Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns

Abstract

White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH ( p = 0.001) and occipital DWMH ( p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH ( p = 0.003), as well as occipital DWMH ( p = 0.001) and temporal DWMH ( p = 0.002) loads. FRS-CVD was associated with frontal PWMHs ( p = 0.003) and frontal DWMHs ( p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.

White matter hyperintensity topography in Alzheimer's disease and links to cognition

“…A few studies showed a posterior predominance of WMH in AD. 7,9,10 Moreover, WMH in posterior regions were found to predict incident AD 32,60,61 and to increase several years before the expected symptom onset in autosomal-dominant AD. 62 In line with these previous reports, we showed that parietal, temporal, and occipital WMH were more strongly associated with AD than frontal WMH.…”

“…The regional specificity of WMH has rarely been investigated. A few studies showed a posterior predominance of WMH in AD 7,9,10 . Moreover, WMH in posterior regions were found to predict incident AD 32,60,61 and to increase several years before the expected symptom onset in autosomal‐dominant AD 62 .…”

“…This is particularly relevant as the spatial distribution of WMH seems to be associated with partially distinct etiologies. In fact, while anterior WMH have been associated with physiological aging and VRF, posterior WMH would be more specifically associated with AD 10,32,33 . Moreover, periventricular WMH seem to be more strongly associated with worse cognition than deep WMH 4,27,34,35 .…”

“…In fact, while anterior WMH have been associated with physiological aging and VRF, posterior WMH would be more specifically associated with AD. 10,32,33 Moreover, periventricular WMH seem to be more strongly associated with worse cognition than deep WMH. 4,27,34,35 Finally, studies also showed stronger links with cognition for WMH in strategic white matter tracts, such as the forceps minor or anterior thalamic radiation, than for total WMH burden.…”

White Matter and Alzheimer’s Disease: A Bidirectional Mendelian Randomization Study

“…Moreover, AD pathology was more likely to have a detrimental impact on WM lesions. Previous studies detected that Aβ pathology developed early cerebral blood flow reductions [ 13 ] and brain amyloid could increase the posterior WMH loads [ 14 ]. Amyloid accumulation also had a worse effect on white matter integrity in the absence of cognitive impairment, particularly in amyloid stage I–II [ 15 ].…”