Atorvastatin for Mild Cognitive Impairment
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Johns Hopkins University
Must not be taking: Statins, Cyclosporine
Disqualifiers: Dementia, Substance abuse, Stroke, others
No Placebo Group
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?
The purpose of this study is to evaluate the effect of atorvastatin on brain vessel reactivity and with it on blood flow in people with mild cognitive impairment.
Will I have to stop taking my current medications?
The trial requires that you have not taken statins in the last 6 months, but it does not specify about other medications. If you are currently taking a statin, you would need to stop and wait for 6 months before participating.
What data supports the effectiveness of the drug Atorvastatin for mild cognitive impairment?
Research suggests that atorvastatin, a drug used to lower cholesterol, may help improve memory and thinking skills in people with Alzheimer's disease, which is a more severe form of cognitive decline. Additionally, statins, including atorvastatin, have been linked to delaying cognitive decline and dementia in people with mild cognitive impairment.12345
Is atorvastatin safe for humans?
Atorvastatin is generally considered safe and well-tolerated in humans, with extensive data showing it has a low incidence of side effects. However, there have been some reports of cognitive impairment in a few individuals taking statins, including atorvastatin, though this is not a common effect.15678
How does the drug Atorvastatin differ from other treatments for mild cognitive impairment?
Eligibility Criteria
This trial is for people with mild cognitive impairment who have memory or other cognitive issues not caused by another neurological disease. Participants should not be diagnosed with dementia, currently taking statins, or have taken them in the last six months. They must also be able to undergo MRI scans.Inclusion Criteria
Not demented by history.
I haven't taken statins in the last 6 months.
Your cognitive test scores for memory, processing speed, executive function, and language are very low (more than 1.5 standard deviations below normal for your age and education).
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Exclusion Criteria
You have been diagnosed with dementia in the past or have a history of dementia.
I am a transplant patient on cyclosporine.
I have not had a stroke or heart attack in the last 6 months.
See 5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phone screen
Treatment
Participants receive 40 mg atorvastatin orally daily in the evening for 12 weeks
12 weeks
Baseline visit, regular follow-up visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Atorvastatin (Statins)
Trial OverviewThe study tests if Atorvastatin, a medication typically used to lower cholesterol, can improve how well blood vessels in the brain respond and thus potentially increase blood flow in individuals with mild cognitive impairment.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Atorvastatin 40 mgExperimental Treatment1 Intervention
Participants receive 40 mg atorvastatin orally daily in the evening.
Atorvastatin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Lipitor for:
- Hypercholesterolemia
- Mixed dyslipidemia
- Homozygous familial hypercholesterolemia
🇺🇸 Approved in United States as Lipitor for:
- Hypercholesterolemia
- Mixed dyslipidemia
- Homozygous familial hypercholesterolemia
- Prevention of cardiovascular disease
🇨🇦 Approved in Canada as Lipitor for:
- Hypercholesterolemia
- Mixed dyslipidemia
- Homozygous familial hypercholesterolemia
- Prevention of cardiovascular disease
🇯🇵 Approved in Japan as Lipitor for:
- Hypercholesterolemia
- Mixed dyslipidemia
- Homozygous familial hypercholesterolemia
🇨🇳 Approved in China as Lipitor for:
- Hypercholesterolemia
- Mixed dyslipidemia
- Homozygous familial hypercholesterolemia
🇨🇭 Approved in Switzerland as Lipitor for:
- Hypercholesterolemia
- Mixed dyslipidemia
- Homozygous familial hypercholesterolemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins University, Bayview Medical CenterBaltimore, MD
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Who Is Running the Clinical Trial?
Johns Hopkins UniversityLead Sponsor
The Richman Family Precision Medicine Center of Excellence in Alzheimer DiseaseCollaborator
References
Statin therapy in Alzheimer's disease. [2015]Previous studies have suggested that statin therapy may be of benefit in treating Alzheimer's disease (AD). We initiated a double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to once-daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo among individuals with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score of 12-28]. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of most other medications in the treatment of co-morbidities. We demonstrated that atorvastatin treatment produced significantly (P = 0.003) improved performance on cognition and memory after 6 months of treatment (ADAS-cog) among patients with mild-to-moderate AD. This superior effect persisted at 1 year (P = 0.055). This positive effect on the ADAS-cog performance after 6 months of treatment was more prominent among individuals entering the trial with higher MMSE scores (P = 0.054). Benefit on other clinical measures was identified in the atorvastatin-treated population compared with placebo. Accordingly, atorvastatin therapy may be of benefit in the treatment of mild-to-moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment. Evidence also suggests that atorvastatin may slow the progression of mild-to-moderate AD, thereby prolonging the quality of an afflicted individual's life.
Statins, risk of dementia, and cognitive function: secondary analysis of the ginkgo evaluation of memory study. [2022]Lipid-lowering medications (LLMs) and especially statin drugs can delay cognitive decline and dementia onset in individuals with and without mild cognitive impairment (MCI) at baseline.
Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. [2022]Statin use and serum cholesterol reduction have been proposed as preventions for dementia and mild cognitive impairment (MCI).
The Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe): design and baseline characteristics. [2018]Growing evidence suggests that elevated cholesterol levels in mid-life are associated with increased risk of developing Alzheimer's disease (AD), and that statins might have a protective effect against AD and dementia. The Lipitor's Effect in Alzheimer's Dementia (LEADe) study tests the hypothesis that a statin (atorvastatin 80 mg daily) will provide a benefit on the course of mild to moderate AD in patients receiving background therapy of a cholinesterase inhibitor (donepezil 10 mg daily).
Systematic review of atorvastatin for the treatment of Alzheimer's disease. [2020]To assess the clinical efficacy and safety of atorvastatin in the treatment of Alzheimer's disease.
Cognitive impairment associated with atorvastatin and simvastatin. [2022]Clinical guidelines for cholesterol testing and management have been updated recently. With the evolving recognition of benefits and intensified recommendations for cholesterol management, many more patients will require cholesterol-lowering drugs. All the statins share similar adverse-effect profiles, with a low overall frequency of undesirable effects. Emerging data associate statins with a decreased risk of Alzheimer's disease; however, we report two women who experienced significant cognitive impairment temporally related to statin therapy. One woman took atorvastatin, and the other first took atorvastatin, then was rechallenged with simvastatin. Clinicians should be aware of cognitive impairment and dementia as potential adverse effects associated with statin therapy.
Atorvastatin: a safety and tolerability profile. [2021]Extensive data are available on the safety of atorvastatin from randomised clinical trials, postmarketing analyses and reports to regulatory agencies. Atorvastatin is generally well tolerated across the range of therapeutic dosages, with the exception of a slightly higher rate of liver enzyme elevations with atorvastatin 80 mg/day which does not appear to confer an increased risk of clinically important adverse events. Unlike simvastatin, atorvastatin is associated with a low incidence of muscular toxicity. It is not associated with neurological, cognitive or renal adverse effects and does not require dosage adjustment in patients with renal dysfunction, due to its favourable pharmacokinetic profile, which is unique among the statins. In patients aged > or =65 years, atorvastatin is well tolerated with no dose-dependent increase in adverse events up to the maximum daily dosage of 80 mg/day. Thus, atorvastatin is a safe and well tolerated statin for use in a wide range of patients.
Are statins protective or harmful to cognitive function? [2017]In February 2012, the FDA issued safety label changes and monitoring requirements for statin therapy. A risk of cognitive impairment was noted, although evidence was largely based on observational data, including case reports. In 2014, the National Lipid Association's safety task force found that evidence does not support cognitive decline as a classwide effect for statins. Some evidence has shown that statins may actually have beneficial effects on cognition. This article discusses management of statin therapy in patients with cardiovascular risk who may experience cognitive decline or have cognitive impairment, such as Alzheimer disease.
Atorvastatin. [2019]Atorvastatin (Lipitor, Pfizer) is a safe and effective 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitor (statin). It is the most potent currently available statin in terms of lowering low-density lipoprotein (LDL) and total cholesterol levels. It was the first statin shown to lower triglycerides in patients with isolated hypertriglyceridaemia. It has a good safety profile. In common with other statins, it has non-lipid-lowering effects including improving endothelial function, antiproliferative actions on smooth muscle and reducing platelet aggregation. It also has anti-inflammatory effects and may reduce plasma glucose levels. Clinical trial evidence with this statin is currently limited. It did slightly reduce events in the AVERT trial comparing patients receiving coronary angioplasty with those receiving high-dose atorvastatin therapy and in the MIRACL study reduced ischemia in patients with acute coronary syndromes. Other end point trials are in progress.
Atorvastatin mitigates memory deficits and brain monocyte infiltration in chronic hypercholesterolemia. [2023]Mild cognitive impairment (MCI) is a common symptom observed in people over 60 years old and is found to be aggravated by hypercholesterolemia. Severe neuroinflammation induced by BBB dysfunction and monocyte infiltration might be responsible for neuron damage and cognitive impairment. Atorvastatin is a lipid-lowering drug that is widely applied for the treatment of cardiovascular diseases. However, the potential function of Atorvastatin in hypercholesterolemia-induced MCI remains uncertain. Our research will explore the potential therapeutic function of Atorvastatin in memory deficits induced by chronic hypercholesterolemia. ApoE-/- mice were utilized to mimic the state of chronic hypercholesterolemia and were divided into four groups. Animals in the WT and ApoE-/-groups were orally administered with normal saline, while WT mice in the Atorvastatin group and ApoE-/- mice in the ApoE-/-+ Atorvastatin group were orally administered with 10 mg/kg/day Atorvastatin. Markedly increased plasma cholesterol levels reduced RI in the long-term memory test and the spatial short-term memory test, declined mobility in the open field test, and downregulated PSD-95 and BDNF were observed in ApoE-/- mice, all of which were signally reversed by Atorvastatin. Moreover, the percentages of brain Ly6Chi CD45+ cells and CD3+ CD45+ cells, as well as the blood Ly6Chi CD45+ cells, plasma IL-12/IL-23 levels and IL-17 level were found notably increased in ApoE-/- mice, all of which were largely repressed by Atorvastatin. Lastly, the increased BBB permeability, decreased ZO-1 and occludin levels, and reduced KLF2 level were markedly abolished by Atorvastatin. Collectively, Atorvastatin mitigated memory deficits and brain monocyte infiltration in ApoE-/- mice.