Cerebral amyloid angiopathy burden associated with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study - PubMed (original) (raw)

doi: 10.1002/ana.23830. Epub 2013 Feb 19.

Anand Viswanathan, Christopher Gidicsin, Trey Hedden, Sergi Martinez-Ramirez, Andrew Dumas, Anastasia Vashkevich, Alison M Ayres, Eitan Auriel, Ellis van Etten, Alex Becker, Jeremy Carmasin, Kristin Schwab, Jonathan Rosand, Keith A Johnson, Steven M Greenberg

Affiliations

Cerebral amyloid angiopathy burden associated with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study

M Edip Gurol et al. Ann Neurol. 2013 Apr.

Abstract

Objective: We hypothesized that vascular amyloid contributes to chronic brain ischemia, therefore amyloid burden measured by Pittsburgh compound B retention on positron emission tomography (PiB PET) would correlate with the extent of magnetic resonance imaging (MRI) white matter hyperintensities (WMH; or leukoaraiosis) in patients with high vascular amyloid deposition (cerebral amyloid angiopathy [CAA]) but not in patients with high parenchymal amyloid deposition (Alzheimer disease [AD]; mild cognitive impairment [MCI]) or in healthy elderly (HE) subjects.

Methods: Forty-two nondemented CAA patients, 50 HE subjects, and 43 AD/MCI patients had brain MRI and PiB PET. Multivariate linear regression was used to assess the independent association between PiB retention and white matter disease volume, controlling for age, gender, apolipoprotein E genotype, and vascular risk factors within each group.

Results: CAA patients were younger than HE and AD subjects (68 ± 10 vs 73.3 ± 7 and 74 ± 7.4, p < 0.01) but had higher amounts of WMH (median = 21 vs 3.2 and 10.8 ml, respectively, p < 0.05 for both comparisons). Global PiB retention and WMH showed strong correlation (rho = 0.52, p < 0.001) in the CAA group but not in HE or AD. These associations did not change in the multivariate models. Lobar microbleed count, another marker of CAA severity, also remained as an independent predictor of WMH volume.

Interpretation: Our results indicate that amyloid burden in CAA subjects (with primarily vascular amyloid) but not AD subjects (with primarily parenchymal amyloid) independently correlates with WMH volume. These findings support the idea that vascular amyloid burden directly contributes to chronic cerebral ischemia and highlights the possible utility of amyloid imaging as a marker of CAA severity.

Copyright © 2012 American Neurological Association.

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Figures

Figure 1

Figure 1. Comparison of WMH volume among the study cohorts

Comparison of WMH volume among the three diagnostic categories. Patients with CAA had higher WMH volume than HE (p<0.001) and AD/MCI (p=0.002) subjects. Patients with AD/MCI had higher WMH volume when compared to HE (p=0.01). These associations remained significant after adjustment for relevant covariates.

Figure 2

Figure 2. Scatterplot of PiB retention and WMH in cerebral amyloid angiopathy (CAA)

Scatterplot showing strong correlation between WMH and global DVR in cerebral amyloid angiopathy (CAA) (Spearman’s rho=0.52, p<0.001).

Figure 3

Figure 3. (A and B): Representative PiB PET and FLAIR MRIs showing correlation of amyloid deposition and WMH in 2 CAA patients

PiB PET (left) and FLAIR MRI (right) scans from 2 CAA patients with prior history of ICH, both had scans at 66 years of age. Both patients scored 30/30 on Mini-Mental Status Examination. Patient in panel 3A had a global DVR of 1.4 and WMH volume of 41ml. Patient in panel 3B had global DVR of 1.13 and WMH of 6.24ml.

Figure 4

Figure 4. Scatterplot of PiB retention and WMH in patients with Alzheimer Disease (AD) and mild cognitive impairment (MCI)

Scatterplot showing no correlation between WMH and global DVR in patients with Alzheimer Disease (AD) and mild cognitive impairment (MCI) (Spearman’s rho=0.11, p=0.47).

Figure 5

Figure 5. Scatterplot of PiB retention and WMH in healthy elderly

Scatterplot showing no correlation between WMH and global DVR in healthy elderly (Spearman’s rho=0.01, p=0.95).

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