Increased white matter hyperintensity burden on MRI in autosomal dominant familial compared to young onset sporadic Alzheimer’s disease.

Abstract

AbstractBackgroundWhite matter hyperintensities (WMH) on MRI may be observed in familial and sporadic AD. However, studies comparing WMH burden between these two groups are lacking. We conducted this study to evaluate the load and distribution of WMH in individuals with autosomal dominant familial Alzheimer’s disease (FAD) and young onset sporadic AD (SAD), their relationship to grey matter volumes and to neuropsychological test scores (NPT).MethodIn 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 control subjects, controlling for age, cerebrovascular risk (CVR) and APOEε4 carrier status. Relationships between WMH, grey matter (GM) volumes and NPT were also investigated.ResultThe FAD group had higher WMH load in all the areas considered apart from juxta‐cortical and periventricular layers when compared to the SAD group. The two groups were well matched for disease duration and severity of cognitive impairment as assessed by the MMSE. APOEε4 genotype and cardiovascular risk factors acted as negative confounders in the identified differences in WMH volumes. There was no association between WMH and GM volumes or NPT in either AD group.ConclusionDespite their young age and minimal CVR, the FAD group in this study had a higher load of WMH compared to the SAD group, suggesting that WMH may reflect aspects of AD pathology that are particularly prominent in FAD. Our analysis suggests that APOEε4 genotype and cardiovascular risk factors may have a greater influence on WMH burden in SAD than in FAD. Furthermore, we did not identify a correlation between WMH load and GM volumes in either group, suggesting that WMH are not merely correlates of GM pathology in AD but may represent independent features of the disease.