Beta amyloid (A beta) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Ab burden: A beta- [mean mSUVr <= 1.00], A beta i [1.00 < mSUVr <1.17], A beta+ [mSUVr >= 1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. A beta i group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both A beta- and A beta+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled A beta-/A beta i and pooled A beta i/A beta+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising A beta burden. In the later stages of A beta accumulation, neurodegeneration is the predominant factor affecting diffusion. (C) 2020 Elsevier Inc. All rights reserved.