Evidence against a temporal association between cerebrovascular disease and Alzheimer's disease imaging biomarkers

Whether a relationship exists between cerebrovascular disease and Alzheimer's disease has been a source of controversy. Evaluation of the temporal progression of imaging biomarkers of these disease processes may inform mechanistic associations. We investigate the relationship of disease trajectories of cerebrovascular disease (white matter hyperintensity, WMH, and fractional anisotropy, FA) and Alzheimer's disease (amyloid and tau PET) biomarkers in 2406 Mayo Clinic Study of Aging and Mayo Alzheimer's Disease Research Center participants using accelerated failure time models. The model assumes a common pattern of progression for each biomarker that is shifted earlier or later in time for each individual and represented by a per participant age adjustment. An individual's amyloid and tau PET adjustments show very weak temporal association with WMH and FA adjustments (R = -0.07 to 0.07); early/late amyloid or tau timing explains <1% of the variation in WMH and FA adjustment. Earlier onset of amyloid is associated with earlier onset of tau (R = 0.57, R² = 32%). These findings support a strong mechanistic relationship between amyloid and tau aggregation, but not between WMH or FA and amyloid or tau PET.