.
In addition, the commentary emphasizes the importance of clearly and responsibly communicating biomarker findings to patients, to avoid misunderstandings and negative impacts on their psychological well-being. In this regard, the authors advocate for an interdisciplinary approach that combines scientific evidence with each individual’s personal context.
This work reinforces the commitment of IR Sant Pau and the Memory Unit at Hospital de Sant Pau to cutting-edge international research in brain aging and dementias. Their contribution to the global debate on how to ethically, equitably, and effectively use the diagnostic tools of the future.
Reference article:
Grasso SM, Santos-Santos MÁ, Clark AL. On the complexity of biomarker-driven diagnoses of Alzheimer’s disease. J Neuropsychol 2025. https://doi.org/10.1111/jnp.12428
