The new blood test for Alzheimer’s disease: developed in a study without patients

Cecile Janssens

“Blood test is highly accurate at identifying Alzheimer’s before symptoms arise. When combined with age and genetic risk factor, test is 94% accurate.”

“Up to two decades before people develop the characteristic memory loss and confusion of Alzheimer’s disease, damaging clumps of protein start to build up in their brains. Now, a blood test to detect such early brain changes has moved one step closer to clinical use.”

It is these opening lines of the study’s press release that shaped the news. The Alzheimer’s Society reports that “Blood test is 94 per cent accurate at identifying early Alzheimer’s disease”; The Guardian that “Alzheimer’s blood test could predict onset up to 20 years in advance”; and also the doctors at WebMD highlight that “Blood test may spot signs of early Alzheimer’s.”

But no, the study didn’t test and track people for 20 years to see who ultimately developed Alzheimer’s disease. And the test wasn’t 94 per cent accurate in identifying early Alzheimer’s either. None of the participants in the study was diagnosed with Alzheimer’s disease. Their average score on the Mini Mental State Examination, a well-known test to measure cognitive impairment, was 29. As a reference: the test’s best possible score is 30, a score of 20 to 24 may indicate mild dementia, and lower than 12 severe dementia.

The study wasn’t about prediction either. The claim that indications of brain amyloidosis can be observed two decades before the first symptoms appear must have come from other studies. I didn’t find citations to these studies in the article. (I wonder whether such prediction studies exist.)

The researchers aimed to find a simple alternative for the measurement of the Aβ42/Aβ40 ratio, which is an indicator for brain amyloidosis, the plaques that are frequently found in Alzheimer patients (see Figure). This ratio can be calculated from a lumbar puncture or a PET scan, both of which are costly and may have side effects. A blood test would be a simple, inexpensive alternative.

Outline of the study and its (distant) relation to Alzheimer’s disease.

What the researchers did in this study was correlating the results of a blood test, lumbar puncture and PET scan in a small sample of 158 participants. They performed many analyses, and one of them showed that a composite test based on the Aβ42/Aβ40 ratio, APOE*4 (DNA) status, and age was 94% accurate in identifying participants with a ‘positive’ PET scan. What’s crucial here: ‘positive’ was not defined according to an objective agreed-upon threshold for early screening of Alzheimer’s disease; it was based on a threshold that was optimal for distinguishing between higher and lower PET scan scores in this small and cognitively healthy study population. Whether the higher PET scan scores, and thus the blood test results, in this population are ‘abnormal’ enough to predict future Alzheimer’s disease is unknown.

It may well be that plaques can be found in patients with Alzheimer’s disease decades before their first symptoms, but they are also found in people who have no cognitive impairment and may never develop dementia. A ‘positive’ blood test may increase the risk of Alzheimer’s, the question is by how much.

This is not the first study that showed promising results for a blood test for Alzheimer’s disease. Last year, a team of Japanese and Australian researchers observed 90% accuracy for their blood test and were reported to have found “New Blood Test For Alzheimer’s Is So Precise It Could Predict It 30 Years Ahead.”

A blood test for Alzheimer’s may be “one step closer,” but still is miles away. It is not a test for Alzheimer’s if it can’t predict future disease. Let’s get that evidence first.

Cecile Janssens

Written by

Professor of epidemiology | Emory University, Atlanta USA | Writes about (genetic) prediction, critical thinking, evidence, and lack thereof.

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