By Lucy Piper, medwireNews reporter
medwireNews: The use of blood-based biomarkers could improve the process for identifying individuals suitable for Alzheimer’s disease (AD) treatment, delegates at the Alzheimer’s Association International Conference 2024 were told.
Presenting the findings in Philadelphia, Pennsylvania, USA, Sinthujah Vigneswaran (Vrije Universiteit Amsterdam, the Netherlands) said that including blood-based biomarker measurement at various stages in a standard diagnostic workflow could “increase efficiency of the triage process and reduce costs of the ancillary investigations.”
The researchers assessed the potential benefit of incorporating the measurement of a blood-based biomarker panel at different stages of a standard workflow to determine a patient’s eligibility for disease-modifying treatment for Alzheimer’s disease (AD), based on the appropriate use criteria for lecanemab.
In all, 997 participants of the Amsterdam Dementia Cohort who had cognitive complaints were medically assessed. Of these, 373 had a score of 0.5–1.0 points on the Clinical Dementia Rating scale and a Mini Mental State Examination score of 22–27 points and were therefore eligible for a magnetic resonance imaging (MRI) brain scan. This showed that 268 of the patients had fewer than 4 microhemorrhages and so they underwent tests to determine amyloid status – cerebrospinal fluid (CSF) phosphorylated (p)-tau181/amyloid-β42 or positron emission tomography (PET) amyloid – 183 of whom were positive and therefore eligible for anti-amyloid treatment.
Using the Youden’s Index cutoff of 95% specificity to distinguish those with and without amyloid positivity, measuring p-tau217 identified amyloid-positive patients with a specificity of 87% and a sensitivity of 86%. The false negative rate, where patients tested negative on the blood test but were identified as positive on CSF/amyloid PET, was 32%, while the false positive rate, where patients tested positive on the blood test but negative on CSF/amyloid PET, was 7%.
Vigneswaran highlighted that in the scenario where p-tau217 testing was done after brain MRI, it would have reduced the need for CSF/amyloid PET tests by 49%. If done after medical examination, it would have reduced the need for MRI by 47% as well as the 49% fewer CSF/amyloid PET tests and if done on entry to the memory clinic before medical examination, it would have meant a total of 43% fewer medical consultations, 47% fewer brain MRIs, and 49% fewer CSF/amyloid PET tests.
She said that this model fits “with a conservative treatment approach, because the false positive rate is low that means you accept undertreatment of patients.”
The team also looked at the same process but using a low-intermediate-high stratification model using a cutoff for low stratification of 90% sensitivity and a 90% specificity cutoff for high stratification with patients between these in an intermediate risk group who would need to undergo CSF/amyloid PET testing anyway. Using this model, the p-tau217 results gave a false negative rate of 5%, a false positive rate of 24%, and in the intermediate group 71% were amyloid positive on CSF/amyloid PET and 29% were amyloid negative.
In this scenario, measuring the blood-based biomarker reduced CSF/amyloid PET, brain MRIs, and medical consultations by a respective 45%, 43%, and 39% when used at the different stages in the process.
The presenter said that this scenario is less cost-saving than the one using the Youden’s Index as a cutoff and “fits more with a treatment regime where a greater number of potentially eligible individuals undergo PET or CSF testing, because there is a higher false positive difference.”
Given the findings, she concluded that “dichotomous stratification, such as the Youden’s Index, may be better suited for plasma p-tau217.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
AAIC24; Philadelphia, Pennsylvania, USA: July 28–Aug 1
