University of California San Francisco Study Finds Both High and Low Levels of High-Density Lipoprotein Cholesterol Associated with Increased Dementia Risk
If validated, study findings may result in new biomarkers for clinical laboratory cholesterol tests and for diagnosing dementia
Researchers continue to find new associations between biomarkers commonly tested by clinical laboratories and certain health conditions and diseases. One recent example comes from research conducted by the University of California San Francisco. The UCSF study connected cholesterol biomarkers generally used for managing cardiovascular disease with an increased risk for dementia as well.
The researchers found that both high and low levels of high-density lipoprotein (HDL)—often referred to as “good” cholesterol—was associated with dementia in older adults, according to a news release from the American Academy of Neurology (AAN).
UCSF’s large, longitudinal study incorporated data from 184,367 people in the Kaiser Permanente Northern California health plan. How the findings may alter cholesterol biomarker use in future diagnostics has not been determined.
The researchers published their findings in the journal Neurology titled, “Low- and High-Density Lipoprotein Cholesterol and Dementia Risk over 17 Years of Follow-up among Members of Large Health Care Plan.”
“The elevation in dementia risk with both high and low levels of HDL cholesterol was unexpected, but these increases are small, and their clinical significance is uncertain,” said epidemiologist Maria Glymour, ScD (above), study author and Professor of Epidemiology and Biostatistics at UCSF School of Medicine, in a news release. This is another example of how researchers are associating common biomarkers tested regularly by clinical laboratories with additional health conditions and disease states. (Photo copyright: University of California San Francisco.)
HDL Levels Link to Dementia Risk
The UCSF researchers used cholesterol measurements and health behavior questions as they tracked Kaiser Permanente Northern California health plan members who were at least 55 years old between 2002 and 2007, and who did not have dementia at the time of the study’s launch.
The researchers then followed up with the study participants through December 2020 to find out if they had developed dementia, Medical News Today reported.
“Previous studies on this topic have been inconclusive, and this study is especially informative because of the large number of participants and long follow-up,” said epidemiologist Maria Glymour, ScD, study author and Professor of Epidemiology and Biostatistics at UCSF School of Medicine, in the AAN news release. “This information allowed us to study the links with dementia across the range of cholesterol levels and achieve precise estimates even for people with cholesterol levels that are quite high or quite low.”
According to HealthDay, UCSF’s study findings included the following:
- More than 25,000 people developed dementia over about nine years. They were divided into five groups.
- 53.7 milligrams per deciliter (mg/dL) was the average HDL cholesterol level, amid an optimal range of above 40 mg/dL for men and above 50 mg/dL for women.
- A 15% rate of dementia was found in participants with HDL of 65 mg/dL or above.
- A 7% rate of dementia was found in participants with HDL of 11 mg/dL to 41 mg/dL.
“We found a U-shaped relationship between HDL and dementia risk, such that people with either lower or higher HDL had a slightly elevated risk of dementia,” Erin Ferguson, PhD student of Epidemiology at UCSF, the study’s lead study author, told Medical News Today.
What about LDL?
The UCSF researchers found no correlation between low-density lipoprotein (LDL)—often referred to as “bad” cholesterol”—and increased risk for dementia. But the risk did increase slightly when use of statin lipid-lowering medications were included in the analysis.
“Higher LDL was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL was associated with a slightly greater risk of Alzheimer’s disease-related dementia for statin users,” the researchers wrote in Neurology.
“We found no association between LDL cholesterol and dementia risk in the overall study cohort. Our results add to evidence that HDL cholesterol has similarly complex associations with dementia as with heart disease and cancer,” Glymour noted in the AAN news release.
Australian Study also Links High HDL to Dementia
A separate study from Monash University in Melbourne, Victoria, Australia, found that “abnormally high levels” of HDL was also associated with increased risk for dementia, according to a Monash news release.
The Monash study—which was part of the ASPREE (ASPpirin in Reducing Events in the Elderly) trial of people taking daily aspirin—involved 16,703 Australians and 2,411 Americans during the years 2010 to 2014. The researchers found:
- 850 participants had developed dementia over about six years.
- A 27% increased risk of dementia among people with HDL above 80 mg/dL and a 42% higher dementia risk for people 75 years and older with high HDL levels.
These findings, Newsweek pointed out, do not necessarily mean that high levels of HDL cause dementia.
“There might be additional factors that affect both these findings, such as a genetic link that we are currently unaware of,” Andrew Doig, PhD, Professor, Division of Neuroscience at University of Manchester, told Newsweek. Doig was not involved in the in the Monash University research.
Follow-up research could explore the possibility of diagnosing dementia earlier using blood tests and new biomarkers, Newsweek noted.
The Australian researchers published their findings in The Lancet Regional Health-Western Pacific titled, “Association of Plasma High-Density Lipoprotein Cholesterol Level with Risk of Incident Dementia: A Cohort Study of Healthy Older Adults.”
Cholesterol Lab Test Results of Value to Clinical Labs
If further studies validate new biomarkers for testing and diagnosis, a medical laboratory’s longitudinal record of cholesterol test results over many years may be useful in identifying people with an increased risk for dementia.
Clinical pathologists and laboratory managers will want to stay tuned as additional study insights and findings are validated and published. Existing laboratory testing reference ranges may need to be revised as well.
As well, the findings of this UCSF research demonstrate that, in this age of information, there will be plenty of opportunities for clinical lab scientists and pathologists to take their labs’ patient data and combine it with other sets of data. Digital tools like artificial intelligence (AI) and machine learning would then be used to assess that large pool of data and produce clinically actionable insights. In turn, that positions labs to add more value and be paid for that value.
—Donna Marie Pocius