Jul 7, 2014

30 Percent of Alzheimer's Patients are Misdiagnosed

How many patients receive an incorrect diagnosis of Alzheimer's disease? Over 30 percent!

Bob DeMarco
Alzheimer's Reading Room

30 Percent of Alzheimer's Patients are Misdiagnosed

Many people were surpised when I didn't have my mother's grain autopsied after her death. They asked, don't you want to know for sure that it was Alzheimer's?

My answer was simple and straightforward - No. I know what I saw, and I know how we lived, nothing was going to change those facts.

However, many loved one's of people living with dementia do want an autopsy. The reason is simple, a large fraction of people diagnosed with dementia are misdiagnosed. And many people, just want to know.

If this is an issue for you, or a potential issue, you should find the research summary presented below of great interest.
  • Alzheimer's disease is a neurodegenerative disease. It is the most common (70%) form of dementia.
  • In the early stages of this study it was determined that "36% of  patients included in a therapeutic trial based on previous clinical criteria did not have Alzheimer's disease". 
  • As a result, patients did not receive the correct treatment and/or care.
  • Most of the time, the diagnosis of Alzheimer's disease is based primarily on a suggestive clinical picture.

Subscribe to the Alzheimer's Reading Room
Email:

Alzheimer's disease: Simplified diagnosis, with more reliable criteria

The Gist
  • To reduce the number of errors, the diagnostic criteria must be the most reliable possible, especially at the very early stages of the disease. 
  • In the June issue of The Lancet Neurology  journal, we learn how researchers developed a simplified diagnosis based on the most specific criteria of the disease. A challenge not only for research, but also for clinical practice.
Alzheimer's disease is a neurodegenerative disease. It is the most common (70%) form of dementia. 
  • Alzheimer's disease results from a loss of neurons. 
  • The lesions are caused by an accumulation of some brain proteins. 
  • The pathology begins with memory problems
  • This is followed by problems of orientation in space and in time, behavioural problems and loss of autonomy. 
However, these symptoms are not specific to Alzheimer's disease.
  • The real challenge is to know how to distinguish Alzheimer's disease from other types of dementia, and establish the diagnosis as reliably and as early as possible.
In 2005, an international group of neurologists, coordinated by Bruno Dubois at Inserm, came together to redefine the diagnostic criteria established in 1984. Until then, it had been necessary to await the death of a patient in order to establish a diagnosis of Alzheimer's disease with certainty by examining the lesions in his/her brain.

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.

The Findings
  • In 2007, the international team shattered these concepts. The researchers introduced new diagnostic criteria, particularly biomarkers. These are genuine signatures of the disease, and are present from the initial symptoms (prodromal stage).
  • The publication of these results constituted a revolution. 
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". 

As a result, patients did not receive the correct treatment and/or care.

And 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. And the international group decided to analyse this literature to make the diagnostic algorithm for Alzheimer's disease 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", indicates 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 Alzheimer's disease 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:
  • 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)
  • 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 behavioural problems)
  • 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:
  • in the cerebrospinal fluid (obtained by lumbar puncture): abnormal levels of brain proteins (reduced beta amyloid protein and increased tau protein)
  • in the brain by PET (positron emission tomography) neuroimaging: elevated retention of amyloid tracer
This simpler and more reliable algorithm is important, primarily for research (therapeutic trials, characterisation of the disease, monitoring of patient cohorts, etc.).

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 expert centers.
____________________________________

Sources

Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria Bruno Dubois et al.

The Lancet Neurology, vol.13,  June 2014

Related Articles


Original content Bob DeMarco, the Alzheimer's Reading Room