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A combination blood test for cognitive decline has a 90 percent accuracy rate in determining whether memory loss is due to Alzheimer’s disease, a new study finds.
By comparison, neurologists and other memory specialists correctly diagnosed Alzheimer’s disease 73 percent of the time. General practitioners were even less successful, with an accuracy rate of just 61 percent, the study found.
One part of the blood test, called plasma phosphorylated tau 217, or p-tau217 for short, is one of several blood biomarkers that scientists are evaluating for use in diagnosing mild cognitive impairment and early-stage Alzheimer’s disease.
The test measures the protein tau 217, which is a strong indicator of amyloid pathology, said study co-author Dr. Sebastian Palmqvist, associate professor and senior consultant neurologist at Lund University in Sweden.
“The increase in p-tau-217 concentrations in the blood is quite significant in Alzheimer’s disease. In the dementia stage, the levels are more than 8 times higher than in older people without Alzheimer’s,” Palmqvist wrote in an email.
A study published in January showed that a similar p-tau217 test could identify high levels of beta-amyloid with 96% accuracy and detect tau with 97% accuracy. The presence of tangles of beta-amyloid and tau in the brain is a hallmark of Alzheimer’s disease.
In the new study, the p-tau217 test was combined with another blood biomarker of Alzheimer’s disease called the 42/40 amyloid ratio, which measures two types of amyloid proteins, another biomarker of Alzheimer’s disease.
The combination of amyloid and tau tests, called the amyloid probability score, was the most predictive.
“We would like to have a blood test that can be “It’s used in a primary care physician’s office and works like a cholesterol test, but for Alzheimer’s disease,” said Dr. Maria Carrillo, chief scientific officer of the Alzheimer’s Association.
“The p-tau217 blood test turns out to be the most specific for Alzheimer’s disease and the one with the most validity. It seems to be the frontrunner,” said Carrillo, who oversees the association’s research initiatives, including the new study.
Once fully validated, the highly accurate blood tests could be “a game changer in terms of how quickly Alzheimer’s trials can move and how the next new drug can be developed,” she said. “We’re in an absolutely transformative time.”
The p-tau217 peptide is unique in that it can only be detected when amyloid plaques are present in the brain, Carrillo said.
“What this means for us scientifically is that when we measure p-tau217, we are measuring neuronal damage caused by tau very early in Alzheimer’s disease, but only when amyloid is already present,” she said.
“You’re not actually measuring amyloid, but the test tells you it’s there, and that was confirmed by an objective positron emission tomography (PET) scan. “Scans can detect amyloid in the brain,” Carrillo said. “It’s a great marker for Alzheimer’s disease: If you don’t have amyloid, you don’t have Alzheimer’s. But if you have high levels of tau in your brain, we know that’s a sign of another type of dementia.”
Tau tangles are implicated in several other neurological diseases such as frontofacial dementia (FTD). In frontofacial dementia, tau tangles attack the frontal lobe of the brain, causing behavioral and emotional changes and loss of executive functions such as planning. Memory loss, if it occurs, occurs much later.
In Alzheimer’s disease, clumps of tau proteins form in the part of the brain that controls memory, but amyloid plaques play a key role. Small clumps of plaques can gather at synapses and interfere with the ability of nerve cells to communicate. Amyloid plaques can also overstimulate the immune system, triggering inflammation that can further damage the brain.
Some of the newer dementia drugs, such as lecanemab and donanemab, target beta-amyloid and may be less effective in people with advanced tau disease, experts say.
Because amyloid deposits can begin to accumulate in the brain decades before symptoms appear, even when a person is in their 30s or 40s, early diagnosis of brain amyloid could be key to lifestyle changes and preventative treatment with medications.
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In the future, blood tests could detect early deposits of amyloid in the brain, allowing people to take preventative measures to reduce their risk of dementia.
The study, published Sunday in the journal JAMA Neurology, followed 1,213 people with an average age of 74 who underwent cognitive assessments at primary and specialty care clinics in Sweden.
Each person’s blood was tested using p-tau217, and the results were combined with blood measurements of amyloid beta 40/42 to develop a final score.
“When you use a combination of the 40-to-42 ratio and p-tau217, it increases the diagnostic accuracy of p-tau217,” said Dr. Richard Isaacson, a preventive neurologist and director of research at the Neurodegenerative Diseases Institute in Florida, who was not involved in the study.
The 90 percent accuracy of the study’s combined blood test was confirmed by a spinal fluid aspiration, which, along with amyloid positron emission tomography (PET) scan, is currently the only scientific gold standard, other than autopsy, for diagnosing Alzheimer’s disease. Both tests are expensive, invasive and not widely available in the United States, experts say.
The blood test results were then compared with the patients’ diagnoses provided by Swedish general practitioners and specialists. The relatively low accuracy rate (61% and 73%) shows how difficult it is for doctors to correctly identify Alzheimer’s pathology with current tools: a brief interview with the patient, a brief cognitive test and a computed tomography (CT) scan of the brain.
“In general, traditional paper-based tests and digital cognitive assessments are not very accurate in specifically identifying Alzheimer’s disease,” said study co-author Dr. Oskar Hansson, professor and senior consultant in neurology at Lund University.
“Many other conditions and diseases can present with similar cognitive symptoms, which can lead to misdiagnosis or missed diagnosis,” Hansson said in an email.
In fact, between 20 and 30 percent of patients seen by specialists are taking medications or have other conditions that can mimic Alzheimer’s, Hansson said. Conditions that can affect cognitive function include vascular dementia, depression, thyroid disease, sleep apnea and even vitamin B12 deficiency.
If these mimics aren’t detected during the initial screening, people without Alzheimer’s disease can clog up specialist waiting lists and appointments for spinal taps and amyloid positron emission tomography (PET) scans, Carrillo said.
By the time someone with true amyloid disease sees a specialist, she added, they may “no longer be eligible for the drugs that we have, and that’s terrible.”
Wait times will only get worse, according to mathematical models based on the aging of the U.S. population. By 2033, if a primary care doctor uses only current cognitive assessments to determine dementia, people will wait an average of nearly six years to find out if they are eligible for new Alzheimer’s treatments, a new study finds. The study was presented Sunday at the Alzheimer’s Association’s 2024 International Conference in Philadelphia.
However, if accurate blood tests are used, waiting times could be reduced to between six and 13 months, the study said, because far fewer people would need to see a specialist or undergo additional testing.
However, don’t expect blood tests for Alzheimer’s to become a commonplace order in your doctor’s office. More research is needed to verify the positive results of the studies, guidelines for use by physicians need to be developed and disseminated, and physicians need to be made aware of all possible nuances, Isaacson said.
“No one is more optimistic about these tests than I am, but blood tests for Alzheimer’s are not completely definitive yet,” he said. “If the test is positive, it still needs to be confirmed by positron emission tomography or spinal tap. If it’s negative, that’s reassuring, but if it’s borderline, we still don’t know what that means.”
In the meantime, research has shown that there are many steps people can take to prevent or slow cognitive decline, including exercising regularly, adopting a Mediterranean-style diet, and treating vascular risk factors such as high blood pressure, high cholesterol, and diabetes.
“Our goal is to use only the highest quality blood tests not only to help diagnose Alzheimer’s disease early, but also to assess response to risk-reducing interventions,” Isaacson said. “This is a very exciting time.”