HDL Cholesterol Linked to Greater Gray Matter Volume in the Brain

High-density lipoprotein (HDL), or “good” cholesterol, may play a vital role in conserving healthy brain matter in middle-aged adults, according to a report from UT Southwestern Medical Center researchers. The findings, published in the Journal of Clinical Medicine, could give doctors and patients more insight into factors that affect cognitive health in aging adults.

“Our study has identified a novel role of HDL cholesterol function in maintaining gray matter volume in the brain, which is important for cognitive function in middle-aged adults,” said the study’s first author, John Giacona, PhD, PA-C, Assistant Professor of Applied Clinical Research and Internal Medicine in the School of Health Professions at UT Southwestern. “Our study was the first to investigate for a potential link between HDL function and brain volume.”

To determine whether there was a link, the researchers assessed 1,826 participants between the ages of 35 and 70 enrolled in the multiethnic, population-based Dallas Heart Study, a longitudinal study now in its 25th year.

First, fasting lipoprotein concentrations were assessed using nuclear magnetic resonance. Participants were then tested for cognitive function, and their brain matter volume was measured using brain MRI. Initial assessments took place between 2000 and 2002, and participants were reassessed between 2007 and 2009.

Anand Rohatgi, MD, Professor of Internal Medicine in the Division of Cardiology, and his team at UTSW’s Clinical Heart and Vascular Center measured HDL function in this study. Their findings revealed that higher concentrations of small-particle HDL, but not larger particles or total HDL concentration, were linked with greater gray matter volume and higher cognitive capacity.

“Previous research has shown conflicting evidence regarding the concentration of HDL cholesterol in development of dementia or brain atrophy,” said senior author Wanpen Vongpatanasin, MD, Professor of Internal Medicine and Director of the Hypertension Section in the Division of Cardiology at UTSW. “However, the concentration of HDL cholesterol may not reflect their function.”

HDL decreases the amount of low-density lipoprotein (LDL), or “bad” cholesterol, in blood vessels by transporting the excess to the liver, where it gets broken down. “In addition, HDL particles exist in many sizes, which may be linked to their function,” Dr Vongpatanasin said. “We now need to understand exactly how the small HDL particle, which can cross the blood-brain barrier, may have a beneficial role in maintaining brain health.”

This finding led the researchers to note that HDL cholesterol function or levels of small HDL particles may be used as markers for a population at risk of developing cognitive decline, though additional studies would be required to confirm the connection.

Drs Giacona and Vongpatanasin credit UTSW’s multidisciplinary collaboration for the study’s success.

“Our unified focus on heart and brain health fosters multidisciplinary collaboration among the Cardiology, Neurology, and Advanced Imaging Research Center departments,” said Dr Giacona, who is also a certified Hypertension Specialist at the Clinical Heart and Vascular Center as a member of the Hypertension Section. He said this research “has extended the potential beneficial role of HDL cholesterol efflux function to the brain.”

Cholesterol efflux is the ability of HDL to “scoop up” cholesterol particles from plaques in the heart’s blood vessels and move those particles to the liver for disposal.