Atorvastatin for Mild Cognitive Impairment

Recruiting in Palo Alto (17 mi)

Overseen by Paul Rosenberg, MD

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. ^{1 2 3 4 5}

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. ^{1 5 6 7 8}

How does the drug Atorvastatin differ from other treatments for mild cognitive impairment?

Atorvastatin is unique because it is primarily a cholesterol-lowering drug that may also help with mild cognitive impairment by reducing inflammation and improving brain function, which is not the primary focus of other treatments for this condition. ^{1 3 4 9 10}

Research Team

Paul Rosenberg, MD

Principal Investigator

Johns Hopkins University

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).

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.

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 Overview The 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

Group I: Atorvastatin 40 mg Experimental Treatment 1 Intervention

Participants receive 40 mg atorvastatin orally daily in the evening.

Atorvastatin is already approved in Canada, Japan, China, Switzerland for the following indications:

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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

The Richman Family Precision Medicine Center of Excellence in Alzheimer Disease

Collaborator

Trials

1

Recruited

20+

Findings from Research

A 1-year double-blind, placebo-controlled trial with 80 mg of atorvastatin daily showed significant cognitive and memory improvements in patients with mild-to-moderate Alzheimer's disease after 6 months, with a continued positive trend at 1 year.

The benefits of atorvastatin were more pronounced in patients who had higher baseline cognitive function, suggesting that earlier treatment may enhance its effectiveness in slowing the progression of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin therapy in Alzheimer's disease. Sparks, DL., Sabbagh, M., Connor, D., et al.[2015]

In a study of 3069 cognitively healthy elderly patients aged 75 and older, the use of statins was linked to a reduced risk of developing all-cause dementia and Alzheimer's disease, suggesting a protective effect against cognitive decline.

However, the same protective effect was not observed in individuals with mild cognitive impairment (MCI) at baseline, indicating that statins may be more beneficial for those without existing cognitive issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statins, risk of dementia, and cognitive function: secondary analysis of the ginkgo evaluation of memory study. Bettermann, K., Arnold, AM., Williamson, J., et al.[2022]

Statin use is associated with a significantly lower risk of developing dementia, with statin users having a two- to threefold reduced risk compared to non-users, independent of serum cholesterol levels, based on a study of 1604 participants followed for about 25 years.

Higher total cholesterol levels at the first visit were linked to a reduced risk of mild cognitive impairment (MCI), while a decline in total cholesterol was associated with increased dementia risk in men, suggesting complex relationships between cholesterol levels and cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. Beydoun, MA., Beason-Held, LL., Kitner-Triolo, MH., et al.[2022]

The LEADe study, involving 641 participants with mild to moderate Alzheimer's disease, is investigating the effects of atorvastatin (80 mg daily) on cognitive decline while patients are also receiving donepezil, a common Alzheimer's treatment.

This study aims to determine if atorvastatin can improve cognitive function and brain volume in Alzheimer's patients, potentially highlighting a protective role of statins against Alzheimer's disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe): design and baseline characteristics. Jones, RW., Kivipelto, M., Feldman, H., et al.[2018]

Atorvastatin did not show any significant clinical benefits in improving cognitive function or overall condition in patients with mild to moderate Alzheimer's disease, based on a review of two randomized controlled trials involving 710 participants.

The treatment group experienced higher rates of adverse effects, including abnormal liver function and withdrawal from treatment, indicating potential safety concerns associated with atorvastatin use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of atorvastatin for the treatment of Alzheimer's disease. Sun, Y., Wang, G., Pan, Z., et al.[2020]

Atorvastatin is generally well tolerated across various dosages, with only a slight increase in liver enzyme elevations at the highest dose (80 mg/day), but no significant risk of serious adverse events.

Unlike some other statins, atorvastatin has a low incidence of muscular toxicity and does not require dosage adjustments for patients with renal dysfunction, making it a safe option for older adults (65 years and older) as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: a safety and tolerability profile. Arca, M.[2021]

Atorvastatin is a highly effective statin that significantly lowers LDL and total cholesterol levels, and it is the first statin proven to reduce triglycerides in patients with high triglyceride levels.

In addition to its cholesterol-lowering effects, atorvastatin has beneficial non-lipid effects, such as improving blood vessel function and reducing inflammation, although clinical trial evidence is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin. Wierzbicki, AS.[2019]

Atorvastatin, a lipid-lowering drug, significantly improved memory deficits and reduced neuroinflammation in ApoE-/- mice, which were used to model chronic hypercholesterolemia, suggesting its potential therapeutic role in mild cognitive impairment (MCI) associated with high cholesterol.

The treatment with Atorvastatin not only reversed cognitive impairments but also decreased brain monocyte infiltration and improved blood-brain barrier (BBB) integrity, indicating a protective mechanism against neuron damage in the context of hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin mitigates memory deficits and brain monocyte infiltration in chronic hypercholesterolemia. Gong, F., Shi, Q., Mou, X., et al.[2023]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Statin therapy in Alzheimer's disease. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Statins, risk of dementia, and cognitive function: secondary analysis of the ginkgo evaluation of memory study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The Atorvastatin/Donepezil in Alzheimer's Disease Study (LEADe): design and baseline characteristics. [2018]

5. India pubmed.ncbi.nlm.nih.gov

Systematic review of atorvastatin for the treatment of Alzheimer's disease. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Cognitive impairment associated with atorvastatin and simvastatin. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Atorvastatin: a safety and tolerability profile. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Are statins protective or harmful to cognitive function? [2017]

9. England pubmed.ncbi.nlm.nih.gov

Atorvastatin. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Atorvastatin mitigates memory deficits and brain monocyte infiltration in chronic hypercholesterolemia. [2023]