Head-to-Head Comparison of Flortaucipir and MK6240 tau-PET to Detect Subtle Objective Cognitive Impairment in Clinically Unimpaired Individuals

In 297 clinically unimpaired HEAD study participants, higher 18FMK6240 tau-PET SUVR and greater SEOT were linked to poorer memory, with MK6240 showing more extensive voxelwise effects.

• Why it matters: Tau-PET is linked to subtle objective cognitive impairment, but it is unclear whether different tracers produce distinct spatial patterns and association strengths that could affect interpretation.
• What they did: Cross-sectional linear regressions related domain cognition to regional and voxelwise tau burden using 18FMK6240 versus 18Fflortaucipir SUVR and SEOT, adjusting for age, sex, education, and amyloid-beta burden. Centiloid-stratified analyses tested associations across amyloid-beta levels.
• The result: Regional association strengths were not significantly different between tracers, while SEOT showed comparable or stronger and more consistently significant SOCI group differences than SUVR, especially at intermediate/high amyloid-beta burden. MK6240 produced more spatially extensive voxelwise memory associations and more statistically significant SOCI group differences, largely driven by those meeting actuarial mild cognitive impairment criteria.

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