Alzheimer’s disease is the most common form of dementia – a syndrome that affects memory, thinking, behavior and autonomy. Yet getting a reliable, early diagnosis for Alzheimer’s is not easy – more than 1 in 3 patients receive an incorrect diagnosis. Now an international team of researchers that has spent 10 years working towards a simpler, more reliable approach to the diagnosis of Alzheimer’s disease, reveals its proposals in a Position Paper published in the journal The Lancet Neurology.

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According to the World Health Organization, the number of people with dementia is expected to double by 2030 and more than triple by 2050.

According to the World Health Organization, worldwide there were around 36 million people with dementia in 2010, and this number is expected to double by 2030, and more than triple by 2050.

About 70% of dementia cases are Alzheimer’s – a brain-wasting disease caused by loss of brain cells that become damaged when faulty proteins accumulate inside and around them. As the behavioral and cognitive symptoms of Alzheimer’s disease overlap with other forms of dementia, clinicians and researchers are faced with real challenges when it comes to making a reliable differential diagnosis – especially in the early stages.

In 2005, an international group of neurologists redefined a set of diagnostic criteria for identifying patients with Alzheimer’s. Until then, it had been necessary to wait for patients to die before establishing a diagnosis by autopsy. The most that could be done for living patients was to estimate the probability of them having Alzheimer’s, and then only in the late stages of the disease, which was decided based on severity of dementia.

And then in 2007, the group transformed the diagnostic criteria by introducing the idea of biomarkers. For the first time, there was the possibility of diagnosing Alzheimer’s more reliably in living patients using biological disease signatures that are present in the early stages.

When they revealed their new diagnostic criteria they caused a sensation. One group of researchers declared that “36% of their patients included in a therapeutic trial based on previous clinical criteria did not have Alzheimer’s disease,” says Bruno Dubois, a professor of neurology at the French biomedical and public health research institution Inserm, and co-ordinator of the 2007 group.

Prof. Dubois, who is also first author of the new paper, goes on to explain that the implications of such a discovery were serious – patients were not receiving the right care or treatment, and poor selection of participants is likely also to have led to flawed conclusions about treatment effectiveness.

Things have moved on significantly since 2007, causing the group to revisit the diagnostic criteria for Alzheimer’s in the light of new studies. The Position Paper marks “the end of the road,” says Prof. Dubois, who adds: “we have arrived at the essence, something refined, resulting from an international consensus.”

The group has not only arrived at what it believes is a more reliable algorithm for diagnosing Alzheimer’s, but a much simplified one too, that relies on “just a couple of clinical-biological criteria for all stages of the disease,” explains Prof. Dubois.

The method is in two parts: a suggestive clinical picture that can be one of three scenarios (typical, atypical, and preclinical), and a biomarker.

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In 2007, for the first time, there was the possibility of diagnosing Alzheimer’s more reliably in living patients using biological disease signatures that are present in the early stages.

The group suggests most of the time, the diagnosis of Alzheimer’s will be based primarily on a suggestive clinical picture that is then subsequently confirmed or rejected using one of the two biomarkers.

The three scenarios of the suggestive clinical picture are:

  • Typical cases (expected to be 80-85% of cases): brain changes that lead to problems with episodic long-term memory, including difficulty remembering a list of words, even with hints
  • Atypical cases (15-20% of cases), brain changes that cause problems with verbal memory and other behavioral problems
  • Preclinical states, where patients do not appear to have symptoms, but for some reason – for instance from taking part in a trial – are discovered to have biomarkers or gene mutations for Alzheimer’s.

The two biomarkers – only one of which is required to confirm or reject the suggestive clinical picture diagnosis – are:

  • Abnormal levels of brain proteins in cerebrospinal fluid (higher levels of tau and reduced levels of beta amyloid protein). The fluid is obtained by lumbar puncture
  • PET (positron emission tomography) brain scan that shows higher retention of an amyloid tracer.

Meanwhile, Medical News Today recently learned of a new diagnostic tool to help clinicians differentiate between Alzheimer’s disease, frontotemporal dementia and mild cognitive impairment. The software-based tool is a new combination of various methods for the differential diagnosis of Alzheimer’s and the other two conditions, and comprises a Disease State Index that draws from multiple sources such as psychological tests and brain MRI, and a visual counterpart, a Disease State Fingerprint.