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Clinical Manifestations.

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Area of Science:

  • Neurology
  • Nuclear Medicine
  • Biomarkers

Background:

  • The Alzheimer's Association (AA-2024) criteria propose four biological stages for Alzheimer Disease (AD) based on PET imaging.
  • Variations in tau PET tracers can influence the application of these biological stages.
  • Understanding tracer-specific performance is crucial for accurate AD staging.

Purpose of the Study:

  • To compare the diagnostic performance of biological staging for Alzheimer Disease using two distinct tau PET tracers: MK-6240 and Flortaucipir (FTP).
  • To assess the concordance between clinical and biological stages of AD defined by AA-2024 criteria.
  • To evaluate the impact of different tau PET tracers on the classification of AD stages.

Main Methods:

  • Analysis of 446 individuals, including 167 Aβ-positive participants from the HEAD study, who underwent both MK-6240 and Flortaucipir (FTP) tau PET scans.
  • Clinical staging (normal, transitional, MCI, dementia) based on AA-2024 criteria, with specific focus on stage-2 subgroups (SCD, SOCD, MBI).
  • Biological staging using tracer-specific thresholds for regional SUVR with two regions of interest schemes (AA-2024 and Braak stages); assessed agreement using Cohen's kappa and calculated positive predictive values (PPV).

Main Results:

  • Both tracers showed progressively increased amyloid-β (Aβ) positivity and tau PET pathology across clinical stages from cognitively normal to dementia.
  • Subjective cognitive decline (SCD) and mild behavioral impairment (MBI) subgroups did not show increased pathology compared to cognitively normal individuals.
  • Subtle objective cognitive decline (SOCD) was identified as a relevant transitional stage (stage 2) with higher pathological burden; moderate agreement (0.34-0.59) was observed between clinical and biological stages for both tracers, with MK-6240 showing lower PPV in earlier stages than FTP.

Conclusions:

  • The AA-2024 biological and clinical stages demonstrate similar concordance when using either Flortaucipir or MK-6240 tau PET tracers.
  • The SOCD transitional stage exhibits a higher pathological burden compared to stage 1, unlike SCD and MBI subgroups.
  • Findings support the utility of both tracers for AD staging, while highlighting method-dependent variations in performance.