Association of Cerebral Small Vessel Disease and Cognitive Decline After Intracerebral Hemorrhage

Pasi, Marco; Sugita, Lansing; Xiong, Li; Charidimou, Andreas; Boulouis, Grégoire; Pongpitakmetha, Thanakit; Singh, Smita; Kourkoulis, Christina; Schwab, Kristin; Greenberg, Steven M.; Anderson, Christopher; Gurol, M. Edip; Rosand, Jonathan; Viswanathan, Anand; Biffi, Alessandro

doi:10.1212/wnl.0000000000011050

Cited by 69 publications

(90 citation statements)

References 30 publications

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“…Developmental defects in the middle layer of the arterial wall, arteriosclerosis and hypertension are three important factors for cerebral hemorrhage, among which hypertension is an important independent risk factor for cerebral hemorrhage [19]. Although the pathogenesis of HICH is not yet complete, it is currently believed that hypertension is an important basis for its pathogenesis, that is, hypertension induces mechanical stress changes to act on endothelial cells (ECs), causing a series of pathological changes, resulting in vascular wall damage [20]. However, the molecular mechanism of HICH is less studied.…”

Section: Discussionmentioning

confidence: 99%

miR-20a-5p/RBM24 Axis Alleviated Hypertensive Intracerebral Hemorrhage via Regulating HIF1α/VEGFA Signaling Pathway

Xu¹,

Mo²,

Lü³

et al. 2021

Preprint

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Background: Hypertensive intracerebral hemorrhage presented high incidence and high mortality owing to its difficult to diagnose. However, the molecular mechanism of HICH remains unclear. Therefore, this study aims to investigate the key miRNAs and the mechanism of the key miRNAs in HICH. Methods: miRNAs chip was used to explore the differentially expressed miRNAs in HICH patients. In vitro and in vivo HICH models were established by Ang-II. Cell Counting Kit-8 (CCK8), flow cytometry, transwell assay and tube formation analysis were used to detect cell proliferation, apoptosis, cell migration and tube formation, respectively. Hematoxylin-eosin staining was used to evaluate the intracerebral hemorrhage in vivo HICH model. The regulatory mechanism of miR-20a-5p in HICH was confirmed by dual luciferase reporter assay, immunofluorescence, qRT-PCR, western blot and rescue experiments. Results: miR-20a-5p showed the most downregulated in HICH patients compared with healthy individuals and significantly associated with clinicopathological characteristics of HICH. Upregulation of miR-20a-5p promoted cell proliferation, migration and tube formation while inhibited apoptosis in vitro and ameliorated the development of HICH in vivo. RBM24 is a direct target of miR-20a-5p and silencing RBM24 could partially recovery the development of HICH caused by miR-20a-5p inhibition both in vivo and in vitro. miR-20a-5p regulated the development of HICH depending on HIF1α/VEGFA pathway. Conclusion: Our results demonstrated that miR-20a-5p/RBM24 axis regulated hypertensive intracerebral hemorrhage via regulating HIF1α/VEGFA signaling pathway, in support of further investigation into miR-20a-5p therapies for HICH treatment.

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Section: Discussionmentioning

confidence: 99%

miR-20a-5p/RBM24 Axis Alleviated Hypertensive Intracerebral Hemorrhage via Regulating HIF1α/VEGFA Signaling Pathway

Xu¹,

Mo²,

Lü³

et al. 2021

Preprint

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“…We adopted a validated CAA-SVD scoring reflexive of total CAA pathological burden in the brain ( 4 , 20 ). Briefly, each marker category was scored on a 0–6 scale.…”

Section: Methodsmentioning

confidence: 99%

“…One point (each) was scored for ≥ 20 BG PVSEs or ≥ 5 lacunes. C 2 score was equivalent to the global cerebral SVD score developed to represent total SVD burden of both HA and CAA pathologies ( 20 ).…”

Section: Methodsmentioning

confidence: 99%

“…Although SVD changes are commonly seen in routine MRIs, little is known about their cognitive contributions in patients with multiple lobar CMBs. We used a validated CAA-SVD scoring system, showing close association with the severity of CAA-related vasculopathic changes at autopsy, to represent the underlying CAA load in the brain in our cohort ( 4 , 20 ). Additionally, we developed two comparable ordinal scores based on the four established MRI markers of SVD to compile the overall brain burden.…”

Section: Introductionmentioning

confidence: 99%

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Imaging Markers of Subcortical Vascular Dementia in Patients With Multiple-Lobar Cerebral Microbleeds

et al. 2021

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Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden.Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia.Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C1 scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C2 scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia.Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load.

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“…It was pointed out, in an accompanying editorial, 123 that lobar CMBs and presence of the APOE e4 allele were also associated with delayed dementia. Pasi et al 124 reported an enhanced risk of cognitive decline, following ICH, was associated with a higher global cerebral SVD score.…”

Section: White Matter Degenerationmentioning

confidence: 99%

Emerging Concepts in Vascular Dementia: A Review

Bir

Khan

Javalkar

et al. 2021

Journal of Stroke and Cerebrovascular Diseases

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Objective: Vascular dementia (VaD) is the second most common cause of dementia and a major health concern worldwide. A comprehensive review on VaD is warranted for better understanding and guidance for the practitioner. We provide an updated overview of the epidemiology, pathophysiological mechanisms, neuroimaging patterns as well as current diagnostic and therapeutic approaches. Materials and methods: A narrative review of current literature in VaD was performed based on publications from the database of PubMed, Scopus and Google Scholar up to January, 2021. Results: VaD can be the result of ischemic or hemorrhagic tissue injury in a particular region of the brain which translates into clinically significant cognitive impairment. For example, a cerebral infarct in the speech area of the dominant hemisphere would translate into clinically significant impairment as would involvement of projection pathways such as the arcuate fasciculus. Specific involvement of the angular gyrus of the dominant hemisphere, with resultant Gerstman's syndrome, could have a pronounced effect on functional ability despite being termed a "minor stroke". Small vessel cerebrovascular disease can have a cumulate effect on cognitive function over time. It is unfortunately well recognized that "good" functional recovery in acute ischemic or haemorrhagic stroke, including subarachnoid haemorrhage, does not necessarily translate into good cognitive recovery. The victim may often be left unable to have gainful employment, drive a car safely or handle their affairs independently. Conclusions: This review should serve as a compendium of updated information on VaD and provide guidance in terms of newer diagnostic and potential therapeutic approaches.

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Association of Cerebral Small Vessel Disease and Cognitive Decline After Intracerebral Hemorrhage

Cited by 69 publications

References 30 publications

miR-20a-5p/RBM24 Axis Alleviated Hypertensive Intracerebral Hemorrhage via Regulating HIF1α/VEGFA Signaling Pathway

miR-20a-5p/RBM24 Axis Alleviated Hypertensive Intracerebral Hemorrhage via Regulating HIF1α/VEGFA Signaling Pathway

Imaging Markers of Subcortical Vascular Dementia in Patients With Multiple-Lobar Cerebral Microbleeds

Emerging Concepts in Vascular Dementia: A Review

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