Longitudinal Study on Low-Dose Aspirin versus Placebo Administration in Silent Brain Infarcts: The Silence Study

Maestrini, Ilaria; Altieri, Marta; Clemente, Laura Di; Vicenzini, Edoardo; Pantano, Patrizia; Raz, Eytan; Silvestrini, Mauro; Provinciali, Leandro; Paolino, Isabella; Marini, Carmine; Giuseppe, Matteo Di; Russo, Tommasina; Federico, Francesco; Coppola, Cristiana; Prontera, Maria Pia; Mezzapesa, Domenico Maria; Lucivero, V.; Parnetti, Lucilla; Sarchielli, Paola; Peducci, Maria; Inzitari, Domenico; Carlucci, Giovanna; Serrati, Carlo; Zat, Carla; Cavallini, Anna; Persico, Alessandra; Micieli, Giuseppe; Bastianello, Stefano; Piero, Vittorio Di

doi:10.1155/2018/7532403

Cited by 15 publications

(18 citation statements)

References 32 publications

(45 reference statements)

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“…An increased number of infarct-like lesions as detected by MRI at the end of the study was seen in 16 subjects in the control group and two in the cilostazol group. 65 The two identified studies 64,65 are both small and even though a tendency to better clinical outcomes was seen in both studies, they provide insufficient support for a general recommendation of antiplatelet treatment in subjects with ccSVD to avoid new clinical events (Table 5), which only includes the study by Maestrini et al 64 because we did not consider the study of patient with diabetes mellitus by Shinoda-Tagawa et al 65 to be a "true" primary prevention study.…”

Section: Cilostazol Vs No Antithrombotic Treatmentmentioning

confidence: 96%

“…One randomised, double blind placebo-controlled trial included patients !45 years with at least one silent brain infarct (SBI) but no previous clinical cerebrovascular events for randomization to aspirin 100 mg (n¼36) or placebo (n¼47). 64 The primary endpoint was the combined endpoint of ischaemic stroke, TIA, and new silent brain infarcts (SBIs) detected at MRI which had occurred in nine controls (19.1%) and two ). Findings should be interpreted with care as the number of incident ischaemic strokes and myocardial infarctions were small with wide confidence intervals including one.…”

Section: Aspirin Vs Placebomentioning

confidence: 99%

“…We identified one study in patients with ccSVD ( Figure 3 , Table 4 ), 64 and a second study in a population that can be considered at high risk for ccSVD, where antiplatelet therapy was trialled for preventing the specified clinical outcomes defined in this guideline document. 64 , 65 Pooling was not possible, therefore we describe each study and the PICO outcome that is addressed.…”

Section: Analysis Of Current Evidencementioning

confidence: 99%

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ESO Guideline on covert cerebral small vessel disease

Wardlaw

Debette

Jokinen

et al. 2021

European Stroke Journal

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‘Covert’ cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD.

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Section: Cilostazol Vs No Antithrombotic Treatmentmentioning

confidence: 96%

Section: Aspirin Vs Placebomentioning

confidence: 99%

Section: Analysis Of Current Evidencementioning

confidence: 99%

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ESO Guideline on covert cerebral small vessel disease

Wardlaw

Debette

Jokinen

et al. 2021

European Stroke Journal

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“…A variety of nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to reduce the incidence of AD and other neurodegenerative disorders in prospective trials and in model organisms (Vlad et al, 2008;Varvel et al, 2009;Tasaki et al, 2012;Zhang et al, 2018). The same studies also found NSAIDs protect against cardiovascular and cerebrovascular disease (Patrono, 2013;Maestrini et al, 2018) and several types of adult-onset cancer (Di Francesco et al, 2015). Other, non-pharmacological strategies commonly employed to reduce the risk of AD include supplementation of polyunsaturated, ω-3 fatty acids (Lim et al, 2005), physical activity (Roach et al, 2011), and cognitive engagement (Maci et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer’s Disease

Kakraba

Ayyadevara

Penthala

et al. 2019

Front. Mol. Neurosci.

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Age-progressive neurodegenerative pathologies, including Alzheimer's disease (AD), are distinguished and diagnosed by disease-specific components of intra-or extracellular aggregates. Increasing evidence suggests that neuroinflammation promotes protein aggregation, and is involved in the etiology of neurological diseases. We synthesized and tested analogs of the naturally occurring tubulin-binding compound, combretastatin A-4. One such analog, PNR502, markedly reduced the quantity of Alzheimer-associated amyloid aggregates in the BRI-Aβ 1-42 mouse model of AD, while blunting the ability of the pro-inflammatory cytokine IL-1β to raise levels of amyloid plaque and its protein precursors in a neuronal cell-culture model. In transgenic Caenorhabditis elegans (C. elegans) strains that express human Aβ 1-42 in muscle or neurons, PNR502 rescued Aβ-induced disruption of motility (3.8-fold, P < 0.0001) or chemotaxis (1.8-fold, P < 0.05), respectively. Moreover, in C. elegans with neuronal expression of Aβ 1-42 , a single day of PNR502 exposure reverses the chemotaxis deficit by 54% (P < 0.01), actually exceeding the protection from longer exposure. Moreover, continuous PNR502 treatment extends nematode lifespan 23% (P ≤ 0.001). Given that PNR502 can slow, prevent, or reverse Alzheimer-like protein aggregation in human-cell-culture and animal models, and that its principal predicted and observed binding targets are proteins previously implicated in Alzheimer's, we propose that PNR502 has therapeutic potential to inhibit cerebral Aβ 1-42 aggregation and prevent or reverse neurodegeneration.

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“…Epidemiological studies have shown that patients with silent brain infarction have a higher risk of future stroke. Al- though the effectiveness of aspirin to prevent stroke has not been studied in this setting [9], a recent prospectively multicenter clinical trial has shown that silent cerebral infarction seems to be a negative prognostic factor and low-dose aspirin treatment might improve the prognosis [10]. Therefore, it seems appropriate to apply secondary stroke prevention strategies to silent stroke patients with modifiable risk factors for atherosclerosis.…”

Section: Case Reportmentioning

confidence: 99%

An Uncommon Silent Strategic Left Middle Cerebral Artery Infarction

Dharmasaroja

2019

J Med Cases

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Impairment of memory retrieval is not the major presenting symptoms of vascular cognitive impairment (VCI), which can result from silent strokes occurring in uncommon vascular territories, and can be detected only on neuroimaging or neuropathology. The neuroanatomical substrate for VCI remains unclear. This report presents an uncommon location of silent strategic infarction resulting in an insidious onset and gradual progression of the cognitive decline without overt sensorimotor deficits.

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Longitudinal Study on Low-Dose Aspirin versus Placebo Administration in Silent Brain Infarcts: The Silence Study

Cited by 15 publications

References 32 publications

ESO Guideline on covert cerebral small vessel disease

ESO Guideline on covert cerebral small vessel disease

A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer’s Disease

An Uncommon Silent Strategic Left Middle Cerebral Artery Infarction

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