Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus Erythematosus

Wiseman, Stewart; Bastin, Mark E.; Jardine, Charlotte; Barclay, G. Robin; Hamilton, I.; Sandeman, Elaine M.; Hunt, David; Amft, E N; Thomson, Susan; Belch, J. J. F.; Ralston, Stuart H.; Wardlaw, Joanna M.

doi:10.1161/strokeaha.116.014330

Cited by 61 publications

(58 citation statements)

References 42 publications

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“…The approach was first introduced by Staals et al . to prove the association between cSVD and lacunar stroke subtype in ischaemic stroke patients and then was widely used in studies focusing on the relationship between cSVD and systemic lupus erythematosus, aortic atheroma and mild parkinsonian signs . As far as is known, the findings here are the first not only to describe the total burden of cSVD in primary ICH but also to assess the impact of overall cSVD damage on R‐DWILs.…”

Section: Discussionmentioning

confidence: 93%

Association between remote diffusion‐weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage

et al. 2019

Euro J of Neurology

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Background and purpose The aim of this study was to examine the association amongst remote diffusion‐weighted imaging lesions (R‐DWILs), imaging markers of cerebral small vessel disease (cSVD) and total cSVD burden in patients with primary intracerebral haemorrhage (ICH). Methods In total, 344 consecutive primary ICH patients were enrolled prospectively. R‐DWILs on magnetic resonance imaging as well as four imaging markers of cSVD, including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), lacunes and enlarged perivascular spaces, were rated with validated scales. The total cSVD score was calculated by adding up these four markers. Univariate and multivariate analyses were performed. Results Remote DWI lesions were detected in 57 (16.6%) primary ICH patients. On multivariate logistic regression analysis, the presence of CMBs [odds ratio (OR) 5.26, 95% confidence interval (CI) 1.72–16.12], of high‐grade WMHs (OR 4.68, 95% CI 2.01–10.90), the presence of lacunes (OR 2.69, 95% CI 1.20–6.06), mixed CMBs (OR 2.93, 95% CI 1.35–6.36), mixed lacunes (OR 3.60, 95% CI 1.25–10.37), periventricular WMHs (OR 2.19, 95% CI 1.40–3.44), deep WMHs (OR 1.92, 95% CI 1.24–2.97) and total WMHs (OR 1.52, 95% CI 1.20–1.94) were associated with the presence of R‐DWILs. A significant association was also found between high‐grade total cSVD score and R‐DWILs (OR 1.97, 95% CI 1.36–2.84). This association remained significant in patients stratified by an age of 60 years or more than 60 years. Conclusions Remote DWI lesions are correlated with the severity of each imaging marker of cSVD and with the total burden of cSVD.

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Section: Discussionmentioning

confidence: 93%

Association between remote diffusion‐weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage

et al. 2019

Euro J of Neurology

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“…It remains unclear whether the Ab in accumulated plaque in the cortical blood vessels is derived from the circulation, the blood vessel wall itself, or from the central nervous system 30 A disadvantage associated with using EC-APP770 + mice is the increased expression of Aiolos due to insertion of the floxed APP transgene within the intron of the gene encoding for Aiolos, Ikzf3. Aiolos overexpression has been reported in B cells from patients with systemic lupus erythematosus (SLE) 36 , while it was recently shown that the cerebral small blood vessel disease burden is increased in SLE 37 . By crossing with AD model mice, both EC-APP770 + and EC-APP770mice exhibited amyloid plaques in the cerebral small blood vessels, an effect that is likely related to the SLE-like features.…”

Section: Discussionmentioning

confidence: 99%

Endothelial expression of human APP leads to cerebral amyloid angiopathy in mice

Tachida

Miura

Imamaki

et al. 2020

Preprint

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The deposition of amyloid β (Aβ) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in more than 90% of Alzheimer’s disease (AD) patients. The presence of such CAA pathology is not as evident, however, in most mouse models of AD, thereby making it difficult to examine the contribution of CAA to the pathogenesis of AD. Since blood levels of soluble amyloid precursor protein (sAPP) in rodents are less than 1% of those in humans, we hypothesized that endothelial APP expression would be markedly lower in rodents, thus providing a reason for the poorly expressed CAA pathology. Here we generated mice that specifically express human APP770 in endothelial cells. These mice exhibited an age-dependent robust deposition of Aβ in brain blood vessels but not in the parenchyma. Crossing these animals with APP knock-in mice led to an expanded CAA pathology as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results show that both neuronal and endothelial APP contribute cooperatively to vascular Aβ deposition, and suggest that this mouse model will be useful for studying disease mechanisms underlying CAA and for developing novel AD therapeutics.

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“…Brain MRI acquisition parameters were broadly the same across all participant groups and have been described in detail previously. 11,14,16,17 The brain health index…”

Section: Brain Mri Acquisitionmentioning

confidence: 99%

The brain health index: Towards a combined measure of neurovascular and neurodegenerative structural brain injury

Dickie

Hernández

Makin

et al. 2018

International Journal of Stroke

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Background A structural magnetic resonance imaging measure of combined neurovascular and neurodegenerative burden may be useful as these features often coexist in older people, stroke and dementia. Aim We aimed to develop a new automated approach for quantifying visible brain injury from small vessel disease and brain atrophy in a single measure, the brain health index. Materials and methods We computed brain health index in N = 288 participants using voxel-based Gaussian mixture model cluster analysis of T1, T2, T2*, and FLAIR magnetic resonance imaging. We tested brain health index against a validated total small vessel disease visual score and white matter hyperintensity volumes in two patient groups (minor stroke, N = 157; lupus, N = 51) and against measures of brain atrophy in healthy participants (N = 80) using multiple regression. We evaluated associations with Addenbrooke's Cognitive Exam Revised in patients and with reaction time in healthy participants. Results The brain health index (standard beta = 0.20-0.59, P < 0.05) was significantly and more strongly associated with Addenbrooke's Cognitive Exam Revised, including at one year follow-up, than white matter hyperintensity volume (standard beta = 0.04-0.08, P > 0.05) and small vessel disease score (standard beta = 0.02-0.27, P > 0.05) alone in both patient groups. Further, the brain health index (standard beta = 0.57-0.59, P < 0.05) was more strongly associated with reaction time than measures of brain atrophy alone (standard beta = 0.04-0.13, P > 0.05) in healthy participants. Conclusions The brain health index is a new image analysis approach that may usefully capture combined visible brain damage in large-scale studies of ageing, neurovascular and neurodegenerative disease.

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Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus Erythematosus

Abstract: Supplemental Digital Content is available in the text.

Cited by 61 publications

References 42 publications

Association between remote diffusion‐weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage

Association between remote diffusion‐weighted imaging lesions and cerebral small vessel disease in primary intracerebral hemorrhage

Endothelial expression of human APP leads to cerebral amyloid angiopathy in mice

The brain health index: Towards a combined measure of neurovascular and neurodegenerative structural brain injury

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