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: Functional imaging studies have demonstrated the recruitment of additional neural resources as a possible mechanism to compensate for age and Alzheimer’s disease (AD)-related cerebral pathology, the efficacy of which is potentially modulated by underlying structural network connectivity. Additionally, structural network efficiency (SNE) is associated with intelligence across the lifespan, which is a known factor for resilience to cognitive decline. We hypothesized that SNE may be a surrogate of the physiological basis of resilience to cognitive decline in elderly persons without dementia and with age- and AD-related cerebral pathology. Methods : We included 85 cognitively normal elderly subjects or mild cognitive impairment (MCI) patients submitted to baseline diffusion imaging, liquor specimens, amyloid-PET and longitudinal cognitive assessments. SNE was calculated from baseline MRI scans using fiber tractography and graph theory. Mixed linear effects models were estimated to investigate the association of higher resilience to cognitive decline with higher SNE and the modulation of this association by increased cerebral amyloid, liquor tau or WMHV.  Results : For the majority of cognitive outcome measures, higher SNE was associated with higher resilience to cognitive decline ( p -values: 0.011–0.039). Additionally, subjects with higher SNE showed more resilience to cognitive decline at higher cerebral amyloid burden ( p -values: <0.001–0.036) and lower tau levels ( p -values: 0.002–0.015). Conclusion : These results suggest that SNE to some extent may quantify the physiological basis of resilience to cognitive decline most effective at the earliest stages of AD, namely at increased amyloid burden and before increased tauopathy.

Structural Network Efficiency Predicts Resilience to Cognitive Decline in Elderly at Risk for Alzheimer’s Disease