Low LDL cholesterol associated with worse cognitive performance

Summary: cholesterol plays critical roles in cell membranes and steroid hormone production. This study associates low LDL cholesterol with worse cognitive performance. As expected, the effect is amplified by inflammation. Care should be taken to apply a balanced approach to cholesterol lowering therapies.

A truly fascinating study was just published in the journal Neurobiology of Aging investigating lipoproteins and loss of cognitive function. The authors state:

“The aim of this study was to examine the associations between high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, and cognition and focus on the modifying effect of inflammation.”

They collected biological and cognitive data on 1003 persons ≥ 65 years of age over 6 years of follow-up, measuring cognition with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), and Coding Task (information processing speed). High HDL was associiated with better memory performance, but their data seem to suggest the importance of sufficient LDL cholesterol in brain neuronal membranes:

“We found an independent association between high HDL cholesterol and better memory performance. In addition, low LDL cholesterol was predictive of worse general cognitive performance and faster decline on information processing speed.”

Not at all surprisingly they found that inflammation compounds the adverse effects of low LDL:

“Furthermore, a significant modifying effect of inflammation (C-reactive protein, α-antichymotrypsin) was found. A negative additive effect of low LDL cholesterol and high inflammation was found on general cognition and memory performance.”

And since high triglycerides are commonly provoked by the high insulin levels due to insulin resistance which also have deleterious effects on the brain…

“Also, high triglycerides were associated with lower memory performance in those with high inflammation.”

The authors conclude by suggesting that HDL, LDL and inflammatory indicators can be used as predictors of poor cognitive function:

“Thus, a combination of these factors may be used as markers of prolonged lower cognitive functioning.”

This compels us to use caution and see the ‘big picture’ when designing strategies to manage lipids—care should be taken to not suppress LDL cholesterol to too low a level.

Cholesterol levels vary with the menstrual cycle

A study recently published in The Journal of Clinical Endocrinology & Metabolism proves that we must take the menstrual cycle into consideration when testing cholesterol in cycling women.

“The objective of the study was to evaluate the association between endogenous [internally produced] estrogen and serum lipoproteins across the menstrual cycle.”

The authors found that total and LDL cholesterol were lower during the luteal phase (second half, when progesterone is higher) than the follicular phase:

More women were classified above the desirable range (LDL ≥130 mg/dl or total cholesterol ≥200 mg/dl) when measured during the follicular phase [first half].”

HDL was higher when estradiol had peaked, corresponding also to lower LDL and triglycerides.

Because lipoprotein cholesterol levels vary across the menstrual cycle, cyclic variations in lipoprotein levels may need to be considered in the design and interpretation of studies in reproductive-age women and in the clinical management of women’s cholesterol.

Lipid assessment for risk of vascular disease gets easier and cheaper

This study recently published in the Journal of the American Medical Association analyzed the records of 302,430 people included in 68 long-term studies, with 2.79 million person-years of follow-up. The surprising finding is that measuring only total cholesterol plus HDL cholesterol OR apolipoproteins, without the need to fast, was as accurate as more elaborate and costly investigations. The authors state: “Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.”