Statins for the treatment of dementia

Department of Geriatric Medicine, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast, UK, BT9 7BL.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 07/2010; 4(8):CD007514. DOI: 10.1002/14651858.CD007514.pub2
Source: PubMed


Background High levels of cholesterol (a fatty substance known as a lipid) in the blood are thought to contribute to the cause of Alzheimer's disease and vascular dementia. The statin family of medications (lovastatin, pravastatin, simvastatin and others) are powerful cholesterol-lowering medications and are first-line treatments for reducing cholesterol in people with, or at risk of, cardiovascular disease. There has been much interest in the possible role of statins in the treatment of dementia. Study characteristics Two independent authors searched scientific databases for studies in which a statin or a placebo (a pretend treatment) was given for at least six months. We included people with a probable or possible diagnosis of Alzheimer's disease according to standard clinical criteria. The findings were current to January 2014. Key results We identified four studies involving 1154 participants (age range 50 to 90 years). The studies used standard tests to assess the severity of Alzheimer's disease. From these trials, including two large trials, we found no evidence that statins help in the treatment of cognitive decline in dementia. Quality of the evidence The quality of evidence is felt to be high as two large randomised controlled trials have been included along with two smaller ones.

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Available from: Reem Malouf, Sep 30, 2015
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    • "Recent evidence indicates that prevalence of dementia is low among patients taking statins over a long period of time [15] [16] [17]. Contrary to this, there are clinical reports indicating that statins lead to cognitive impairment [18] [19] [20]. "
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    ABSTRACT: Objectives. Aluminium, a neurotoxic agent in humans, has been implicated in the pathogenesis of neurodegenerative disorders. In this study, we examined the behavioral and biochemical effects of aluminium in rats with special emphasis on memory centres, namely, hippocampus and frontal cortex. Further, the effect of simvastatin treatment on aluminium intoxication was evaluated. Methods. Rats were exposed to aluminium chloride (AlCl 3) for 60 days. Simvastatin (10 mg/kg/p.o.) and rivastigmine (1 mg/kg/p.o.) were administered daily prior to AlCl 3 . Behavioral parameters were assessed using Morris water maze test and actophotometer followed by biochemical investigations, namely, acetylcholinesterase (AChE) activity, TNF-í µí»¼ level, antioxidant enzymes (GSH, catalase), lipid peroxidation, and nitrite level in hippocampus and frontal cortex. Triglycerides, total cholesterol, LDL, and HDL levels in serum were also determined. Key Findings. Simvastatin treatment improved cognitive function and locomotor activity in rats. Simvastatin reversed hyperlipidemia and significantly rectified the deleterious effect of AlCl 3 on AChE activity. Further, in hippocampus and frontal cortex, aluminium-induced elevation in nitrite and TNF-í µí»¼ and reduction in antioxidant enzymes were inhibited by simvastatin. Conclusion. To conclude, the present study suggests that simvastatin per se protects the neurons in hippocampus and frontal cortex from AlCl 3 , an environmental toxin.
    Behavioural neurology 02/2015; 2015(1):1-9. · 1.45 Impact Factor
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    • "Recently, statins have also been proposed for treatment and prevention of AD due to the association of this disease with altered cholesterol metabolism [4] [5]. However, epidemiological and experimental studies that have examined the beneficial effects of statins for AD prevention have yielded conflicting results [6] [7] In fact, recent studies have reported deleterious effects of several statins on neuronal function both, in vivo and in vitro [8] [9] [10] [11] [12]. "
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    ABSTRACT: In view that several studies have shown a positive correlation between high cholesterol and an increase in the risk for developing Alzheimer's disease (AD) statins have been proposed as alternative drugs for its treatment and/or prevention. However, the potential benefits of statins remain controversial. Although they have lipid-lowering properties, statins also have pleiotropic effects that are unrelated to cholesterol reduction and have a wide range of biological implications whose consequences in brain function have not been fully characterized. In this work we analyze different studies that have reported both, beneficial and toxic effects for statins in the central nervous system (CNS), and we revise the literature that claims their potential for treating AD. First, we present an overview of the cholesterol metabolism and its regulation in the brain in order to provide the framework for understanding the pathological association between altered cholesterol and AD. Then, we describe the cholesterol-lowering and pleiotropic properties of statins that have been reported in vivo and in in vitro models. We conclude that the effects of statins in the brain are broad and complex and that their use for treating several diseases including AD should be carefully analyzed given their multiple and broad effects.
    Current Alzheimer Research 10/2014; 11(9). DOI:10.2174/1567205011666141001114858 · 3.89 Impact Factor
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    • "Data from animal models studies suggest possible mechanisms underlying the beneficial role of atorvastatin in preventing AD, including the reduction of Ab [4], b-secretase (BACE1) protein levels [5] and oxidative stress [6]. However, the importance of statin treatment in AD is still under debate, given that some randomized clinical trials did not show any significant benefit on cognition as reviewed by [7] [8]. In particular, the concerns regarding the mechanism of action by which statins mediate their potentially beneficial effects remain to be fully clarified. "
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    ABSTRACT: Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment, inability to perform activities of daily living and mood changes. Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including AD. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. The aim of this review is to provide an overview on the new discoveries about the effects of statin therapy on the oxidative ad nitrosative stress levels as well as on the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system in the brain. We propose a novel mechanism of action for atorvastatin which, through the activation of HO/BVR-A system, may contribute to the neuroprotective effects thus suggesting a potential therapeutic role in AD and potentially accounting for the observation of decreased AD incidence with persons on statin.
    Biochemical pharmacology 11/2013; 88(4). DOI:10.1016/j.bcp.2013.10.030 · 5.01 Impact Factor
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