Simplified Alzheimer’s Disease Diagnosis Using PET Imaging and More Effective Criteria

According to French investigators, over one-third of patients receive an incorrect diagnosis of Alzheimer’s disease (AD). To reduce the number of errors, the diagnostic criteria available must be the most reliable possible, especially at the very early stages of the disease. For the past 10 years, an international team of neurologists has been working towards this objective. The researchers recently introduced new diagnostic criteria, in particular, biomarkers. These are authentic signatures of the disease, and are present from the first symptoms (prodromal stage).

In the June 2014 issue of the Lancet Neurology journal, Dr. Bruno Dubois, from the National de la Santé et de la Recherche Médicale (Inserm; Paris, France) and Pierre and Marie Curie University (Paris, France) /AP-HP Joint Research Unit 975) and colleagues have developed a simplified diagnosis based on the most specific criteria of the disease, which should have a major impact in clinical practice.

AD is the most common (70%) form of dementia. The real challenge of a definitive diagnosis is to know how to differentiate this disease from other types of dementia, and establish the diagnosis as effectively and as early as possible.

In 2005, an international group of neurologists, coordinated by Inserm’s Dr. Bruno Dubois, came together to redefine the diagnostic criteria established in 1984. Up to then, it had been necessary to await the death of a patient in order to establish a diagnosis of AD with certainty by examining the lesions in his/her brain. And in the living, only a probability of disease could be inferred, and only at a late stage, based on a certain threshold of severity of dementia.

In 2007, the international team broke these hypotheses apart. The researchers introduced new diagnostic criteria, particularly biomarkers. These are authentic signatures of the disease, and are present from the initial symptoms (prodromal stage). The publication of these findings initiated a transformation. Researchers then observed that with these new criteria, “36% of their patients included in a therapeutic trial based on previous clinical criteria did not have Alzheimer’s disease,” reported Prof. Dubois. However, although this analysis involved only a subgroup of patients, the implications are serious. Patients did not receive the correct treatment and/or care. Moreover, flawed patient selection might have had an impact on the lack of efficacy observed for the new treatment.

Since 2007, many studies have been published. The international group decided to analyze this literature to make the diagnostic algorithm for AD simpler and more reliable. “We have reached the end of the road; we have arrived at the essence, something refined, resulting from an international consensus,” indicated Prof. Dubois. The diagnosis of Alzheimer’s disease will henceforth rely on “just a couple of clinical-biological criteria for all stages of the disease.”

Most of the time, the diagnosis of AD is based primarily on a suggestive clinical picture. It is subsequently confirmed or rejected using a biomarker. As regards the clinical picture, there are three scenarios: (1) typical cases (80%–85% of all cases): impairment of episodic long-term memory (known as amnestic syndrome of the hippocampal type and corresponding to difficulty remembering a list a words, even with clues, for example); (2) atypical cases (15%–20% of cases): atrophy of the posterior part of the cerebral cortex or logopenic aphasia (impairment of verbal memory where the patient inverts the syllables of a word when repeating it, for example), or frontal brain damage, which results in behavioral problems; (3) preclinical states: asymptomatic at-risk (patients without symptoms, but who are fortuitously discovered to have positive biomarkers during scientific studies), and presymptomatic (with a genetic mutation).

One of the following two biomarkers is required: (1) in the cerebrospinal fluid (obtained by lumbar puncture) to ascertain abnormal levels of brain proteins (reduced beta amyloid protein and increased tau protein); (2) and in the brain by positron emission tomography (PET) neuroimaging to determine the elevated retention of amyloid tracer.

This simpler and more effective algorithm is important, mainly for research (therapeutic trials, characterization of the disease, monitoring of patient cohorts), according to the investigators. Outside of research, the use of biomarkers, which is expensive and/or invasive, currently remains limited to young patients or difficult or complex cases in specialty centers.

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National de la Santé et de la Recherche Médicale
Pierre and Marie Curie University