Alzheimer's: New strategy for amyloid diagnostics

They will soon be approved in Germany: the first drugs to slow down the progression of Alzheimer's disease. On November 14, 2024, the EMA approved the approval of lecanemab in the European Union. These drugs target the so-called amyloid deposits in the brain. The question is: how can the presence of amyloid deposits be reliably and cost-effectively detected in patients who present to the memory clinic with mild cognitive impairment or mild dementia? In other words, the target group for the medication.

A new study by doctors at the LMU Hospital provides answers that could be used in the treatment of patients. It was initiated by Professor Matthias Brendel, Acting Director of the Department of Nuclear Medicine, Dr. Nicolai Franzmeier from the Institute for Stroke and Dementia Research and Professor Günter Höglinger, Director of the Department of Neurology - they are also members of the SyNergy Cluster of Excellence. The results have now been published in the Journal of the Alzheimer's Society, Alzheimer's and Dementia - Diagnosis, Assessment & Disease Monitoring.

Which method is better?

There are basically two approved methods for detecting the dangerous amyloid deposits in the brains of Alzheimer's patients. Method number 1: the examination of cerebrospinal fluid (“nerve water”). The problem: this puncture of the spinal canal with a cannula is an invasive procedure with rare complications. And for some patients - for example those taking blood-thinning medication - this examination is not suitable. In addition, CSF analysis is an indirect, non-quantitative detection of amyloid deposits in the brain.

Method number 2: a special brain imaging procedure, PET (positron emission tomography). This method enables the direct and semi-quantitative detection of amyloid deposits in the brain and is non-invasive. However, at 1,500 to 3,000 euros per examination, the procedure is still quite expensive and is currently not reimbursed by health insurance companies, meaning that access to it is not yet possible everywhere. Depending on the equipment and expertise of the centers, amyloid imaging and cerebrospinal fluid analysis are also used in different ways in Germany, with cerebrospinal fluid analysis currently being more widely used.

In order to find out how meaningful the results of the CSF examination are in relation to the gold standard PET imaging, the Munich researchers analyzed data from over 400 patients with suspected Alzheimer's dementia who had undergone both a CSF examination for amyloid and a PET of the brain at the LMU Hospital between 2013 and 2024.

The results: Those who had an amyloid value of over 7.1 in the cerebrospinal fluid were mostly unremarkable in the PET - Alzheimer's findings were therefore negative. Patients with an amyloid value of less than 5.5 in the cerebrospinal fluid were also predominantly conspicuous in the PET - Alzheimer's findings were therefore most likely positive. However, it is particularly important that there was a gray area between 5.5 and 7.1 in the cerebrospinal fluid - in around 15 to 20 percent of patients. “Half of these study participants had an abnormal amyloid finding in the PET,” says Brendel, ”so the cerebrospinal fluid examination is not reliable enough here.” The researchers achieved exactly the same result in an independent patient cohort at the University of Vienna. These are therefore robust results.

Possible consequences for practice

As soon as the new drugs against amyloid deposits are approved, the findings of the study could be used in diagnostics. Where it is established, amyloid PET would be the diagnostic method of choice. However, depending on the expertise and equipment at the location, many patients in Germany will have access to CSF analysis rather than amyloid PET in the current situation. “From a medical and economic point of view, it seems justifiable to carry out a cerebrospinal fluid analysis in these patients to select a therapy, provided there are no medical reasons not to do so,” says Brendel.

This applies to around 70 to 80 percent of patients. “Of these patients, only those who are in the gray zone between 5.5 and 7.1 in the CSF examination would then require an additional PET examination.” Matthias Brendel: “Especially if the costs of amyloid PET fall in the future and broader access becomes possible, amyloid PET as the first choice could avoid the effort and costs of duplicate examinations - CSF and PET - which are otherwise sometimes necessary.”

Matthias Brendel, Tandis Parvizi, Johannes Gnörich et al.: β-Amyloid Status Assessment in a Hypothetical Scenario Prior to Treatment with Disease Modifying Therapies: Evidence from 10-Year Real-World Experience at University Memory Clinics. Alzheimer's & Dementia 2024