Biomarkers

Recent global breakthroughs have enabled blood-tests to detect key proteins implicated in the pathophysiology of Alzheimer's disease (AD). Clinical implementation of a non-invasive, cost-effective blood-test could improve diagnostic accuracy, particularly in the early stages of the disease, facilitating timely commencement of disease-modifying therapies. In this study, we evaluated the impact of disclosing a patient's AD probability, determined by plasma pTau181 levels, on clinicians' diagnostic confidence and management.

We conducted a before-and-after study in three Australian Memory and Cognition Clinics, enrolling routine patients aged ≥50 years and MMSE scores ≥23. Blood was collected at initial assessment, followed by a multidisciplinary evaluation to determine diagnosis, management, and clinician confidence prior to receiving blood-test results. Plasma pTau181 levels were measured on the Quanterix Simoa™ platform; and results were reported to clinicians as probably negative, indeterminate or probably positive, based on two thresholds set at 90% sensitivity and 90% specificity for amyloid-beta PET positivity. The impact of the blood-test result on the initial diagnosis, management and confidence was documented after clinicians reviewed the report.

A total of 113 participants (mean age: 73.6±7.8; mean MMSE: 27.7±2.5) with dementia (n = 17, 15.0%), mild cognitive impairment (n = 48, 42.5%) and subjective cognitive decline (n = 48, 42.5%) were enrolled. Mean diagnostic confidence following initial clinical assessment was moderate-to-high (77.2%). Most blood-test results received were probably negative (n = 81, 71.7%), followed by indeterminate (n = 24, 21.2%) and probably positive (n = 8, 7.1%). In 14 cases (12.4%), blood-test results (probably negative: n = 8; probably positive: n = 3; indeterminate: n = 3) changed clinician diagnosis, increasing mean diagnostic confidence in these patients from low-to-moderate (63.1%) to moderate-to-high (78.6%), with a mean increase of 15.4%. Two-thirds of clinicians would recommend the clinical use of such blood-tests with further refinement.

This study highlights the potential of a blood test for AD in clinical practice, enhancing diagnostic accuracy in cases with low-to-moderate diagnostic confidence.