Table 2.
Comparison among fluid biomarkers on predicting Aβ positivity in cognitively impaired BioFINDER-2 patients with in-bag estimates
| Single-cutoff approach | ||||||||
|---|---|---|---|---|---|---|---|---|
| Accuracy | PPV | NPV | Sensitivity | |||||
| Mean | Difference | Mean | Difference | Mean | Difference | Mean | Difference | |
| Plasma %p-tau217 | 0.90 (0.86, 0.93) | Ref. | 0.91 (0.88, 0.93) | Ref. | 0.89 (0.81, 0.96) | Ref. | 0.89 (0.80, 0.96) | Ref. |
| CSF p-tau/Aβ42 | 0.91 (0.86, 0.94) | −0.01 (−0.06, 0.05) | 0.91 (0.88, 0.93) | 0.00 (−0.02, 0.02) | 0.91 (0.82, 0.97) | −0.02 (−0.10, 0.08) | 0.91 (0.81, 0.97) | −0.02 (−0.12, 0.10) |
| CSF Aβ42/40 | 0.87 (0.77, 0.93) | 0.03 (−0.04, 0.13) | 0.90 (0.87, 0.93) | 0.01 (−0.02, 0.04) | 0.85 (0.71, 0.96) | 0.04 (−0.08, 0.19) | 0.83 (0.64, 0.96) | 0.05 (−0.09, 0.26) |
| Two-cutoffs approach | ||||||||
|---|---|---|---|---|---|---|---|---|
| Accuracy | PPV | NPV | Number of intermediate participants | |||||
| Mean | Difference | Mean | Difference | Mean | Difference | Mean | Difference* | |
| Plasma %p-tau217 | 0.95 (0.94, 0.97) | Ref. | 0.95 (0.94, 0.97) | Ref. | 0.96 (0.94, 0.98) | Ref. | 16.3 (5.9, 25.3) | Ref. |
| CSF p-tau/Aβ42 | 0.95 (0.94, 0.96) | 0.00 (−0.01, 0.02) | 0.94 (0.91, 0.96) | 0.01 (−0.02, 0.04) | 0.95 (0.95, 0.97) | 0.00 (−0.02, 0.03) | 16.5 (4.6, 33.6) | 0.00 (−0.13, 0.18) |
| CSF Aβ42/40 | 0.94 (0.93, 0.96) | 0.01 (−0.01, 0.03) | 0.93 (0.88, 0.95) | 0.03 (−0.01, 0.08) | 0.95 (0.95, 0.97) | 0.00 (−0.02, 0.02) | 25.4 (8.9, 42.1) | 0.09 (−0.07, 0.27) |
Comparison estimates among fluid biomarkers on predicting Aβ PET positivity in BioFINDER-2 cognitively impaired individuals. For the single-cutoff approach, cutoffs of fluid biomarkers were derived by maximizing sensitivity and fixing specificity at 90% against each imaging outcome. For the two-cutoffs approach, the lower cutoff was obtained by maximizing specificity with sensitivity fixed at 95%, whereas the upper cutoff was obtained by maximizing sensitivity and fixing specificity at 95%. Participants who fall between these two cutoffs were classified in the intermediate group. Differences between the statistics using plasma %p-tau217 (reference) and CSF biomarkers are shown together with the mean values. We considered plasma and CSF biomarkers clinically equivalent if the 95% CI of the mean difference included zero and clinically superior if it did not include zero and favored plasma (>0). *Differences in the number of participants in the intermediate group were scaled to a maximum of 1 to be comparable with the other differences. Aβ PET positivity was assessed as Centiloids ≥ 37. CSF, cerebrospinal fluid; NPV, negative predictive value; PPV, positive predictive value; CI, confidence interval.