Study reveals how cholesterol can contribute to Alzheimer’s risk

Experts recognize the link between high cholesterol and Alzheimer’s disease and vascular dementia. However, the reasons behind this association are uncertain.

A study from the National Institute on Aging has investigated the underlying causes for this connection.

According to the Mayo Clinic, high cholesterol is among the vascular dementia risk factors. Vascular dementia is a general term for brain damage from impaired blood flow that causes issues with reasoning, planning, judgment, memory and other thought processes. This type of dementia is rare before age 65.

Meanwhile, a 2019 study has linked early-onset Alzheimer’s disease, which occurs before 65, to high LDL cholesterol. LDL cholesterol is considered “bad.”

In the new NIA study, research led by staff scientist Vijay Varma suggests that interruptions in the conversion of cholesterol to bile acids may contribute to dementia development.

Researchers investigated this link by recruiting over 1,800 participants from the Baltimore Longitudinal Study of Aging (BLSA) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Initially, the team examined whether the cholesterol breakdown was linked to brain anomalies characteristic of vascular dementia and Alzheimer’s disease. Afterward, they focused on a test involving bile acid sequestrants. This medication helps decrease LDL cholesterol by limiting how much is absorbed into the bloodstream. The team investigated if bile acid sequestrants were connected to an increased risk of dementia. They examined over 26,000 patients in U.K. general practice clinics to make that determination. Then, they reviewed 29 autopsy samples from the BLSA. This determined if Alzheimer’s disease patients’ brains tend to have altered bile acid levels.

Results showed that vascular dementia didn’t increase for females, but it did for males. Males had higher prescriptions of bile acid-blocking medications. This indicates cholesterol breakdown and bile acid synthesis may affect dementia progression. It’s thought that this occurs through brain signaling pathways specifically affected by being male or female.

Researchers say more studies are needed, however.

“To further extend these findings, we are now testing whether approved drugs for other diseases that may correct bile acid signaling abnormalities in the brain could be novel treatments for Alzheimer’s disease and related dementias,” senior author Dr. Madhav Thambisetty, Ph.D., investigator and chief of the Unit of Clinical and Translational Neuroscience in the NIA’s Laboratory of Behavioral Neuroscience said in a statement. “These analyses are being pursued in the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study.”

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