How Cholesterol and Triglyceride Levels are Related to Alzheimer’s Disease

Higher levels of HDL-C, also known as “good cholesterol,” have been shown to correlate with an increased risk of Alzheimer’s disease. A new study published in the Journal of Clinical Endocrinology & Metabolism may explain why. Once women reach menopause, it is more a question of the quality than the quantity of total cholesterol carried by HDL particles in a woman’s bloodstream, and that quality declines over time, according to a team of researchers led by an epidemiologist from the University of Pittsburgh School of Public Health.

HDL-C Levels and Alzheimer’s

The team measured these characteristics in the blood of 503 women from the HDL sub-study of the Study of Women’s Health Across the Nation (SWAN). The researchers found that the number of larger HDL particles in the women’s bodies increased over time – and unfortunately, these larger particles did not work as well as their smaller counterparts.

The researchers conducted repeated assessments of the cognitive function of the study participants from 2000 to 2016 and compared this data with changes in HDL particles, composition and function in women as they aged. “We were able to show that women who have more of the smaller particles at midlife and whose particle concentrations of phospholipids increase during menopause are more likely to have 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 working memory loss 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 Essential 8” – improve the quality of HDL particles, for example by increasing the number of phospholipid-rich particles in the bloodstream. “While higher HDL-C levels may no longer be protective as we age, there are steps we can take starting in our 40s that can help, according to the researchers. The same modifiable risk factors the AHA advocates – including physical activity, ideal body weight and smoking cessation – can also help protect the brain.”

Lower HDL and High Triglyceride Levels at Age 35 and Alzheimer’s

But even a relatively young age can increase your risk of dementia, according to research. Living your best life at 35 while ignoring cholesterol and glucose levels can increase your chances of developing Alzheimer’s later in life. According to scientists at the Boston University School of Medicine (BUSM), lower high-density lipoprotein cholesterol (HDL) and high triglyceride levels measured in the blood at the age of 35 are associated with a higher incidence of Alzheimer’s disease several decades later in life. They also found that high blood sugar levels measured between the ages of 51 and 60 are associated with future risk of Alzheimer’s.

“While our findings confirm other studies that established a link between blood cholesterol and glucose levels and future risk of Alzheimer’s disease, we have shown for the first time that these links occur much earlier in life than previously thought,” explains senior author Lindsay A. Farrer, PhD, chief of biomedical genetics at BUSM. The researchers believe that while high LDL levels have consistently been linked to AD risk in many previous studies, the association between HDL and AD has been inconclusive, possibly because most studies examining these associations have been conducted in individuals who were 55 years of age or older at baseline.

This study was conducted using data obtained from participants in the Framingham Heart Study who were examined at approximately four-year intervals for most of their adult lives. The correlations of Alzheimer’s with several known risk factors for cardiovascular disease and diabetes (including HDL, LDL, triglycerides, glucose, blood pressure, smoking and body mass index) were measured at each examination and in three age periods during adulthood (35-50, 51-60, 61-70). The researchers found that low HDL (the good cholesterol) was indicative of Alzheimer’s disease in early (35-50 years) and mid (51-60 years) adulthood, and that high blood sugar (a precursor to diabetes) in mid-adulthood was also indicative of Alzheimer’s disease. These findings demonstrate for the first time that cardiovascular risk factors, including HDL, which has not been consistently recognized as a strong risk factor for Alzheimer’s, contribute to future Alzheimer’s risk beginning as early as age 35,” said first and corresponding author Xiaoling Zhang, MD, PhD, an assistant professor of medicine at BUSM.

Careful Control is Crucial

According to the researchers, careful control of these factors from early adulthood onward can reduce the risk of cardiovascular disease, diabetes and Alzheimer’s disease. An intervention aimed at controlling cholesterol and glucose from early adulthood onward can help maximize cognitive health in later life.

Farrer also points out that the unique design and mission of the Framingham Heart Study, a community-based prospective multi-generation health study that began in 1948, allowed them to link Alzheimer’s to risk factors for heart disease and diabetes measured much earlier in life than is possible in most other studies of cognitive decline and dementia. These findings have been published online in Alzheimers & Dementia: The Journal of the Alzheimer’s Association.