Increased white matter hyperintensities on MRI in autosomal dominant familial compared to sporadic Alzheimer’s disease

Background

White matter hyperintensities (WMH) on MRI may be observed in autosomal dominant familial Alzheimer’s disease (FAD) and sporadic AD (SAD), however, studies comparing WMH burden between these two groups are lacking.

Methods

In this cross-sectional study, we evaluated global and local differences in WMH severity on MRI in 19 individuals with symptomatic FAD due to Presenilin 1 mutations, 20 individuals with young-onset SAD and 19 healthy individuals, controlling for age, cerebrovascular risk factors (CVR) and APOEε4 carrier status. Relationships between WMH, grey matter (GM) volumes and neuropsychological tests (NPT) were also investigated.

Results

Despite their young age and minimal CVR, the FAD group had higher WMH load in all areas considered, apart from juxta-cortical and periventricular layers when compared to the SAD group. The increased lobar WMH load observed in FAD was not influenced by APOEε4 genotype or CVR. No significant associations were found between WMH and GM volumes or NPT in either AD group.

Conclusions

Our findings suggest that WMH may reflect aspects of AD pathology that are particularly prominent in FAD. Notably, in our study, WMH were not simply attributable to CVR, APOEε4 carrier status, or GM atrophy, but may instead represent independent features of the disease.