Amyloid, but not tau, is associated with longitudinal change in white matter hyperintensities in a sample of cognitively normal older adults from the Baltimore Longitudinal Study of Aging

Abstract

AbstractBackgroundWhite matter hyperintensities (WMH) are associated with a greater risk of developing dementia. Hallmark neuropathologies of Alzheimer’s disease (AD), namely, amyloid plaques and tau tangles, begin to aggregate in the brain prior to signs of cognitive impairment. To better understand the relationship between WMH and AD neuropathology in preclinical AD, we assessed via positron emission tomography (PET) and magnetic resonance imaging (MRI) if amyloid and tau are associated with the rate of change in WMH burden among cognitively normal older adults.Method89 cognitively normal participants (mean age at PET=76.7 years, 35 men) of the Baltimore Longitudinal Study on Aging underwent 3T fluid attenuated inversion recovery (FLAIR) MRI to assess global WMH burden, 11C‐Pittsburgh compound B PET to assess global amyloid status, and 18F‐flortaucipir PET to assess entorhinal cortex tau. 85 participants had additional FLAIR scan(s) prior to PET visit (mean follow‐up between first and last FLAIR=6.4 years, standard deviation=2.2 years). We assessed the associations of amyloid and tau with retrospective longitudinal WMH burden (in cm3) at and prior to PET scan via a linear mixed effects model (350 observations total). Global amyloid status, entorhinal cortex tau, and their interactions with time from PET were our explanatory variables; our model was adjusted for age at PET, sex, total white matter volume, APOE‐e4 allele carrier status, and vascular risk.ResultHigher cross‐sectional endpoint global WMH burden was associated with amyloid positivity (estimate=3.050, standard error [SE]=1.366, p=0.028), but not with entorhinal tau SUVR (estimate=−3.233, SE=4.301, p=0.456). Amyloid positivity was also associated with steeper increases in WMH burden in years preceding PET (estimate=0.277, SE=1.366, p=0.037), whereas entorhinal tau was not (estimate=−0.378, SE=0.408, p=0.354).ConclusionAmyloid, but not tau, is associated with greater global WMH volume and greater rates of global WMH volume change in our sample of cognitively normal older adults.