Cholesterol and Dementia: Can Treating One Prevent the Other?

For some time, the clinical community has been talking about the potential relationship between high total cholesterol in mid-life impacting a patient’s risk for dementia later on. While the number of studies on the subject has been sparse, a recent review of all available medical literature is beginning to clarify the picture.

One study demonstrated that a high cholesterol diet leads to memory deficits, increases oxidative stress and doubles the concentration of amyloid-β in the hippocampus. Another study established a link between cholesterol and Alzheimer’s disease (AD) supported by the identification of clusters of genes (apolipoprotein E4, single-nucleotide polymorphisms for clusterin (CLU), ABCA7, and PICALM) that influence lipid binding and metabolism in the brain. And yet another study specifically looks at mid-life high total serum cholesterol and links it to sporadic Alzheimer’s disease.

Researchers speculate that the impact of total cholesterol on arteriosclerosis or cerebrovascular disease may also impact the risk for Alzheimer’s Disease, in addition to presenting a direct risk factor for Alzheimer’s. The overall conclusion is that high total cholesterol in a patient’s mid-life stage (>6.5 mmol/l) may increase Alzheimer’s disease risk and that cholesterol maintenance in the normal range, through lifestyle changes such as diet and exercise, during this phase of life is recommended.

But further evaluation is needed to accurate clarify the relationship between total cholesterol and Alzheimer’s. The challenge to providing an accurate assessment is the fact that patients would need to be followed for decades after an intervention to lower cholesterol levels, and would it be unethical to have a control group go untreated for this period of time.

Cholesterol as a Cause of Dementia and the Effect of Medication

There is currently not enough evidence to suggest a relationship between mid-life high cholesterol levels and other types of dementia. There is also not enough data to show whether medication such as statins can reduce the risk of Alzheimer’s disease or research to support a positive impact on other forms of dementia. It’s hoped that more epidemiological data will become available as information is collected on the use of statins in the future.

High Cholesterol in Late-life and Alzheimer’s Disease

In late-life, total cholesterol is not currently associated with dementia. But the authors of this review are hesitant to conclude that there is no biological association between late-life lipids and brain health, as there were a small number of studies to review and they feel that more evaluation is needed. They added that total cholesterol levels can vary due to variables including genetics, diet, region, rural versus urban living, ethnicity and income. Much more research is needed to full comprehend the impact of these factors not only on cholesterol, but how both separately and together they might alter the risk profile for Alzheimer’s disease and other dementias. We’re starting to get a better idea of the need for cholesterol maintenance to reduce the possibility of its role as a cause of dementia and to reduce the threat of Alzheimer’s in particular. But we’ve only scratched the surface in developing a clear profile that can help a patient assess their level of risk and take steps to mitigate the possibility of developing one of these highly debilitating diseases in the future.