Data‐driven cut‐off values for 18‐F‐AV‐45 tau PET staging in AD. (1st February 2022)

• Record Type: Journal Article
• Authors: Quattrini, Giulia; Ferrari, Clarissa; Pievani, Michela; Frisoni, Giovanni B.; Marizzoni, Moira
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.053480
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The identification of unbiased cut‐off for amyloid and tau positivity is fundamental to early AD classification. While cut‐offs for amyloid markers are relatively established, tau markers cut‐off definition is controversial as they are influenced by the reference population. Moreover, several not modifiable risk factors (i.e., Apolipoprotein E ε4 allele [APOE4], age, and sex) may affect tau pathology. The aim of the present study is to define data‐driven cut‐off values for cortical tau staging and to assess the effect of APOE4, age, and sex. Method: Data were derived from the Alzheimer's Disease Neuroimaging Initiative consortium (ADNI). Amyloid‐PET ( 18 ‐F‐AV‐45) standardized uptake value ratio (SUVR) was used to classify subjects as amyloid positive (A + ) or negative (A ‐ ). Tau PET ( 18 ‐F‐AV1451) SUVR, APOE4, age, sex and clinical information were then collected. For 18 ‐F‐AV1451 SUVR, we applied a staging system according to Braak. Data‐driven stage‐specific 18 ‐F‐AV1451 cut‐offs were computed by applying Gaussian mixture model (GMM) to the subsample including A ‐ cognitively normal (CN‐A ‐ ) and AD dementia (AD‐A + ) (n=194). We also investigated the effect of age, APOE4 status, and sex on 18 ‐F‐AV1451 SUVR distribution and cutoff extraction applying the GMM to 18 ‐F‐AV1451 SUVR distribution adjusted for these covariates. Finally, the cut‐offs sensitivity was assessed in preclinical AD (CN‐A + ; n=45), prodromal AD (MCI‐A + ; n=22), and AD‐A + (n=19) subjects. Result: In tau stage regions I–VI, 18 ‐F‐AV1451 cut‐off values for positivity ranged between 1.21‐1.35. The cut‐offs sensitivity increased from CN‐A + to MCI‐A + and AD‐A + in all tau stages regions: from 20% to 64% and 90% for tau stage I‐II, from 16% to 46% to 90% for tau stage III, from 11% to 46and 90% for tau stage IV, from 0% to 18% and 53% for tau stage V, and from 0% for CN‐A + and MCI‐A + to 32% for tau stage VI. A similar sensitivity progressive pattern was detected within each tau stage region. Finally, APOE4, age, and sex significantly impacted 18 ‐F‐AV1451 regional SUVR of each tau stage. Conclusion: Data‐driven 18 ‐F‐AV1451 SUVR cut‐offs for in‐vivo tau staging could be useful to index regional tau deposition. The impact of APOE4, age, and sex should be also considered.