Dataset Information

Posterior white matter disease distribution as a predictor of amyloid angiopathy.

ABSTRACT:

Objectives

We sought to examine whether a posterior distribution of white matter hyperintensities (WMH) is an independent predictor of pathologically confirmed cerebral amyloid angiopathy (CAA) and whether it is associated with MRI markers of CAA, in patients without lobar intracerebral hemorrhage.

Methods

We developed a quantitative method to measure anteroposterior (AP) distribution of WMH. A retrospective cohort of patients without intracerebral hemorrhage and with pathologic evaluation of CAA was examined to determine whether posterior WMH distribution was an independent predictor of CAA (n=59). The relationship of AP distributions of WMH to strictly lobar microbleeds (MBs) (n=259) and location of dilated perivascular spaces (DPVS) (n=85) was examined in a separate cohort of patients evaluated in a memory clinic.

Results

A more posterior WMH distribution was found to be an independent predictor of pathologic evidence of CAA (p=0.001, odds ratio [95% confidence interval]=1.19 [1.07-1.32]), even in the subgroup without lobar MBs (p=0.016, odds ratio [95% confidence interval]=1.18 [1.03-1.36]). In the memory clinic cohort, strictly lobar MBs were independently associated with more posterior WMH distribution (p=0.009). AP distribution of WMH was also associated with location of DPVS (p=0.001), in that patients with predominant DPVS in the white matter over the basal ganglia harbored a more posterior WMH distribution.

Conclusions

Our results suggest that AP distribution of WMH may represent an additional marker of CAA, irrespective of the presence of lobar hemorrhages.

Classification of evidence

This study provides Class III evidence that there is a significant association between the AP distribution of WMH on MRI with the presence of pathologically confirmed CAA pathology.

SUBMITTER: Thanprasertsuk S

PROVIDER: S-EPMC4155043 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Publications

Posterior white matter disease distribution as a predictor of amyloid angiopathy.

Thanprasertsuk Sekh S Martinez-Ramirez Sergi S Pontes-Neto Octavio Marques OM Ni Jun J Ayres Alison A Reed Anne A Swords Kyleen K Gurol M Edip ME Greenberg Steven M SM Viswanathan Anand A

Neurology 20140725 9

<h4>Objectives</h4>We sought to examine whether a posterior distribution of white matter hyperintensities (WMH) is an independent predictor of pathologically confirmed cerebral amyloid angiopathy (CAA) and whether it is associated with MRI markers of CAA, in patients without lobar intracerebral hemorrhage.<h4>Methods</h4>We developed a quantitative method to measure anteroposterior (AP) distribution of WMH. A retrospective cohort of patients without intracerebral hemorrhage and with pathologic e ...[more]

PMID: 25063759

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Project description:IntroductionWhite matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer's disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD.Participants and methodsParticipants (n = 175, mean age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds.ResultsMutation carriers were more likely to have microbleeds than non-carriers (p<0.05) and individuals with microbleeds had higher WMH volume than those without (p<0.05). Total WMH volume was increased in mutation carriers compared with non-carriers, up to 20 years prior to EYO, after controlling for microbleed status, as we demonstrated previously. Formal testing of mediation demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds (p = 0.03) but a significant direct effect of WMH remained (p = 0.02) after controlling for presence of microbleeds.DiscussionAlthough there is some co-dependency between WMH and microbleeds, the observed increases in WMH among mutation carriers does not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.

Dataset Information

Posterior white matter disease distribution as a predictor of amyloid angiopathy.

Objectives

Methods

Results

Conclusions

Classification of evidence

Publications

Posterior white matter disease distribution as a predictor of amyloid angiopathy.

Similar Datasets

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