| Summary: | Abstract Introduction Cerebrovascular disease (CVD) is not currently considered a core pathological feature of Alzheimer's disease (AD), but mounting evidence suggests that concurrent CVD may exacerbate AD progression. The purpose of this study was first to examine the relationship among amyloid, CVD, and neurodegeneration and second to examine the extent to which amyloid and CVD pathology drive subsequent neurodegeneration over time. Methods Six hundred eight (224 normal controls, 291 mild cognitive impairment, 93 AD) subjects from the Alzheimer's Disease Neuroimaging Initiative with longitudinal AV45 positron emission tomography imaging and MR imaging were investigated. Results Amyloid and white matter hyperintensity (WMH) burden increased across clinical diagnosis groups (normal control < mild cognitive impairment < AD). Amyloid pathology and WMH volume were related to lower cortical thickness, while WMH burden was associated with neurodegenerative/atrophic changes over time in key AD‐related brain regions. Discussion CVD and AD may be etiologically independent, but our findings suggest that CVD should be considered explicitly for its effect on AD progression.
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