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.