# Associations between brain and cognitive resilience, tau load and extent in Alzheimer's disease

## TL;DR

This study explores how brain and cognitive resilience relate to tau pathology in Alzheimer's disease, finding that a measure called SEOT may better predict cognitive decline than traditional methods.

## Contribution

The study introduces SEOT as a potentially more sensitive biomarker for cognitive decline in Alzheimer's disease compared to SUVR.

## Key findings

- Whole Cortex SEOT shows a stronger negative correlation with MMSE scores than SUVR, suggesting it is a more sensitive marker of cognitive decline.
- MCI patients maintain higher MMSE scores despite tau accumulation, while AD patients show greater variability and decline.
- SEOT may serve as a more effective biomarker for tracking disease progression in Alzheimer's and MCI.

## Abstract

Brain and cognitive resilience (BR, CR) reflect the capacity to maintain structural integrity and cognitive function despite pathological tau deposition in Alzheimer's disease (AD). Tau pathology can be characterized in terms of spatial extent of tauopathy (SEOT) or load using standardized uptake value ratio (SUVR). The aim was to compare SEOT and SUVR in their association with BR and CR. To replicate findings from Ossenkoppele et al. (2020) using MK‐6240 PET imaging and evaluate demographic, genetic, and imaging factors associated with BR and CR. The objective of this study is to assess the value of SEOT metrics in resilience models and compare their predictive power to standardized uptake value ratio (SUVR) and to evaluate cross sectional interactions between tau pathology, cognitive resilience, and cognitive decline.

We assessed 126 amyloid‐β‐positive participants TRIAD cohort with tau‐PET using [18F]MK6240 and cognitive assessments (MMSE). SEOT was quantified as the proportion of voxels considered as abnormal relative to young controls. We used Participants recruited from TRIAD cohort, including individuals with mild cognitive impairment (MCI) or AD, positive amyloid‐β biomarkers, MK‐6240 PET imaging data.

Higher Whole Cortex MK SUVR is associated with lower MMSE scores, showing increased tau pathology correlates with cognitive decline. MCI patients maintain higher MMSE scores despite some tau accumulation, while AD patients show greater variability and decline. The negative trend suggests tau deposition contributes to cognitive impairment, but other factors may also play a role.

2. Whole Cortex MK SUVR vs. MMSE the negative correlation between Whole Cortex SEOT and MMSE appears stronger, with a more pronounced decline in cognitive function (MMSE scores) as SEOT increases, suggesting SEOT may be a more sensitive marker of disease progression in AD patients.

Whole Cortex SEOT exhibits a stronger negative correlation with MMSE compared to Whole Cortex MK‐6240 SUVR, indicating that SEOT may serve as a more sensitive marker of cognitive decline in Alzheimer's disease and mild cognitive impairment. Further research is needed to validate SEOT's potential as a diagnostic or prognostic biomarker in neurodegenerative conditions.