Reevaluating Statins: Cardiovascular Protection and Cognitive Health

Since the introduction of Lovastatin in 1987, statins have been central to cholesterol management and cardiovascular disease prevention. I was an early adopter, optimistic that lowering cholesterol would reduce heart attacks and other cardiovascular events. With the release of the second statin, Pravastatin, in 1991, new research highlighted that inflammation—not just cholesterol—was a key driver of vascular disease.

This shift led to statins being marketed as both cholesterol-lowering and anti-inflammatory drugs, addressing multiple aspects of coronary artery disease (Circulation Research, 2002). As evidence evolved, so did the understanding of inflammation's role in many chronic diseases.

Conditions such as diabetes, hypertension, and metabolic syndrome contribute to systemic inflammation that affects all organs, particularly the heart and brain. Over time, I began to see that an anti-inflammatory approach—one focused on reducing underlying metabolic and inflammatory drivers—might be a more sustainable path for long-term cardiovascular health.

Given the various side effects associated with statins, including their potential impacts on brain health, less toxic anti-inflammatory therapies may offer a safer option for managing cardiovascular risk in certain populations.

Cholesterol’s Role in the Brain: From Newborn to Aging Adult

In newborns and toddlers, cholesterol levels are naturally low, typically ranging from 70 to 100 mg/dL—much lower than typical adult levels. Despite this, the brain undergoes rapid growth and development during this period.

Why? Because the brain makes its own cholesterol.

Unlike other organs, the brain is isolated by the blood-brain barrier, preventing cholesterol from crossing in either direction. This means that the brain relies entirely on local cholesterol production—primarily by astrocytes, which synthesize cholesterol to support neuronal growth, myelin formation, and synaptic function. The brain contains about 25% of the total cholesterol in our body even though it constitutes only 2% of our body weight. Cholesterol is essential for neuron structure, synapse formation, transmitter function and the production of the insulating fibers known as myelin. Disruption of the production and metabolism of brain cholesterol may increase Alzheimer’s risk due to impairment of any of the processes that have been explained above.

Aging, Cholesterol, and Cognitive Health

As we age, the capacity for cholesterol synthesis in the brain declines (Neurobiology of Aging, 2015). At the same time, conditions such as diabetes, hypertension, and metabolic syndrome—common in older adults—can impair cholesterol metabolism, potentially affecting cognitive resilience.

• Low cholesterol levels in older adults have been linked to cognitive impairment. A JAMA Neurology (2018) study found that total cholesterol levels below 160 mg/dL were associated with an increased risk of dementia.

• Cholesterol plays a crucial role in synaptic plasticity and neurotransmission. Reduced brain cholesterol levels may impair memory, learning, and neuronal repair mechanisms (Progress in Lipid Research, 2020).

• The brain uses cholesterol to produce neurosteroids, such as pregnenolone and allopregnanolone, which support cognitive function and stress resilience (Frontiers in Aging Neuroscience, 2016).

Could Aggressive Cholesterol Lowering Increase the Risk of Neurodegenerative Diseases?

Alzheimer’s disease, the most common neurodegenerative disorder, is now recognized as an inflammatory process that also disrupts cholesterol synthesis in the brain. This dysfunction leads to reduced neuronal function and impaired synaptic connections, both of which are crucial for cognition.

The initial inflammatory response disrupts the blood-brain barrier, allowing toxins and oxidized LDL particles to penetrate brain tissue and impair cellular function. This inflammation increases the production and reduces the clearance of beta-amyloid and tau proteins, the hallmarks of Alzheimer’s disease. Over time, these disruptions contribute to mitochondrial dysfunction, reduced cholesterol synthesis, and cognitive decline.

Additionally, insulin resistance—a consequence of chronic inflammation—further exacerbates neurodegeneration. Insulin resistance has been strongly linked to an increased risk of Alzheimer’s disease, leading some researchers to refer to the condition as "Type 3 Diabetes" (Journal of Diabetes Research, 2020). When neurons become insulin resistant, their ability to absorb glucose for energy is impaired, leading to cellular energy deficits that accelerate neuronal decline. Excess insulin levels also interfere with beta-amyloid clearance, compounding the accumulation of harmful plaques. This dual impact of energy starvation and increased plaque formation creates a powerful driver of neurodegeneration.

Since statins have been associated with an increased risk of insulin resistance and new-onset diabetes, particularly at higher doses (JAMA Internal Medicine, 2022), it is worth questioning whether they may unintentionally contribute to the very metabolic dysfunction that accelerates cognitive decline.

This cascade of inflammation, metabolic dysfunction, and impaired cholesterol metabolism ultimately results in the irreversible degeneration of brain tissue.

Statins, Cholesterol, and the Blood-Brain Barrier

Statins are classified into two main categories based on their solubility and ability to penetrate the blood-brain barrier:

Lipophilic statins (Atorvastatin, Simvastatin, Fluvastatin, Lovastatin, Pitavastatin)

• Fat-soluble, allowing them to cross cell membranes, including the blood-brain barrier more readily.

• More likely to interfere with brain cholesterol synthesis and impact cognitive function.

Hydrophilic statins (Pravastatin, Rosuvastatin)

• Water-soluble, with a stronger preference for liver cells.

• Less likely to cross the blood-brain barrier, though they can still affect brain cholesterol metabolism under conditions of increased blood-brain barrier permeability (such as in inflammation or metabolic disease).

