Palmqvist S, Tideman P, Mattsson-Carlgren N, Schindler SE, Smith R, Ossenkoppele R, Calling S, West T, Monane M, Verghese PB, Braunstein JB, Blennow K, Janelidze S, Stomrud E, Salvadó G, Hansson O. Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care. JAMA. 2024 Oct 15;332(15):1245-1257. PubMed.
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University of California, San Diego
This study combines data from a group of primary care practices and from the BioFINDER study to analyze the value of plasma %p-tau217 (measured as part of the C2N Precivity2 assay and compared against the p-tau217 percentage occupancy alone) in improving diagnostic accuracy, with a prespecified single cutoff, or range of cutoffs, that optimized sensitivity and specificity at the expense of a “gray area” of indeterminate results. Plasma %p-tau217 showed great promise in both settings. The results are highly informative and promising for demonstrating feasibility and utility of plasma %p-tau217 as an aid to AD diagnosis.
The characteristics of patients who had clinical screening/assessment and then biomarker evaluation were remarkably similar in primary care and in the BioFINDER secondary care cohort, including age, sex and APOE e4 genotype. The last of these may have been an important aspect that contributed to the high diagnostic accuracy/predictive value in the primary care cohorts. There is a higher prevalence of APOE4 in Northern European countries than elsewhere, and it would be interesting to see comparable studies from countries or populations where APOE4 is less common. The primary care cohorts had higher rates of comorbidity than the secondary clinic cohort, which is more representative of a general population.
The accuracy of the primary care clinicians’ suspicion of AD was only 58% compared to %p-tau217, therefore the blood-based biomarker could make a difference to clinical judgment and have an impact on appropriateness of referrals. It would be interesting to know how (and whether) the primary care physicians diagnosed the categories of subjective cognitive decline, MCI or dementia, and what additional history or data may have been available besides the MMSE.
Also, the percentage of patients with SCD, MCI, and AD in primary care who were biomarker positive were not reported. Methods of initial history and cognitive screening could have an impact on how often a primary care physician might order a screening blood test, and the PPV will be lower if it is ordered in populations with lower prevalence APOE e4 or among people with low pretest likelihood of having AD. There may be room for improvement beyond the MMSE as a screening test in primary care, to increase the accuracy of pretest suspicion of AD.
It will be interesting to see further studies of how primary, and secondary, care clinics use and interpret blood-based biomarkers, especially in populations with diverse ethnic populations and among older patients, where multi-etiology dementia is common. How results are communicated to patients and whether blood tests can serve as stand-alone biomarkers that may rule a patient in or out as a candidate to receive therapy, will require further study. The present study makes important advances in addressing some of these questions.
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