The spatial-temporal relationships between gray and white matter (WM) degeneration during preclinical and early symptomatic Alzheimer's disease are poorly understood. We characterized β-amyloid deposition, cortical volume and WM degeneration in 44 subjects including healthy control (N=23), amnestic mild cognitive impairment (aMCI) (N=19), and early Alzheimer's subjects (N=2). Integrated PET-MRI provided simultaneous measurement of 18F-Florbetapir uptake in cortical areas, regional brain volumes from structural MRI, and WM tract integrity metrics from diffusion MRI using biophysical modeling. Across the cohort of healthy control and aMCIs, cortical volumes correlated poorly with β-amyloid deposition in the same area (p < 0.05 only in the posterior cingulate and parietal lobe). WM degeneration correlated significantly with both amyloid and volume of connected cortical areas, but more strongly with volume. Diffusion MRI metrics for WM demyelination and/or axonal loss could therefore provide new biomarkers associated with clinical Alzheimer's conversion. These WM changes may represent sequential propagation of Alzheimer's neurodegeneration between functionally connected regions, and/or evidence of direct WM injury during the Alzheimer's pathology cascade.

Spatial relationships between white matter degeneration, amyloid load and cortical volume in amnestic mild cognitive impairment