Network efficiency predicts resilience to cognitive decline in elderly at risk for Alzheimer’s

To determine whether white matter network efficiency (WMNE) may be a surrogate marker of the physiological basis of resilience to cognitive decline in elderly persons without dementia and age and AD-related cerebral pathology, we quantified WMNE from baseline MRI scans and investigated its association with longitudinal neuropsychological assessments independent of baseline amyloid, tau and white matter hyperintensity volume. 85 cognitively normal elderly subjects and patients with mild cognitive impairment (MCI) with baseline diffusion imaging, CSF specimens, AV45-PET and longitudinal cognitive assessments were included. WMNE was calculated from reconstructed cerebral white matter networks for each individual. Mixed linear effects models were estimated to investigate the association of higher resilience to cognitive decline with higher WMNE and the modulation of this association by increased cerebral amyloid, CSF tau or WMHV. For the majority of cognitive outcome measures, higher WMNE was associated with higher resilience to cognitive decline independently of pathology measures (beta: .074 – .098; p: .011 – .039). Additionally, WMNE was consistently associated with higher resilience to cognitive decline in subjects with higher cerebral amyloid burden (beta: .024 – .276; p: .000 – .036) and with lower CSF tau (beta: −.030 – −.074; p: .015 – .002) across all cognitive outcome measures. The results of this study indicate that WMNE in particular and possibly white matter organization in general may be worthy targets of investigation to provide measures quantifying a patient’s resilience to cognitive decline and thus provide an individual prognosis.