Cochrane review on ‘Statins for the treatment of dementia’

McGuinness, Bernadette; O’Hare, J.; Craig, David; Bullock, Roger; Malouf, Reem; Passmore, Peter

doi:10.1002/gps.3797

Cited by 66 publications

(48 citation statements)

References 79 publications

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“…Whereas the psychometric changes in the placebo arm are in keeping with observed changes reported elsewhere in similar populations, 28,29 the change in ADAS-cog was double than anticipated. 4 While every attempt was made to improve internal validity by ensuring raters received the same psychometric rating training and, wherever possible, not change between visits, small numbers in the study cannot rule out the random allocation of a more rapidly declining group to the placebo arm and differences between groups should be viewed with caution.…”

Section: (1) 4 (3)supporting

confidence: 72%

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial

2015

Neurology

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Objectives: To determine whether the tumor necrosis factor a inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. Methods:In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353).Results: Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n 5 20) or placebo (n 5 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function.Conclusions: This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. Classification of evidence:This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia. Neurology ® 2015;84:2161-2168 GLOSSARY AD 5 Alzheimer disease; ADAS-cog 5 Alzheimer's Disease Assessment Scale-cognitive; BADLS 5 Bristol Activities of Daily Living Scale; CGI-I 5 Clinical Global Impression-Improvement; CI 5 confidence interval; CRP 5 C-reactive protein; IL 5 interleukin; IQR 5 interquartile range; ITT-LOCF 5 intention to treat-last observation carried forward; NPI 5 Neuropsychiatric Inventory; RPCT 5 randomized placebo-controlled trial; sMMSE 5 standardized Mini-Mental State Examination; TNFa 5 tumor necrosis factor a.Acute and chronic systemic inflammation is characterized by the production of proinflammatory cytokines including tumor necrosis factor a (TNF-a) from immune cells. TNF-a has a role in systemic immune-to-brain communication by activating the central immune response.1 In humans, low levels of chronic systemic inflammation are associated with evidence of microglial activation.2 In animals, experimentally induced acute systemic inflammation results in an exaggerated central immune response leading to exacerbated neurodegeneration. 3 In participants with Alzheimer disease (AD) dementia, we have shown that modestly increased serum TNF-a levels are associated with an increased rate of cognitive decline 4 and an exaggeration of neuropsychiatric symptoms. Peer-reviewed published data on the use of the TNF-a inhibitor etanercept in AD dementia is limited to small open-l...

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Section: (1) 4 (3)supporting

confidence: 72%

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial

2015

Neurology

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“…Since 2012, systematic reviews [5,[29][30][31] and narrative reviews [32][33][34][35] have repeatedly reported a lack of conclusive evidence that statins cause cognitive impairment. A Cochrane review in 2013 found that a mean reduction in LDL-C by 22 % was not associated with worsening of cognitive function [36].…”

Section: The Statin Experiencementioning

confidence: 99%

PCSK9 Inhibitors and Neurocognitive Adverse Events: Exploring the FDA Directive and a Proposal for N-of-1 Trials

Swiger¹,

Martin²

2015

Drug Saf

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“…There is also evidence of a mechanism for reduction of cholesterol levels in the brain that leads to reduction of NFTs and some pleiotropic effects attributed to anti-inflammatory properties. 20,45 Use of statins may be an important adjunct in treating AD. Some physicians have advocated their use as a preventive measure for patients who have a dementia risk profile mediated by cerebral vasculature.…”

Section: Tamibarotenementioning

confidence: 99%

“…Furthermore, it needs to be borne in mind that statins have a risky safety profile and there may be hepatic impairment and risk of rhabdomyolysis at doses that would be effective for continuous treatment of AD. 18,20 In a meta-analysis on separately evaluated cross-sectional and longitudinal observational studies (total of 19), the crosssectional studies showed that statins had a protective effect, and it was noted that use of statins was associated with a reduced risk of developing AD and other forms of dementia. However, progress in such studies is still restricted by bias in some of them.…”

Section: Tamibarotenementioning

confidence: 99%

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Perspectives for treating Alzheimer's disease: a review on promising pharmacological substances

et al. 2016

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CONTEXT AND OBJECTIVE: Dementia is a syndrome characterized by functional and cognitive decline. Alzheimer's disease (AD) is one of the most common causes of dementia and has high prevalence among the elderly. It is known that there is no drug capable of interfering with the course of the disease. Research on treatments for AD has been marked by the appearance of new drugs and their abandonment. This study aimed to describe drugs that have been studied with regard to treating AD and which are capable of influencing the course of the disease. DESIGN AND SETTING: Narrative review on original articles published worldwide. METHODS: A systematized search was conducted in the PubMed/MEDLINE, Cochrane Library/Cochrane and SciELO/Bireme databases. The descriptors "Molecular Mechanisms of Pharmacological Action" and "Drug Therapy" were each combined with the descriptor "Alzheimer disease". All of these can be found in MeSH and DeCS. These descriptors were used alone or in combination, and a filter specifying publication between January 2009 and October 2015 in English, Spanish or Portuguese was set. RESULTS: 6,888 articles were found, of which 37 were included in this review; 70.3% of the articles selected were of good quality with low or unclear risk of bias. 86 drugs were considered promising for AD treatment and these were classified into 20 pharmacological categories. CONCLUSION: There are no drugs capable of influencing the course of AD such that treatments are safe and effective. However, immunomodulators stood out as promising, given their effectiveness and quality in the articles analyzed. RESUMO CONTEXTO E OBJETIVO:A demência é uma síndrome caracterizada por declínio funcional e cognitivo, sendo a doença de Alzheimer (DA) uma das causas mais comuns e de alta prevalência em idosos. Sabe-se que não há medicamento capaz de interferir no curso da doença e as pesquisas para o tratamento da DA têm sido marcadas pelo surgimento e abandono de novas drogas. O objetivo deste estudo foi descrever as drogas capazes de influenciar o curso da DA que têm sido estudadas para o tratamento da doença.

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Cochrane review on ‘Statins for the treatment of dementia’

Abstract: There is insufficient evidence to recommend statins for the treatment of dementia.

Cited by 66 publications

References 79 publications

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial

PCSK9 Inhibitors and Neurocognitive Adverse Events: Exploring the FDA Directive and a Proposal for N-of-1 Trials

Perspectives for treating Alzheimer's disease: a review on promising pharmacological substances

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