Fluctuating LDL cholesterol affects older adults' cognitive function

Greater visit-to-visit variability of low-density lipoprotein (LDL) cholesterol is associated with lower cognitive performance in a study of older adults, according to an article published online July 19, 2016 in the journal Circulation.

“Our findings suggest for the first time that it’s not just the average level of your LDL cholesterol that is related to brain health, but also how much your levels vary from one measurement to another,” said lead study author Roelof Smit, MD, a PhD student at Leiden University Medical Center in Leiden, the Netherlands. 

Dr. Smit and colleagues found that LDL variability was not only associated with immediate and delayed memory-related outcomes, but also linked to lower measures of selective attention and processing speed. For example, study participants with the highest LDL cholesterol variability took an average 2.7 seconds longer to finish a test of selective attention (the Stroop Color and Word Test) compared with individuals who had the lowest variability.

“While this might seem like a small effect, it is significant at a population level,” Dr. Smit said.

An MRI substudy found that greater LDL variability was also associated with lower cerebral blood flow and greater white matter hyperintensity load, which has been linked to endothelial dysfunction.

Whether patients took statins had no effect on the outcome, nor did a patient’s average level of LDL cholesterol. The association was also independent of patients’ known cerebrovascular and cardiovascular disease and comorbidities.

In conducting this study, researchers included 4,428 participants in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), ages 72 to 80, who lived in Scotland, Ireland, and the Netherlands. Participants had either preexisting vascular disease or were at a higher risk for developing it due to a history of hypertension, cigarette smoking, or diabetes.

The researchers defined LDL cholesterol variability as the intra-individual standard deviation over four LDL cholesterol measurements after baseline. They tested participants using four assessments of cognitive function—a selective attention test, a processing speed test, and two tests of memory (both immediate recall delayed recall)—and looked for associations with LDL variability.

Results showed that patients with greater variability of LDL cholesterol tended to have comparatively lower scores of cognitive performance.

This finding calls to mind previous research that found associations between blood pressure variability and neurocognitive function, the researchers noted. It also raises the question of whether loss of physiological homeostasis could lead to neurocognitive decline through parallel pathophysiological pathways.

“These results add an important puzzle piece to the emerging evidence that vascular risk factors are closely related to brain health,” Dr. Smit said.  “Our study is just the first exciting step. Further studies are needed to examine whether these findings could truly influence clinical practice.”

The study was funded by Bristol-Myers Squibb.