Atorvastatin for Mild Cognitive Impairment

Overseen By Ritu Agarwal

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Statins, Cyclosporine

Disqualifiers: Dementia, Substance abuse, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how atorvastatin, a common cholesterol-lowering medication, affects blood flow in the brain for individuals with mild cognitive impairment (MCI), a condition impacting memory and thinking skills. Researchers aim to determine if atorvastatin can improve brain vessel reactivity, potentially benefiting those with MCI. Participants will take a 40 mg dose of atorvastatin every evening. Suitable candidates include those with MCI who are not currently taking statins or have not taken them in the last six months. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that atorvastatin is likely to be safe for humans?

Research shows that atorvastatin is generally safe for use and is commonly prescribed to lower cholesterol. Regarding brain health, studies have produced mixed results. Some research suggests atorvastatin might aid memory and thinking. For instance, one study found it slightly improved memory after six months.

However, not all studies agree. Some link long-term or high doses to memory issues, such as forgetfulness. Overall, findings suggest atorvastatin usually doesn't cause memory problems in older adults. Prospective trial participants should know that atorvastatin is already approved for other uses, supporting its safety. Individual experiences can vary, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about atorvastatin for mild cognitive impairment because it brings a fresh approach to tackling this condition. Unlike most current treatments that focus on symptom management, atorvastatin, a cholesterol-lowering medication, may offer neuroprotective benefits by reducing inflammation and improving blood flow in the brain. This unique mechanism of action could slow cognitive decline, providing a new avenue of hope for those affected.

What evidence suggests that atorvastatin might be an effective treatment for mild cognitive impairment?

A study found that atorvastatin lowered the risk of dementia by about 11% in certain groups. Research shows that statins, like atorvastatin, might help slow memory and thinking problems. Additionally, using statins for each additional year can reduce the risk of dementia by 9%. However, some studies have found that long-term or high-dose statin use might cause memory issues. These findings are important to consider when evaluating atorvastatin for mild memory problems. Participants in this trial will receive 40 mg of atorvastatin daily to assess its effects on mild cognitive impairment. ^{1 3 6 7 8}

Who Is on the Research Team?

Paul Rosenberg, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin

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.

How Is the Trial Designed?

Group I: Atorvastatin 40 mg Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

The Richman Family Precision Medicine Center of Excellence in Alzheimer Disease

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

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]

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]

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 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]

The FDA acknowledged a potential risk of cognitive impairment associated with statin therapy in 2012, but this was primarily based on observational data rather than strong clinical evidence.

In 2014, the National Lipid Association concluded that there is no substantial evidence supporting cognitive decline as a common effect of statins, and some studies suggest that statins may even have positive effects on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are statins protective or harmful to cognitive function? Mospan, CM.[2017]

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]

Recent updates to clinical guidelines suggest that more patients will need cholesterol-lowering medications, particularly statins, which generally have a low frequency of adverse effects.

Despite emerging evidence linking statins to a reduced risk of Alzheimer's disease, there are cases of significant cognitive impairment in two women associated with statin use, highlighting the need for clinicians to monitor cognitive function in patients on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive impairment associated with atorvastatin and simvastatin. King, DS., Wilburn, AJ., Wofford, MR., et al.[2022]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5412714/

The effect of statins on rate of cognitive decline in mild ... All cognitive assessments trended toward less decline when subjects were concurrently treated with a statin, supporting the position that statins do not have a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11550230/

Do Statins Affect Cognitive Health? A Narrative Review and ... A duration–response relationship has been observed with one study finding a 9% reduction in dementia with each year of statin treatment [38].

3. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1526959/full

Correlation of atorvastatin with subjective memory deficits Some studies have linked long-term or high-dose use to cognitive decline, including memory loss and poor concentration (21–24). Although usually ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70039

Statin use and dementia risk: A systematic review and ... Atorvastatin reduced dementia risk by approximately 11% in a subgroup with eight studies, and fluvastatin by 7%, in an analysis with seven ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/62/supplement_1/102

Lipophilic Statins in Subjects with Early Mild Cognitive ... Lipophilic statin use was associated with more than double the risk of converting to dementia over eight years of follow-up compared with statin non-use.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5830056/

The role of statins in both cognitive impairment and protection ... Statins have also been shown to decrease the risk of dementia, Alzheimer's disease, and improve cognitive impairment in some cases.

7. jacc.org jacc.org/doi/10.1016/j.jacc.2021.04.075

Statin Therapy on Cognitive Decline and Incident Dementia In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0019483221004570?via%3Dihub

Is the use of high-intensity atorvastatin associated with ... There was a small improvement in immediate recall (baseline score 8.5 ± 2.5, 6 months 9.04 ± 1.8; p = 0.05), and delayed recall (baseline 6.1 ± 2.6, 6 months ...