ADAS-Cog11 performance as a surrogate of tau PET burden in an Asian Alzheimer's disease cohort

Abstract

Background

Tau pathology is the primary biological predictor of cognitive decline in Alzheimer's disease (AD). However, the high cost and limited availability of tau positron emission tomography (PET), particularly in Asian clinical settings, necessitate practical surrogate indicators of tau burden.

Objective

To determine if cognitive performance—specifically the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11)—can serve as an accessible surrogate for global tau PET burden in amyloid-positive individuals.

Methods

In this cross-sectional study of 182 participants (65 amyloid-positive) underwent ¹⁸F-florbetapir amyloid PET, ¹⁸F-florzolotau tau PET, magnetic resonance imaging (MRI), and standardized neuropsychological testing. Global tau standardized uptake value ratios (SUVr) were categorized into low, intermediate, and high using a data-driven AD-vulnerable meta-volume of interest. Associations among cognition, amyloid Centiloid (CL) values, and tau burden were examined. ROC analyses identified cognitive thresholds discriminating elevated tau burden.

Results

Tau SUVr increased progressively with diagnostic severity, whereas amyloid CL values did not associate with cognitive scores within amyloid-positive or amyloid-negative subgroups. In contrast, ADAS-Cog11 (R² = 0.46) and Free and Cued Selective Reminding Test delayed recall (R² = 0.20) were significantly associated with global tau SUVr (all p < 0.05). ADAS-Cog11 > 25 discriminated elevated tau burden with good diagnostic performance (AUC = 0.85; sensitivity 61.5%; specificity 90%). Amyloid CL values did not significantly distinguish high tau burden (p = 0.24).

Conclusions

ADAS-Cog11 provides an accessible complementary indicator of global tau burden independent of amyloid deposition. An ADAS-Cog11 cutoff >25 may aid clinical stratification for anti-amyloid therapies in settings where tau PET is unavailable, supporting scalable and accessible precision assessment in AD care.