Research uncovers new links between blood lipid profiles and risk of developing Alzheimer's

People who are at higher risk for heart disease also seem more likely to develop dementia.

And research led by The University of Texas Health Science Center at San Antonio (UT Health San Antonio) has discovered new associations between various lipid, or fat, levels in the blood and the risk of developing Alzheimer's disease, the most common cause of dementia worldwide.

The findings mean that using blood lipid profiles could help better understand, predict and possibly even prevent the disease in the future.

In more than 800 older adults who were part of the long-running Framingham Heart Study, the researchers found that higher levels of small dense cholesterol particles – which are known to increase the risk of atherosclerosis and coronary heart disease – were associated with higher risk of developing Alzheimer's disease.

However, higher levels of a marker for small fat-carrying particles, which are involved in the transport of dietary fats from the gut to other body tissues through the blood after eating, were associated with lower risk of developing the disease.

Perhaps ironically, the researchers also discovered that individuals who had the lowest levels of highly dense cholesterol particles – often referred to as "good cholesterol" as it is considered protective against cardiovascular disease – had a lower risk of developing Alzheimer's disease compared to the rest of the included individuals.

These findings highlight the complex relationships of blood lipids with both heart and brain health, suggesting the possibility of certain blood lipids playing different roles in cardiovascular disease and dementia-related biological processes."

Sokratis Charisis, MD, researcher with the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio

Charisis is first author of the study published May 30 in the journal Neurology, titled, "Association of Blood Lipoprotein Levels With Incident Alzheimer's Disease in Community-Dwelling Individuals: The Framingham Heart Study." Other authors include corresponding author Sudha Seshadri, MD, director of the Biggs Institute, and researchers from Boston University School of Public Health, the University of Texas Rio Grande Valley and the Framingham Heart Study.

A community-based analysis

The new study notes that dementia is a leading source of morbidity and mortality in the aging population. Worldwide, there were 57.4 million people living with dementia in 2019, a number that is expected to reach 152.8 million by 2050.

However, there is a general trend over time of decreasing incidence of Alzheimer's disease and other dementias in the U.S. and other higher-income countries that is at least partially attributed to better management of cardiovascular risk factors.

The Framingham Heart Study is an ongoing, community-based cohort study that was launched in 1948 in Framingham, Massachusetts. Residents there ages 30 to 59 were randomly selected from census data to participate. Those with definite signs of cardiovascular disease at baseline were excluded. Participants of the original cohort have undergone up to 32 examinations performed every two years, which have included detailed history-taking by a physician, a physical examination and lab testing.

The latest analysis by researchers led by UT Health San Antonio included participants from the original cohort who were 60 years or older and free of dementia during an examination period of 1985-1988, and had available cognitive follow-up and lipoprotein marker data. Lipoproteins act as a transport system for lipids in the bloodstream.

Blood lipid levels and dementia

Levels of high-density lipoprotein cholesterol (HDL-C), or good cholesterol; low-density lipoprotein cholesterol (LDL-C), or "bad cholesterol"; small dense LDL-C (sdLDL-C); and other lipoprotein types associated with heart disease were measured in blood samples obtained from the mid- to late-'80s examination period. The Framingham participants were watched for incident Alzheimer's disease, meaning a first diagnosis of the disease, until 2020.

Of a total of 822 participants, 128 developed incident Alzheimer's disease.

The researchers discovered that an increase of 1 standard deviation unit (SDU) of a concentration of small dense LDL-C (sdLDL-C), a value representing how far a specific data point deviates from the mean, was associated with a 21% increase in the risk for incident Alzheimer's disease.

As the name implies, small dense LDL-C (sdLDL-C) is a type of the so-called bad cholesterol with smaller and denser particles than other low-density lipoproteins, and that is considered more likely to form plaque in arteries, strongly associated with an increased risk of atherosclerotic cardiovascular disease.

A 1 SDU increase in a concentration of ApoB48, a lipoprotein that transports dietary fat from the intestines and into the bloodstream that also is tied to heart disease and cardiovascular problems, was found to be associated with a 22% decrease in the risk for incident Alzheimer's disease.

Participants in the first quartile of HDL-C, or good cholesterol – in order of lesser amounts – were 44% less likely to develop Alzheimer's compared with those in the second, third and fourth quartiles. And those with small dense LDL-C concentrations below the median were 38% less likely to develop Alzheimer's compared with those with concentrations above the median.

In summary, then, lower small-density bad cholesterol (sdLDL-C) concentrations and higher ApoB48 concentrations were associated with a lower Alzheimer's risk. And individuals with the lowest good cholesterol (HDL-C) concentrations were less likely to develop Alzheimer's compared with the remaining sample.

"These findings underscore links between lipoprotein metabolism pathways and Alzheimer's risk, emphasizing the potential role of blood lipoprotein markers in Alzheimer's risk stratification and of lipid modification strategies in dementia prevention," the researchers concluded.