Healthy and pathological aging influence brain microstructure via complex processes. Discerning these processes requires measurements that are sensitive to specific biological properties of brain tissue. We integrated a novel quantitative R1 measure with multi-shell diffusion weighted imaging to map age-associated changes in macromolecular tissue volume (MTV) along major white matter tracts in healthy older adults and patients with amnestic Mild Cognitive Impairment (aMCI). Reduced MTV in association tracts was associated with older age in healthy aging, was correlated with memory performance, and distinguished aMCI from controls. We also mapped changes in gray matter tissue properties using quantitative R1 measurements. We documented a widespread decrease in R1 with advancing age across the cortex and decreased R1 in aMCI compared with controls in regions implicated in episodic memory. Our data are the first to characterize MTV loss along major white matter tracts in aMCI and suggest that qMRI is a sensitive measure for detecting subtle degeneration of white and gray matter tissue that cannot be detected by conventional MRI and diffusion measures.
