PT  - JOURNAL ARTICLE
AU  - Gogola, Alexandra
AU  - Lopresti, Brian J.
AU  - Tudorascu, Dana
AU  - Snitz, Beth
AU  - Minhas, Davneet
AU  - Doré, Vincent
AU  - Ikonomovic, Milos D.
AU  - Shaaban, C. Elizabeth
AU  - Matan, Cristy
AU  - Bourgeat, Pierrick
AU  - Mason, N. Scott
AU  - Aizenstein, Howard
AU  - Mathis, Chester A.
AU  - Klunk, William E.
AU  - Rowe, Christopher C.
AU  - Lopez, Oscar L.
AU  - Cohen, Ann D.
AU  - Villemagne, Victor L.
AU - for the Alzheimer’s Disease Neuroimaging Initiative
TI  - Biostatistical Estimation of Tau Threshold Hallmarks (BETTH) Algorithm for Human Tau PET Imaging Studies
AID  - 10.2967/jnumed.123.265941
DP  - 2023 Nov 01
TA  - Journal of Nuclear Medicine
PG  - 1798--1805
VI  - 64
IP  - 11
4099  - http://jnm.snmjournals.org/content/64/11/1798.short
4100  - http://jnm.snmjournals.org/content/64/11/1798.full
SO  - J Nucl Med2023 Nov 01; 64
AB  - A methodology for determining tau PET thresholds is needed to confidently detect early tau deposition. We compared multiple threshold-determining methods in participants who underwent either 18F-flortaucipir or 18F-MK-6240 PET scans. Methods: 18F-flortaucipir (n = 798) and 18F-MK-6240 (n = 216) scans were processed and sampled to obtain regional SUV ratios. Subsamples of the cohorts were based on participant diagnosis, age, amyloid-β status (positive or negative), and neurodegeneration status (positive or negative), creating older-adult (age ≥ 55 y) cognitively unimpaired (amyloid-β–negative, neurodegeneration-negative) and cognitively impaired (mild cognitive impairment/Alzheimer disease, amyloid-β–positive, neurodegeneration-positive) groups, and then were further subsampled via matching to reduce significant differences in diagnostic prevalence, age, and Mini-Mental State Examination score. We used the biostatistical estimation of tau threshold hallmarks (BETTH) algorithm to determine sensitivity and specificity in 6 composite regions. Results: Parametric double receiver operating characteristic analysis yielded the greatest joint sensitivity in 5 of the 6 regions, whereas hierarchic clustering, gaussian mixture modeling, and k-means clustering all yielded perfect joint specificity (2.00) in all regions. Conclusion: When 18F-flortaucipir and 18F-MK-6240 are used, Alzheimer disease–related tau status is best assessed using 2 thresholds, a sensitivity one based on parametric double receiver operating characteristic analysis and a specificity one based on gaussian mixture modeling, delimiting an uncertainty zone indicating participants who may require further evaluation.