Can Blood Tests Detect Cognitive Decline in Your 50s and 60s?

Several blood tests for Alzheimer’s biomarkers have hit the market in the last few years as a less invasive alternative to cerebrospinal fluid tests and amyloid PET scans. The blood tests measure protein fragments indicative of beta-amyloid plaques in the brain — toxic protein aggregates that define the disease.

These blood tests were developed for people with existing cognitive impairment, meaning that it isn’t clear what a positive test result means for a healthy person. A recent study published in The Lancet, authored by Dr. Kristine Yaffe, vice chair at UCSF, found that some blood tests might be able to predict subtle cognitive decline in the 50s and 60s. 

In an accompanying editorial other Alzheimer’s experts cautioned that these tests have a high-rate of false positives in younger, healthy individuals and, as a result, these tests “are not suitable for large-scale, untargeted screening” in healthy people. 

Measuring Alzheimer’s biomarkers in midlife

Yaffe and her colleagues analyzed data from 1,350 people with an average age of 61 i as part of a study tracking cardiovascular disease risk factors. They collected blood samples and ran cognitive tests  then repeated the cognitive testing five years later. They measured proteins that are regularly used by clinicians to help diagnose or rule out Alzheimer’s. 

The blood tests measured different combinations of biomarkers. The first, the Aβ42/40 ratio provides a proxy measure of beta-amyloid plaques in the brain. A lower ratio means that there’s less Aβ42 proteins seeping out into the blood since it’s getting stuck in plaques. About 15 percent of participants tested positive using this test.

The next looked at pTau-217, a fragment of the tau protein that also provides a proxy measurement of beta-amyloid plaques in the brain. The buildup of these plaques causes brain cells to release this protein. Research presented at the Alzheimer’s Association International Conference earlier this year suggests it may predict cognitive decline. In this study, 4 percent tested positive based on pTau-217. 

The final measure assessed the ratio of p-tau217/Aβ42, a combination used in Fujirebio’s blood test, which is cleared by the Food and Drug Administration for confirming Alzheimer’s biomarkers in individuals with cognitive decline. 6 percent of participants tested positive on this measure.

While the study suggests some biomarkers might spot certain signs of cognitive decline early, the results were not conclusive, and the authors urged for more research and replication of the findings.

“Detecting the disease early means patients can target modifiable risk factors and maybe seek other care,”Yaffe said in a press release. 

However, Dr. Andy Liu, neurologist, and associate biomarker core lead at the Duke-UNC Alzheimer’s Disease Research Center, who wasn’t involved in the study, told Being Patient that  he wouldn’t change the management of the patients in his clinic just yet from the results of a blood test alone.

Detecting Alzheimer’s before symptoms start

Although the study is promising, it doesn’t prove that blood tests are ready to detect Alzheimer’s before the onset of symptoms. The study crucially does not track whether individuals actually develop the disease, which is meaningful since these blood tests were developed for cognitively impaired individuals and have a high rate of false positives in a healthy population. 

Another study published last year that used blood tests on healthy older individuals found that a positive test was accurate less than half the time at predicting who would develop the disease 10 years later in an older population, yielding many false positives. 

Meanwhile, Liu is still waiting to see if the anti-amyloid trials being conducted in asymptomatic individuals prove effective at slowing the disease before offering these tests to healthy individuals in his practice. “I think eventually we’ll get there,” he said. “We’re not quite there yet.”