Understanding the surprising link between HDL cholesterol quality and Alzheimer’s disease risk

Higher levels of HDL-C, called “good cholesterol,” have been shown to correlate with an increased risk of Alzheimer’s disease. A up-to-date study published in the journal Journal of Clinical Endocrinology & Metabolism can explain why. According to a research team led by the University of Pittsburgh, when a woman enters menopause, it is about the quality, rather than the quantity, of total cholesterol carried by the HDL particles circulating in her bloodstream, and this quality declines over time. Epidemiologist at the School of Public Health.

HDL particles vary in size, composition and level of functioning. The team measured these characteristics in the blood of 503 women participating in the HDL Supplementary Study of Women’s Health Across the Nation (SWAN). Scientists found that over time, the number of larger HDL particles in women’s bodies increased, and these larger particles unfortunately did not work as well as their smaller counterparts.

The researchers conducted repeated assessments of study participants’ cognitive function between 2000 and 2016 and compared this data with changes in HDL particles, composition and functioning as women aged.

“We were able to show that, already in midlife, women who have more smaller particle sizes and those whose phospholipid particle concentrations increased during menopause are more likely to have better episodic memory later in life,” Samar said. R. El Khoudary, Ph.D., MPH, professor of epidemiology at Pitt Public Health, added that loss of working memory is the first sign of Alzheimer’s disease.

Previously, El Khoudary’s team showed that health behaviors – such as those included in the American Heart Association’s (AHA) Life’s Necessary 8 list – improve the quality of HDL particles, for example by adding more phospholipid-rich particles to the bloodstream.

That’s good news in this evolving picture of brain health and “not-so-good” cholesterol. Although higher levels of HDL-C may not provide protection as you age, there are things you can do that may support even after the age of 40. The same modifiable risk factors that the AHA advocates, including physical activity, ideal body weight and quitting smoking, may also support protect the brain.

Samar R. El Khoudary, Ph.D., MPH, professor of epidemiology, Pitt Public Health

The first author of this study is Dr. Meiyuzhen Qi, a postdoctoral researcher in the Department of Epidemiology at Pitt Public Health. Additional co-authors include researchers from the University of Pennsylvania Perelman School of Medicine, Rush University Rush Medical Center, University of California Los Angeles David Geffen School of Medicine, Albert Einstein College of Medicine, University of Michigan School of Public Health, and University of Massachusetts Medical School.