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

Higher levels of HDL-C-;known as the "good cholesterol"-;have been shown to correlate with heightened risk for Alzheimer's disease. A new study published in the Journal of Clinical Endocrinology & Metabolism might explain why. Once women reach the menopause transition, it's a matter of the quality, rather than quantity, of the total cholesterol carried by HDL particles circulating in a woman's bloodstream, and that quality declines over time, according to a research team led by a University of Pittsburgh School of Public Health epidemiologist.

HDL particles vary in their size, composition and level of functioning. The team measured these features in the blood of 503 women from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study. The researchers found that, over time, the number of larger HDL particles in the women's bodies increased-;and these larger particles, unfortunately, did not function as well as their smaller counterparts. 

The researchers conducted repeated assessments of study participants' cognitive function from 2000 to 2016 and compared these data to changes in the women's HDL particles, composition and function as they aged.

"We were able to show that as early as midlife, women who have more of the smaller-sized particles and those whose particles' concentrations of phospholipids increased over the menopause transition are more likely to experience better episodic memory later in life," said Samar R. El Khoudary, Ph.D., M.P.H., professor of epidemiology at Pitt Public Health, adding that loss of working memory is the first sign of Alzheimer's disease.

Previously, El Khoudary's team has shown that health behaviors-;such as those included in the American Heart Association's (AHA) Life's Essential 8-;work to improve the quality of HDL particles, for example by adding more of the phospholipid-rich particles in the bloodstream.

That's the good news in this developing picture of brain health and the 'not-so-good-after-all' cholesterol. Even though higher levels of HDL-C may not be protective as you get older, there are things you can do that might help, even as early as your 40s. The same, modifiable risk factors that the AHA is advocating for-;including physical activity, ideal body weight and quitting smoking-;can help you protect your brain, too." 

Samar R. El Khoudary, Ph.D., M.P.H., professor of epidemiology, Pitt Public Health

Meiyuzhen Qi, Ph.D., post-doctoral researcher in the Department of Epidemiology at Pitt Public Health, is first author of this study. Additional coauthors include scientists 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.