Data from: White matter hyperintensities and CSF AD biomarkers in preclinical Alzheimer’s disease

Objective: Recent studies suggest that white matter hyperintensities (WMH)
on MRI, which primarily reflect small vessel cerebrovascular disease, may
play a role in the evolution of Alzheimer’s disease (AD). In a
longitudinal study, we investigated whether WMH promote the progression of
AD pathology, or alter the association between AD pathology and risk of
progression from normal cognition to mild cognitive impairment (MCI).
Methods: Two sets of analyses were conducted. The relationship between
whole brain WMH load, based on FLAIR MRI images, obtained in initially
cognitively normal participants (n=274) and time to onset of symptoms of
MCI (n=60) was examined using Cox regression models. In a subset of the
participants with both MRI and CSF data (n=204), the interaction of WMH
load and CSF AD biomarkers was also evaluated. Results: Baseline WMH load
interacted with CSF t-tau with respect to symptom onset, but not with CSF
abeta1-42 or p-tau181. WMH volume was associated with time to symptom
onset of MCI among individuals with low t-tau [HR=1.35, CI=1.06-1.73,
p=0.013], but not those with high t-tau [HR=0.86,CI=0.56-1.32, p=0.47].
The rate of change in the CSF biomarkers over time was not associated with
the rate of change in WMH volumes. Conclusions and Relevance: These
results suggest that WMH primarily affect the risk of progression when CSF
measures of neurodegeneration or neuronal injury (as reflected by t-tau)
are low. However, CSF biomarkers of amyloid and p-tau and WMH appear to
have largely independent and non-synergistic effects on the risk of
progression to MCI.