Grey- and white-matter resilience to tau, cognition and sex in Alzheimer's disease.

INTRODUCTION

Brain resilience to tau has been mainly studied in relation to grey matter, while its role in white matter remains unclear in Alzheimer's disease (AD). Sex may moderate associations between brain resilience and cognition.

METHODS

We analyzed medial temporal lobe tau PET SUVR, entorhinal cortical thickness, cingulum-hippocampal mean diffusivity, and cognition in 205 amyloid-positive individuals from ADNI. Associations between grey- and white-matter resilience to tau and cognitive performance or decline were examined using linear and mixed-effects models, including sex interactions and stratified analyses.

RESULTS

Higher grey-matter resilience to tau related to better cross-sectional memory and language performance (p<0.005), whereas higher white-matter resilience related to slower decline in these domains (p<0.03). These associations were seen in men but not women. DISCUSSION: White-matter resilience may better capture early cognitive changes in AD. Sex differences suggest greater sensitivity of cognition to brain resilience in men.