Structural white matter properties and cognitive resilience to tau pathology.

Introduction: We assessed whether macro- and/or micro-structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset.

Methods: We examined whether global efficiency, an indicator of communication efficiency in brain networks, and diffusion measurements within the limbic network and default mode network moderate the association between amyloid-β/tau pathology and cognitive decline. We also investigated whether demographic and health/risk factors are associated with white matter properties.

Results: Higher global efficiency of the limbic network, as well as free-water corrected diffusion measures within the tracts of both networks, attenuated the impact of tau pathology on memory decline. Education, age, sex, white matter hyperintensities, and vascular risk factors were associated with white matter properties of both networks.

Discussion: White matter can influence cognitive resilience against tau pathology, and promoting education and vascular health may enhance optimal white matter properties.

Highlights: Aβ and tau were associated with longitudinal memory change over ∼7.5 years. White matter properties attenuated the impact of tau pathology on memory change. Health/risk factors were associated with white matter properties.