A new lexicon that revises and unifies the definition of Alzheimer’s disease (AD) to include recent developments in the field, in which biomarkers are the key to diagnosis, has been proposed by an international group of Alzheimer’s disease experts. The wide range of diagnoses identify AD at a far earlier stage and could help select more patients for trials of disease-modifying drugs appropriate to their specific phase of the disease course, according to a Position Paper published Online First and in the November edition of The Lancet Neurology.
In 2007, the International Working Group for New Research Criteria for the Diagnosis of AD proposed a new diagnostic framework to improve the early, accurate diagnosis of AD during a patient’s life based on a specific pattern of cognitive changes and biological features.
In this Position Paper, the same group led by Bruno Dubois from the Salpêtrière Hospital, Paris, France, redefine AD as a clinical-biological syndrome enabling diagnosis to be made much earlier. Instead of requiring a post-mortem examination to certify AD, a diagnosis can now be confirmed on the basis of biomarkers that can be easily identified in living patients even at an early stage in the disease course.
According to the authors, contrary to the traditional approach of diagnosing AD, the presence of full-blown dementia is no longer required. To meet the criteria for a diagnosis of AD, patients must have episodic memory impairment (eg, difficulty in learning a list of words even with cueing) plus the presence of biological evidence (at least one positive biomarker) shown on MRI, neuroimaging with PET, or cerebrospinal fluid (CSF) analysis. As such, patients are identified with a high level of accuracy at a much earlier stage when clinical symptoms first appear.
The authors point out that the simplicity of the proposed criteria has the major advantage “that there is no longer a reason to wait until patients have developed full-blown dementia or to exclude from diagnosis and treatment a large number of patients who lack functional disability yet express the disease”.
They say: “The value of these definitions is their potential application in clinical trials of disease-modifying drugs. Individuals identified as ‘asymptomatic at risk for AD’ or ‘presymptomatic AD’ might be enrolled in trials aimed at delaying onset of clinical signs. Patients with prodromal AD [predementia stage of AD] could be included in trials of drugs targeting progression to more severe stages of AD. Uniformity of definitions will assist in constructing trial populations and comparing results across trials.”
In a Comment, Lon Schneider from the University of Southern California Keck School of Medicine and the University of Southern California Alzheimer’s Disease Research Center in Los Angeles says: “The simplicity of these criteria will be appealing to clinical trialists because they provide a broad range of diagnoses for Alzheimer’s disease that can potentially be included in product labelling…A combination of biomarker level and clinical expression might be used to select patients who are transitioning through a specific phase that is hypothesised to be favourable to a drug being tested.”
However he cautions: “Although this lexicon is well integrated and conceptually attractive, field trials are needed to establish whether the diagnostic criteria will work effectively in clinical or research situations.”
Date: October 10, 2010