Preserved white matter integrity is a marker of familial longevity

OBJECTIVE: Brain tissue integrity is highly heritable, and its decline is a common phenomenon of ageing. This study aimed to determine whether the phenotype of familial longevity is marked by a relative preservation of brain tissue microstructure. METHODS: Participants were enrolled in the Leiden Longevity Study. In total, 185 middle-aged to elderly offspring of nonagenarian siblings, who were enriched for familial factors of longevity, were contrasted with 171 environment- and age-matched controls. All subjects underwent 3T whole brain magnetic resonance diffusion tensor imaging. RESULTS: Voxel-wise analysis revealed widespread age-related decrease of white matter fractional anisotropy and increases of axial, radial, and mean diffusivity (all p < 0.003). Offspring showed higher mean white matter fractional anisotropy (mean [standard error]: offspring, 0.3232 [0.0009]; controls, 0.3212 [0.0009]; p = 0.04) compared to control subjects independent of cardiovascular risk factors. When differences in white matter diffusion parameters between offspring and control subjects were assessed voxel-wise, offspring showed higher white matter fractional anisotropy and lower white matter radial diffusivity predominantly in the callosal genu and body (both p < 0.003). With the effect of chronological age on white matter microstructure taken into account, offspring can be considered 4.5 years "biologically younger" compared to control subjects with regard to white matter integrity. INTERPRETATION: Both middle-aged to elderly offspring of nonagenarian siblings and control subjects show common age-related decline of white matter integrity, but it is less marked in the callosal genu and body in the offspring. This corresponds to a biological age benefit of 4.5 years of the offspring as compared to the control subjects.