Blood test delivers precision to AD diagnosis in primary, secondary care

A blood test for identifying Alzheimer’s disease (AD) among individuals with cognitive symptoms appears to be highly accurate, outperforming traditional methods used in the primary and secondary care settings, according to a study.

Called PrecivityAD2, the blood test combines the ratio of plasma phosphorylated tau 217 (p-tau217) relative to non-p-tau217 (expressed as percentage of p-tau217) and the ratio of plasma amyloid-β42 and amyloid-β40 (Aβ42:Aβ40), analysed by mass spectrometry. The test generates the amyloid probability score 2 (APS2).

Based on plasma samples sent for analysis within 2 weeks of collection, APS2 had an accuracy of 91 percent for detecting AD pathology in patients with mild cognitive impairment or mild dementia. This performance surpassed that of dementia specialists and primary care physicians who achieved 73 percent and 61 percent accuracy, respectively, after a standard clinical evaluation that did not include collection of biomarker data (ie, a full clinical evaluation plus cerebrospinal fluid (CSF) test and/or PET imaging). [JAMA 2024;doi:10.1001/jama.2024.13855]

“This really shows the huge potential of introducing this type of blood test definitely in primary care but also in secondary care if you do not have access to CSF or PET imaging,” said senior author Dr Oskar Hansson of Clinical Memory Research Unit, Department of Clinical Sciences, Lund University in Lund, Sweden, who presented the findings at AAIC 2024.

“But in centres with CSF and PET imaging, [the blood test] can replace [those diagnostic methods] for many patients, [especially] if you’re primarily interested in AD pathology and not other types of brain diseases,” Hansson added.

Study details

The study included 1,213 patients (mean age 74.2 years, 48 percent women) undergoing clinical evaluation due to cognitive symptoms, of which 515 and 698 were recruited from primary and secondary care clinics, respectively. Overall, 23 percent of patients had subjective cognitive decline, 44 percent had mild cognitive impairment, and 33 percent had dementia.

One plasma sample from each of the 307 patients in the primary care cohort and 300 of those in the secondary care cohort was analysed as part of a single batch. Likewise, one plasma sample for each of the 208 and 398 patients in the respective cohorts was sent for analysis within 2 weeks of collection and evaluated prospectively.

Compared with those in the secondary care cohort, patients in the primary care cohort were older (median age 77.3 vs 74.1 years), had less advanced cognitive impairment (subjective cognitive decline: 27.2 percent vs 19.9 percent; dementia: 28.0 percent vs 36.5 percent), and were more likely to have comorbidities (cardiovascular disease: 69.5 percent vs 48.7 percent; chronic kidney disease: 26.2 percent vs 16.9 percent; diabetes: 22.1 percent vs 14.9 percent).

The primary outcome was AD pathology, determined by abnormal CSF amyloid ratios and p-tau217. In both the primary care and secondary care assessments, 50 percent of patients had AD pathology.

When the plasma samples were analysed in a single batch, APS2 had an area under the curve (AUC) of 0.97, positive predictive value (PPV) of 91 percent, and negative predictive value (NPV) of 92 percent for detecting AD pathology in the primary care cohort. The corresponding values in the secondary care cohort were 0.96, 88 percent, and 87 percent.

Results were consistent when the plasma samples were analysed prospectively. APS2 had an AUC of 0.96, PPV of 88 percent, and NPV of 90 percent for detecting AD pathology in the primary care cohort. In the secondary care cohort, the AUC was 0.97, the PPV was 91 percent, and the NPV was 91 percent.

The diagnostic accuracy of APS2 was high across the four cohorts, with a range of 88 percent to 92 percent. Furthermore, in the overall population, the diagnostic accuracy for AD pathology using the APS2 (90 percent) was comparable to the diagnostic accuracy using the percentage of p-tau217 alone (90 percent).

In a news release, lead author Dr Sebastian Palmqvist from the Lund University commented that the results of the study were especially impressive, “considering that older populations in primary care often have medical conditions that can influence or vary the concentrations of p-tau217.”

“We see this as a major step towards global clinical implementation of an Alzheimer’s blood test. 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,” Hansson said.