The temporal relationships between white matter hyperintensities, neurodegeneration, amyloid beta, and cognition

INTRODUCTION: Cognitive decline in Alzheimer's disease is associated with amyloid beta (Aβ) accumulation, neurodegeneration, and cerebral small vessel disease, but the temporal relationships among these factors is not well established. METHODS: Data included white matter hyperintensity (WMH) load, gray matter (GM) atrophy and Alzheimer's Disease Assessment Scale‐Cognitive‐Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (Aβ1–42) for 461 participants from the Alzheimer's Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships among baseline WMH, GM, and Aβ1–42 to changes in WMH, GM, Aβ1–42, and cognition at 1‐year follow‐up. RESULTS: Baseline WMHs and Aβ1–42 predicted WMH increase and GM atrophy. Baseline WMHs and Aβ1–42 predicted worsening cognition. Only baseline Aβ1–42 predicted change in Aβ1–42. DISCUSSION: Baseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline Aβ1–42 predicted WMH increase, suggesting a potential role of amyloid in WM damage.