Head-to-Head Comparison of Flortaucipir and MK6240 tau-PET to Detect Subtle Objective Cognitive Impairment in Clinically Unimpaired Individuals
- 1McGill University
Abstract
Background and Objectives: Tau-PET is associated with subtle objective cognitive impairment (SOCI) in clinically unimpaired (CU) individuals, but whether the spatial patterns and strengths of these associations differ across tracers remains unclear. We performed a head-to-head comparison of [18F]MK6240 and [18F]flortaucipir to investigate their associations with SOCI in CU individuals. Methods: We cross-sectionally assessed CU participants from the HEAD study who underwent both tau-PET scans. Linear regressions examined associations between domain-specific cognition and tau burden using standardized uptake value ratios (SUVR) in regional and voxelwise analyses, alongside regional spatial extent of tauopathy (SEOT) measures. Tau burden was compared across groups representing different levels of SOCI. Models adjusted for age, sex, and education, with additional adjustment for amyloid-beta burden. Centiloid-stratified analyses examined associations across amyloid-beta burden levels. Results: Among 297 participants (mean [SD] age, 67.0 [8.4] years; 179 [60.3%] female), higher [18F]MK6240 SUVR was associated with poorer memory performance. Greater SEOT with either tracer was associated with poorer memory and showed nominal associations with executive dysfunction. Regional association strengths did not differ significantly between tracers, while SEOT yielded comparable or stronger associations than SUVR. Centiloid-stratified analyses revealed tau-cognition associations primarily at intermediate and high amyloid-beta burden. [18F]MK6240 showed more spatially extensive voxelwise associations with memory and across SOCI group comparisons. Regional analyses also yielded more statistically significant differences across SOCI groups with [18F]MK6240 than with flortaucipir. These differences were predominantly driven by participants meeting actuarial mild cognitive impairment criteria, who exhibited greater tau burden than groups with less pronounced psychometric impairment. Across tracers, SEOT yielded more consistently significant differences among SOCI groups than SUVR. Discussion: Both tracers showed associations with SOCI in CU individuals, with broadly comparable regional association strengths despite differences in the spatial extent and statistical significance of their findings. SEOT complemented SUVR by identifying additional significant associations and group differences. These findings suggest that tracer choice and quantification approach may influence the spatial distribution and statistical significance of observed tau-cognition relationships without necessarily altering their overall strength.
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BibTeX
@misc{macedo2026headtohead,
title = {{Head-to-Head Comparison of Flortaucipir and MK6240 tau-PET to Detect Subtle Objective Cognitive Impairment in Clinically Unimpaired Individuals}},
author = {A. C. Macedo and E. Aumont and L. Trudel and S. A. Hosseini and J. Therriault and G. Bezgin and A. Lebrun and D. Oliva-Lopez and F. Z. Lussier and T. Chan and C. Tissot and N. Rahmouni and B. Hall and I. Bizzi and C. Boccalini and J. Beker Godoy and G. Povala and P. C. L. Ferreira and B. Bellaver and J. Fernandez-Arias and L. Amaral and E. Ruppert and M. Scop Medeiros and R. Mroue and A. Rocha and M. Montembeault and B. Pascual and J. Masdeu and B. A. Gordon and V. J. Lowe and H. Oh and D. N. Soleimani-Meigooni and J. Fortea and S. Baker and T. A. Pascoal and P. Rosa-Neto},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.01.26367030},
url = {https://www.medrxiv.org/content/10.64898/2026.11.01.26367030v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Head-to-Head Comparison of Flortaucipir and MK6240 tau-PET to Detect Subtle Objective Cognitive Impairment in Clinically Unimpaired Individuals
AU - A. C. Macedo
AU - E. Aumont
AU - L. Trudel
AU - S. A. Hosseini
AU - J. Therriault
AU - G. Bezgin
AU - A. Lebrun
AU - D. Oliva-Lopez
AU - F. Z. Lussier
AU - T. Chan
AU - C. Tissot
AU - N. Rahmouni
AU - B. Hall
AU - I. Bizzi
AU - C. Boccalini
AU - J. Beker Godoy
AU - G. Povala
AU - P. C. L. Ferreira
AU - B. Bellaver
AU - J. Fernandez-Arias
AU - L. Amaral
AU - E. Ruppert
AU - M. Scop Medeiros
AU - R. Mroue
AU - A. Rocha
AU - M. Montembeault
AU - B. Pascual
AU - J. Masdeu
AU - B. A. Gordon
AU - V. J. Lowe
AU - H. Oh
AU - D. N. Soleimani-Meigooni
AU - J. Fortea
AU - S. Baker
AU - T. A. Pascoal
AU - P. Rosa-Neto
PY - 2026
DA - 2026/11/01
PB - medRxiv
DO - 10.64898/2026.11.01.26367030
UR - https://www.medrxiv.org/content/10.64898/2026.11.01.26367030v1
AB - Background and Objectives: Tau-PET is associated with subtle objective cognitive impairment (SOCI) in clinically unimpaired (CU) individuals, but whether the spatial patterns and strengths of these associations differ across tracers remains unclear. We performed a head-to-head comparison of [18F]MK6240 and [18F]flortaucipir to investigate their associations with SOCI in CU individuals. Methods: We cross-sectionally assessed CU participants from the HEAD study who underwent both tau-PET scans. Linear regressions examined associations between domain-specific cognition and tau burden using standardized uptake value ratios (SUVR) in regional and voxelwise analyses, alongside regional spatial extent of tauopathy (SEOT) measures. Tau burden was compared across groups representing different levels of SOCI. Models adjusted for age, sex, and education, with additional adjustment for amyloid-beta burden. Centiloid-stratified analyses examined associations across amyloid-beta burden levels. Results: Among 297 participants (mean [SD] age, 67.0 [8.4] years; 179 [60.3%] female), higher [18F]MK6240 SUVR was associated with poorer memory performance. Greater SEOT with either tracer was associated with poorer memory and showed nominal associations with executive dysfunction. Regional association strengths did not differ significantly between tracers, while SEOT yielded comparable or stronger associations than SUVR. Centiloid-stratified analyses revealed tau-cognition associations primarily at intermediate and high amyloid-beta burden. [18F]MK6240 showed more spatially extensive voxelwise associations with memory and across SOCI group comparisons. Regional analyses also yielded more statistically significant differences across SOCI groups with [18F]MK6240 than with flortaucipir. These differences were predominantly driven by participants meeting actuarial mild cognitive impairment criteria, who exhibited greater tau burden than groups with less pronounced psychometric impairment. Across tracers, SEOT yielded more consistently significant differences among SOCI groups than SUVR. Discussion: Both tracers showed associations with SOCI in CU individuals, with broadly comparable regional association strengths despite differences in the spatial extent and statistical significance of their findings. SEOT complemented SUVR by identifying additional significant associations and group differences. These findings suggest that tracer choice and quantification approach may influence the spatial distribution and statistical significance of observed tau-cognition relationships without necessarily altering their overall strength.
ER -