Cholesterol-lowering drugs may protect against Alzheimer's and age-related dementia

A comprehensive meta-analysis involving approximately one million participants has revealed that lowering cholesterol levels not only benefits the heart but may also reduce the risk of Alzheimer’s disease and age-related dementia, according to researchers from the University of Bristol in the United Kingdom and the University of Copenhagen Hospital in Denmark.

The research team explained that common cholesterol-lowering medications, including statins and ezetimibe, may offer additional cognitive health benefits. This study builds on previous research linking low-density lipoprotein (LDL) cholesterol to dementia.

Rather than tracking individuals already taking cholesterol-lowering drugs, the researchers relied on genetic variants that naturally lower cholesterol as a substitute for lifelong statin use. This methodology, known as Mendelian randomization, spares researchers from the need to meticulously monitor confounding factors such as diet and physical activity.

The analysis results highlighted several notable indicators regarding the relationship between cholesterol reduction and dementia risk:

• The association persisted even after accounting for the APOE ε4 gene, the strongest known genetic risk factor for Alzheimer’s disease.

• The researchers found no clear evidence of a similar effect for other genes, such as PCSK9, ANGPTL4, and LPL, although they did not rule out the possibility of future impacts.

Leiv Tebar Nordstrøm, a clinical biochemist who worked at the University of Bristol during the study, noted that possessing these cholesterol-lowering genetic variants appears to be associated with a significant reduction in the risk of developing dementia.

The researchers suggest that atherosclerosis, resulting from the accumulation of cholesterol-rich fatty deposits in blood vessels, represents a fundamental feature of this relationship. This condition can lead to brain damage due to impaired blood flow, a factor known to be a primary driver of certain types of dementia.

The research team hopes to conduct randomized clinical trials lasting between 10 and 30 years, in which cholesterol-lowering drugs are administered to a group of participants, and their direct impact on subsequent dementia risk is monitored. Such studies would definitively confirm the link revealed by the current research.

The study, published in the journal Alzheimer's & Dementia, indicated that lowering cholesterol at an early age is likely to reduce the risk of developing dementia later in life, at a time when approximately 57 million people worldwide are living with the disease.