The effect of cholesterol on the brain is complex. High cholesterol has been linked to Alzheimer's disease and a greater risk for certain strokes. Low cholesterol, however, may have some negative effects on the brain. [See Box Consequences of Low Cholesterol Levels.]

High Cholesterol and Ischemic Stroke

Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, which is a type of stroke caused by blockage of the carotid arteries, those carrying blood to the brain. The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dl.

HDL may even reduce the risk for hemorrhagic stroke, which is a less common stroke caused by bleeding in the brain and associated with low overall cholesterol levels. [See Box Consequences of Low Cholesterol Levels.]

High Cholesterol and Late-Onset Alzheimer's Disease (AD)

There has been research suggesting an association between high cholesterol levels and Alzheimer's disease (AD) in some people. The major target in genetic research on late-onset AD has been apolipoprotein E (ApoE), which plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury. People who carry a variant of this gene (ApoE4) are at significantly higher risk for AD. (Other variants may even reduce the risk.) High cholesterol may pose a risk for Alzheimer's regardless of this genetic factor, however. A number of recent studies support the link between Alzheimer's disease and cholesterol by suggesting that certain cholesterol-lowing drugs statin drugs known as statins may be protective against AD. (Of interest are studies reporting that cholesterol is important within the brain for cell communication and memory, but such benefits do not apply to high cholesterol levels in the blood.)

Consequences of Low Cholesterol Levels

The negative consequences of low cholesterol levels, whether actively lowered or naturally low, are the subject of ongoing debate. In one study, men with the lowest cholesterol levels had the highest mortality rate, generally due to cancer and other, non-heart related diseases. An analysis of this study along with additional research suggests strongly, however, that this higher death rate is almost totally due to lung cancer in smokers with low cholesterol.

Cognitive Function and Depression

Effects of Natural Low Cholesterol Levels. Some studies have found that cholesterol is important for the production of serotonin, a chemical in the brain that at low levels is associated with depression. Men with naturally low cholesterol levels also have low serotonin levels.

Some evidence has reported a link between natural low natural cholesterol levels and negative emotional states:
  • One study found that male psychiatric patients with cholesterol below 160 mg/dl had twice the normal rate of suicide and that elderly men with low cholesterol levels had three times the normal risk of depression.

  • Another 2000 study supported earlier work on an association between depression and chronically low cholesterol levels.

  • In a large 2001 Swedish study, violent behavior was linked with naturally low cholesterol levels.

  • A 2000 study of patients with depression and bipolar disorders found lower cholesterol levels during specific manic or depressive episodes. The study suggested that mood states might produce low cholesterol levels, not vice versa.
Some researchers have observed that people with low cholesterol levels due to medical conditions or alcoholism are often also deficient in dietary fats known as omega-3 fatty acids. Low levels of omega-3s, which are found in oily fish, are linked with depression and aggression. In fact, some studies in which cholesterol was lowered using diets that included omega-3 fatty acids reported less depression. Clearly, any link between low cholesterol levels and emotional disorders is uncertain.

Effects of Medication-Induced Low Cholesterol Levels. Importantly, numerous studies have reported no association between the use of cholesterol-lowering drugs and depression or rates of suicide, accidents, or violent death.

Hemorrhagic Stroke

People with overall cholesterol levels below 180 mg/dl may be at risk for hemorrhagic stroke (which is bleeding in the brain), particularly if they also have high blood pressure. It should be noted, however, that this type of stroke is much less common than ischemic stroke (which is caused by artery blockage and may be related to low HDL cholesterol).

Definition of Cholesterol, Other Lipids, and Lipoproteins, Effects of Cholesterol and Lipids on the Heart, Effects of Cholesterol and Lipids on the Brain, Risk Factors for Unhealthy Lipid Levels, Symptoms of Unhealthy Levels of Cholesterol, Diagnosis and Screening, Lifestyle Modifications, Drug Treatments, Support Organizations

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