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

Abstract

The spatial-temporal relationships between gray and white matter (WM) degeneration during preclinical and early symptomatic Alzheimers disease are poorly understood. We characterized {beta}-amyloid deposition, cortical volume and WM degeneration in 44 subjects including healthy control (N=23), amnestic mild cognitive impairment (aMCI) (N=19), and early Alzheimers 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.\n\nAcross the cohort of healthy control and aMCIs, cortical volumes correlated poorly with {beta}-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 Alzheimers conversion. These WM changes may represent sequential propagation of Alzheimers neurodegeneration between functionally connected regions, and/or evidence of direct WM injury during the Alzheimers pathology cascade.