Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.
On July 29, 2024, we reported on findings from a study published in JAMA that examined the diagnostic accuracy of an Alzheimer disease (AD) blood test when applied with predefined cutoff values in both primary and secondary care settings.
The study
The PrecivityAD2 blood test algorithm incorporated the ratio of plasma phosphorylated tau 217 (p-tau217) relative to non-p-tau217 (expressed as %p-tau217 in the study), combined with the amyloid-β 42 and amyloid-β 40 (Aβ42:Aβ40) plasma ratio (referred to as the amyloid probability score 2 [APS2]), based on mass spectrometry assays. Investigators compared the blood tests’ accuracy with physician diagnoses based on standard evaluations that included clinical exams, cognitive tests, and a CT scan.
The cohort consisted of participants in the Swedish BioFINDER and BioFINDER2 trials who had clinical evaluations due to cognitive symptoms from February 2020 through January 2024. The mean age was 74.2 years, and 48% of participants were women, 23% had subjective cognitive decline, 44% had mild cognitive impairment, and 33% had dementia. In both the primary and secondary care assessments, 50% of patients had AD pathology.
One plasma sample from each patient was analyzed as part of a single batch for each cohort. The blood test also was evaluated prospectively in each cohort, with one plasma sample per patient sent for analysis within 2 weeks of collection. The primary outcome was AD pathology—determined by abnormal cerebrospinal fluid Aβ42:Aβ40 plasma ratio and p-tau217—and the secondary outcome was clinical AD. Researchers calculated predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and area under the curve (AUC) values.
The findings
When researchers analyzed plasma samples in a single batch in the primary care cohort, the blood test showed an AUC of 0.97 (95% CI 0.95-0.99), PPV of 91% (95% CI 87%-96%), and NPV of 92% (95% CI 87%-96%). In the secondary care cohort, when the blood test was used, AUC was 0.96 (95% CI 0.94-0.98), PPV was 88% (95% CI 83%-93%), and NPV was 87% (95% CI 82%-93%).
When the plasma samples were examined prospectively (biweekly) in the primary care cohort, the blood test had an AUC of 0.96 (95% CI 0.94-0.98), PPV of 88% (95% CI 81%-94%), and NPV of 90% (95% CI 84%-96%); in the secondary care cohort, the AUC was 0.97 (95% CI 0.95-0.98), the PPV was 91% (95% CI 87%-95%), and the NPV was 91% (95% CI 87%-95%).
Investigators also reported that the blood test showed high accuracy using predefined cutoff values, ranging from 88% to 92% across all 4 cohorts. In the overall population, the diagnostic accuracy of the blood test (90%, 95% CI 88%-92%) was the same as the diagnostic accuracy using the %p-tau217 alone (90%, 95% CI 88%-91%).
Authors' comment
"We see this as a major step towards global clinical implementation of an Alzheimer’s blood test. It highlights the need for Alzheimer’s biomarkers in making a correct diagnosis more of the time. The next steps include establishing clear guidelines for how an Alzheimer’s blood test can be used in clinical practice, preferably by implementing these tests first in specialist care and then in primary care. This work is currently ongoing."
