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In this chapter, we describe the use of quantitative metrics of white matter obtained from the diffusion tensor model based on diffusion-weighted imaging in Alzheimer’s disease (AD). Our description synthesizes insights not only from patient populations with AD dementia but also from participants at risk for AD dementia (e.g., amnestic mild cognitive impairment, subjective cognitive decline, or familial AD mutation carriers). A reference to studies examining correlations with behavioral variables is also included. Our main message is to caution against the overinterpretation of diffusion metrics and to favor analyses that focus on regions of interest or major white matter tracts for biomarker studies in AD.