DEEP OCCIPITAL WHITE MATTER HYPERINTENSITIES ARE ROBUSTLY RELATED TO AMYLOID PATHOLOGY AND MAY BE AN EARLY MARKER FOR ALZHEIMER’S DISEASE

In asymptomatic carriers of autosomal dominant mutations for Alzheimer's disease (AD), occipital WMH increased about 20 years before estimated time of onset [Lee 2016]. In sporadic AD dementia, parietal WMH is relevant for the prediction of time to onset [Brickman 2012]. The aim of this study was to examine whether WMH load and location is associated with amyloid pathology, age and vascular risk factors in subjective cognitive decline (SCD) and mild cognitive impairment (MCI). 301 controls and cases with SCD or MCI were included from the longitudinal Norwegian Dementia Disease Initiation (DDI) multi-site study. We stratified on Ab1-42 pathology (Ab+/-), using an amyloid-PET verified cerebrospinal fluid (CSF) cutoff. Global, and frontal, parietal and occipital WMH volumes in deep (DWMH) and periventricular (PWMH) layers were determined using an automated algorithm [Sudre 2015], and further normalized to global or regional brain volumes, respectively. Global and regional WMH loads were log-transformed due to right-skewed distributions, and then z-transformed. WMH loads were compared between groups using analysis of covariance (ANCOVA), correcting for age and scanners. Linear regression was performed to examine associations between global or regional WMH loads, age and vascular risk factors, assessed with the simple Framingham Risk Score (FRS-CVD). Global (p=0.012), parietal DWMH (p=0.015), parietal PWMH (p=0.019), occipital DWMH (p=0.004) and occipital PWMH (p=0.001) loads were increased in SCD-Ab+ compared to asymptomatic cognitively normal Ab- controls (NC-Ab-). Only occipital DWMH load was significantly higher in MCI-Ab+ compared to MCI-Ab- (p=0.004). Only frontal PWMH and DWMH loads were positively associated with FRS-CVD without the age component (FRS-CVDwoa), after controlling for age.