Since cholesterol is essential for neuron function and neurotransmission, any significant disruption in cholesterol synthesis could theoretically impair synaptic communication and neuronal repair mechanisms. Some clinical evidence suggests that lipophilic statins may interfere with brain cholesterol production, potentially contributing to neurodegeneration and cognitive decline.

The FDA has acknowledged that cognitive impairment is a potential risk of statin therapy, particularly in patients with pre-existing cognitive issues.

Do Statins Reduce Alzheimer’s Risk?

Currently, there is no clear evidence that statins prevent Alzheimer’s disease. Some short-term studies (3-5 years) have suggested a modest reduction in dementia risk, but these findings must be interpreted with caution.

Alzheimer’s disease develops over decades, long before symptoms appear.

Short-term drug trials may not capture long-term risks, making it difficult to draw definitive conclusions about statins' impact on dementia risk.

Given these uncertainties, I believe a cautious approach is warranted, particularly for patients with mild cognitive impairment (MCI) or early signs of Alzheimer’s disease. The potential risks of statins on cognitive function must be weighed against their modest cardiovascular benefits.

In cases where metabolic dysfunction or inflammation compromises the blood-brain barrier, lipophilic statins may more easily enter brain tissue, increasing the potential for adverse effects on cognition.

Considering that statins have shown only minimal absolute risk reduction in primary prevention; it is reasonable to question whether their use or continuation is justified in older individuals who may already be vulnerable to cognitive decline. For these patients, the potential harm to brain health may outweigh the small benefit in cardiovascular risk reduction.

The Role of CoQ10: Mitochondrial Health, Brain Function, and Statins

One critical but often overlooked factor in statin therapy is the depletion of coenzyme Q10 (CoQ10), an essential component of mitochondrial energy production.

Why is CoQ10 Important?

• CoQ10 is essential for ATP production – The brain is the most energy-demanding organ in the body, and neurons rely on mitochondrial function to maintain synaptic activity and cognitive processes (Neurobiology of Aging, 2018).

• CoQ10 protects against oxidative stress – It neutralizes free radicals, reducing neuroinflammation and aging-related damage (Frontiers in Neuroscience, 2020).

• It supports neurotransmitter balance – CoQ10 helps regulate dopamine, serotonin, and acetylcholine, which are crucial for mood, memory, and executive function (Molecular Neurobiology, 2021).

CoQ10, Aging, and Neurodegeneration

 • CoQ10 levels naturally decline with age – This reduction has been implicated in age-related cognitive decline and neurodegenerative diseases (Brain Research, 2017).

• Low CoQ10 levels have been linked to Parkinson’s and Alzheimer’s disease – Some studies suggest that CoQ10 supplementation may slow neurodegeneration in these conditions (Annals of Neurology, 2019).

Statins and CoQ10 Depletion: A Hidden Risk for Cognitive Decline?

Statins block the same pathway (the mevalonate pathway) that produces cholesterol and CoQ10. As a result, statin users may experience a progressive decline in CoQ10 levels, which could worsen mitochondrial dysfunction and contribute to cognitive issues.

For individuals experiencing memory loss, brain fog, or fatigue while on statins, CoQ10 supplementation may help restore mitochondrial function and potentially improve cognitive function.

Prioritizing Brain Health Holistically

For those concerned with cognitive health, lifestyle interventions often provide superior long-term support to both brain and heart health.

Key Strategies:

· Regular Exercise – Aerobic and resistance training enhance brain-derived neurotrophic factor (BDNF), supporting neuroplasticity and cognitive function.

· Anti-Inflammatory Diet – A Mediterranean diet rich in omega-3s, polyphenols, and antioxidants reduces neuroinflammation and supports brain health.

· Vitamin D, Fish Oil, & CoQ10 – Vitamin D supports cognitive resilience, high-dose DHA (from fish oil) protects neuronal function, and CoQ10 supplementation may restore mitochondrial energy production in statin users.

· B Vitamins & Ashwagandha – B vitamins support homocysteine regulation, reducing brain atrophy rates, while Ashwagandha has neuroprotective and anti-anxiety properties (Frontiers in Aging Neuroscience, 2019).

· Reducing Alcohol & Managing Stress – Both chronic stress and excessive alcohol consumption accelerate brain aging and neurodegeneration.

· Prioritizing Sleep – Sleep is essential for amyloid-beta clearance, reducing the risk of Alzheimer’s disease.

Final Thoughts

Statins are not inherently “bad” drugs—but like any medication, they should be used selectively, with a clear understanding of their benefits and risks.

• For those with a history of heart disease, statins may provide some degree of cardiovascular protection.

• For low-risk individuals, particularly those concerned about cognitive health, statin therapy should be carefully reconsidered.

Additionally, given that statins lower CoQ10 levels, supplementation may offer neuroprotective benefits—particularly for older adults at risk for cognitive decline, mitochondrial dysfunction, or neurodegenerative disease.

The best approach to longevity is not just about lowering cholesterol—it’s about reducing chronic inflammation, maintaining metabolic health, and protecting the brain’s ability to function optimally for decades to come.

In the end, if the absolute cardiovascular benefit of statins is so small in primary prevention, is it worth the trade-off of potentially undermining the brain—the organ that shapes who we are, how we experience life, and how we connect with those we love and share in the moments that matter most?