Abstract
Improved characterization of the microstructural brain changes occurring in the early stages of Alzheimer's disease may permit more timely disease detection. This study examined how longitudinal change in brain microstructure relates to cognitive decline in aging and prodromal Alzheimer's disease. At baseline and two-year follow-up, 29 healthy controls and 21 individuals with mild cognitive impairment or mild Alzheimer's disease underwent neuropsychological evaluation and restriction spectrum imaging (RSI). Microstructural change in the hippocampus, entorhinal cortex, and white matter tracts previously shown to be vulnerable to Alzheimer's disease, was compared between healthy controls and impaired participants. Partial correlations and stepwise linear regressions examined whether baseline RSI metrics predicted subsequent cognitive decline, or change in RSI metrics correlated with cognitive change. In medial temporal gray and white matter, restricted isotropic diffusion and crossing fibers were lower, and free water diffusion was higher, in impaired participants. Restricted isotropic diffusion in the hippocampus declined more rapidly for cognitively impaired participants. Baseline hippocampal restricted isotropic diffusion predicted cognitive decline, and change in hippocampal and entorhinal restricted isotropic diffusion correlated with cognitive decline. Within controls, changes in white matter restricted oriented diffusion and crossing fibers correlated with memory decline. In contrast, there were no correlations between rates of cortical atrophy and cognitive decline in the full sample or within controls. Changes in medial temporal lobe microarchitecture were associated with cognitive decline in prodromal Alzheimer's disease, and these changes were distinct from microstructural changes in normal cognitive aging. RSI metrics of brain microstructure may hold value for predicting cognitive decline in aging and for monitoring the course of Alzheimer's disease.