Systematic review of the efficacy of statins for the treatment of Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is the most common type of dementia. Recent studies have assessed the possibility of using statins as treatment for AD. However, their effi cacy is not clear. In this study, we collected the most relevant information about the effi cacy of statins for the treatment of AD. We conducted a systematic literature search using MEDLINE, EMBASE and The Cochrane Library. We included clinical trials, meta-analyses and systematic reviews that analysed the effi cacy of statins in AD. We also extracted the characteristics and effi cacy results of the studies selected. Of the 304 articles identifi ed, 13 complied with the inclusion criteria. The scientifi c quality of studies was high and their results indicated that there were no signifi cant differences in the main effi cacy variables between statins and placebo treatment for AD. Therefore, according to the available scientifi c evidence, statins have not shown an improvement in cognition and do not appear to offer signifi cant benefi ts to patients with AD. KEYWORDS :Alzheimer's disease , statins , effi cacy , systematic review IntroductionAlzheimer's disease (AD) is the most common type of dementia. It is a neurodegenerative pathology, whose incidence has increased in the past few years. With an estimated prevalence of 46.8 million cases worldwide in 2015, the number of patients with AD is expected to continue to increase in the coming years. 1There are two main manifestations of AD: early-onset AD, which especially affects young people, and late-onset AD, which is more common and occurs mainly in older people, usually patients over 65 years old; therefore, ageing is considered to be the main risk factor for the disease. 3 When these deposits accumulate in the cerebral cortex, they cause neurotoxic effects. Aβ peptides derive from the amyloid precursor protein (APP) in response to the activity of secretases (α-SAPP, β-SAPP and γ-SAPP), which cleave the APP into different fragments. 4 These secretases have been the subject of scientific research because of their role in the regulation of Aβ.

Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

“…However, more recently the LEADe trial of 2010 and the CLASP study of 2011 that assessed the use of statins in AD patients found no net benefit or harm in terms of cognitive decline relative to the placebo group [180,181]. Further support for the idea that statins do not generally benefit AD patients comes from another systematic review [182]. These findings, however, contradict another large study of Medicare beneficiaries which established a beneficial association between statin use and reduced AD incidence in specific populations [183].…”

Association Between Previous Statin Use and Alzheimer’s Disease: A Nested Case-control Study Using a National Health Screening Cohort

“…In this analysis, the crude model, model 1 (adjusted for dyslipidemia history, total cholesterol, SBP, DBP, and fasting blood glucose), and model 2 (adjusted for model 1 plus obesity, smoking, alcohol consumption, and CCI scores) were determined. The analysis was strati ed by age, sex, income (lower income [1][2][3] and high income [4][5]), and region of residence.…”

“…Alzheimer's disease (AD) is not only the most common form of dementia but also the most common cause of neurodegenerative dementia among elderly individuals, accounting for approximately 60% or more of all people with dementia [1]. With an estimated prevalence of 46.8 million cases worldwide in 2015, the number of patients with AD is expected to continue to increase in the coming years [2]. This rapidly increasing disease burden is challenging healthcare and socioeconomic systems worldwide.…”

“…Statins are the most widely prescribed Food and Drug Administration (FDA)-approved cholesterollowering medications [4], and they are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that reduce cholesterol synthesis and upregulate low-density lipoprotein (LDL) receptors in hepatocyte membranes, enabling greater clearance of LDL from the bloodstream and lowering the level of lipoproteins [2]. Beyond their cholesterol-lowering effect, statins have demonstrated various additional effects, including antioxidant, anti-in ammatory, antithrombotic, anti-excitotoxicity, and angiogenesispromoting effects; the improvement of vascular endothelial function; and the modulation of amyloid and tau metabolism [5][6][7][8].…”

"Alzheimer’s dementia "

“…However, studies have shown that there was no significant difference in patients that used statins and those who used placebo. 2,5,7 General practitioner has an essential role in early detection of Alzheimer's disease, recognition of dementia symptoms,referring to diagnostics and specialist consultation, participation in treatment and follow-up of the disease, especially in organization of care and offering permanent help to the patients and support to the family in care of AD patients. He is a part of interdisciplinary team comprising experts of various work fields, specialist consultants, nurses, social workers, psychologists and other experts of various professional profile.…”