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BACKGROUND AND PURPOSE: Prevention of ischaemic stroke and cardiovascular events is an established benefit of statin therapy, but the effects of statin treatment on the accrual of magnetic resonance imaging (MRI) markers of ischaemic cerebral injury remain unknown. A systematic review was performed to identify all studies that randomized patients with cardiovascular risk factors to statin treatment and assessed the effect of statin treatment on covert infarcts (asymptomatic, evident only on neuroimaging) and white matter hyperintensity (WMH) accrual on MRI. METHODS: A systematic review in MEDLINE and Scopus from inception to 23 October 2019 was performed. A random-effects model was used to calculate the pooled estimates of the crude risk ratios and standardized mean differences. RESULTS: Data from three randomized controlled trials (1430 participants) were included evaluating the effect of rosuvastatin (10 mg/day) in 668 hypertensive patients older than 60 years of age over 5 years, pravastatin (40 mg/day) in 554 elderly people more than 70 years of age over 3 years and simvastatin (20 mg/day) in 208 patients with asymptomatic middle cerebral artery stenosis over 2 years. Patients randomized to statin treatment had decreased accrual of new covert infarcts (risk ratio 0.63, 95% confidence interval 0.46-0.88) during a mean follow-up of 2-6 years. Only one study reported WMH decreased volume change in patients randomized to statin treatment compared to patients randomized to non-statin treatment (standardized mean difference -1.17; 95% confidence interval -1.33, -1.00). CONCLUSION: Our findings suggest that, in addition to stroke prevention, statin treatment can reduce the accrual of covert MRI markers of ischaemic cerebral injury.
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Isquemia Encefálica , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Infarto Cerebral , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.
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Isquemia Encefálica , Acidente Vascular Cerebral , Administração Intravenosa , Idoso , Isquemia Encefálica/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hemorragias Intracranianas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Terapia Trombolítica , Resultado do TratamentoRESUMO
Aims: To determine safety of intranasal insulin (INI) in MemAID trial participants with diabetes treated with systemic insulins. Materials and Methods: This randomized, double-blinded trial consisted of 24-week INI or placebo treatment once daily and 24-week follow-up. Safety outcomes were: 1) Short-term effects on glycemic variability, hypoglycemic episodes on continuous glucose monitoring (CGM) at baseline and on-treatment. 2) Long-term effects on glucose metabolism and weight on INI/placebo treatment and post-treatment follow-up. Of 86 screened subjects, 14 were randomized, 9 (5 INI, 4 Placebo) completed CGM at baseline and on-treatment, and 5 (2 INI, 3 Placebo) completed treatment and follow-up. Results: INI was safe and was not associated with serious adverse events, hypoglycemic episodes or weight gain. INI administration did not acutely affect capillary glucose. Glycemic variability on CGM decreased with INI, compared to baseline. On INI treatment, there was a long-term trend toward lower HbA1c, plasma glucose and insulin. No interactions with subcutaneous insulins were observed. Conclusions: INI is safe in older people with diabetes treated with systemic insulins, and it is not associated with adverse events, hypoglycemia or weight gain. Future studies are needed to determine whether INI administration can reduce glycemic variability, improve insulin sensitivity and thus potentially lessen diabetes burden in this population.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) accelerates brain aging and increases the risk for dementia. Insulin is a key neurotrophic factor in the brain, where it modulates energy metabolism, neurovascular coupling, and regeneration. Impaired insulin-mediated brain signaling and central insulin resistance may contribute to cognitive and functional decline in T2DM. Intranasal insulin (INI) has emerged as a potential therapy for treating T2DM-related cognitive impairment. METHODS/DESIGN: Ongoing from 2015, a prospective, two-center, randomized, double-blind, placebo-controlled trial of 210 subjects (120 T2DM and 90 non-diabetic older adults) randomized into four treatment arms (60 T2DM-INI, 60 T2DM-Placebo, 45 Control-INI, and 45 Control-Placebo) evaluating the long-term effects of daily intranasal administration of 40 International Units (IU) of human insulin, as compared to placebo (sterile saline) over 24 weeks and 24 weeks of post-treatment follow-up. Study outcomes are: 1) long-term INI effects on cognition, daily functionality, and gait speed; 2) identifying a clinically relevant phenotype that predicts response to INI therapy; 3) long-term safety. CONCLUSION: This study addresses an important knowledge gap about the long-term effects of intranasal insulin on memory and cognition in older people with T2DM and non-diabetic controls, and may provide a novel therapeutic target for prevention and treatment of cognitive and functional decline and dementia. Trial Registration NCT02415556.