Abstract
The purpose of this study was to determine whether metrics of brain tissue integrity derived from postmortem magnetic resonance imaging (MRI) are associated with late-life cognitive decline, independent of cerebral vessel disease. Using data from 554 older adults, we used voxelwise regression to identify regions where the postmortem MRI transverse relaxation rate constant R(2) was associated with the rate of decline in global cognition. We then used linear mixed models to investigate the association between a composite R(2) measure and cognitive decline, controlling for neuropathology including 3 indices of vessel disease: atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. This composite R(2) measure was associated with the rate of decline (0.049 unit annually per R(2) unit, p < 0.0001) and accounted for 6.1% of its variance, beyond contributions from vessel disease indices and other prominent age-related neuropathologies. Thus, postmortem brain R(2) reflects disease processes underlying cognitive decline that are not captured by vessel disease indices or other standard neuropathologic indices and may provide a measure of brain tissue integrity that is complementary to histopathologic evaluation.