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Variability in LDL cholesterol is linked to poorer cognitive performance in older people

BMJ 2016; 354 doi: (Published 20 July 2016) Cite this as: BMJ 2016;354:i4040
  1. Susan Mayor
  1. London

Greater variability in low density lipoprotein (LDL) cholesterol is associated with poorer cognitive performance in older people, a large international study has shown.1

Researchers assessed the association between variability in LDL cholesterol and tests of cognitive function in 4428 people (aged 70 to 82) with pre-existing vascular disease or at increased risk of vascular disease who were taking part in a prospective randomised trial of pravastatin. They also looked at the impact of LDL cholesterol variability on levels of white matter in the brain by using magnetic resonance imaging scans in a subset of 535 study participants.

LDL cholesterol levels were measured after an overnight fast, and variability was calculated as the standard deviation for a participant’s measurements at baseline and at three, six, 12, and 24 months.

Results showed that people with the greatest variability in LDL cholesterol had significantly lower cognitive test scores, with or without statin treatment. Study participants with the greatest LDL cholesterol variability performed significantly less well in memory tests than those with the least variability (immediate recall P=0.002 in the placebo group and P=0.006 in the statin group; delayed recall P=0.001 and P<0.001, respectively).

Patients with the highest LDL cholesterol variability took an average of 2.7 seconds longer to finish a cognitive test than those with the lowest variability.

“While this might seem like a small effect, it is significant at a population level,” said the lead author, Roelof Smit, of Leiden University Medical Center in the Netherlands. “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.”

Results from brain scans showed that higher LDL cholesterol variability was associated with greater white matter hyperintensity load (areas of high intensity that occur with ageing and some illnesses) in patients treated with a statin (P=0.046) but not in the placebo group (P=0.184). Higher variability in LDL cholesterol was also associated with lower total cerebral blood flow in both groups of patients (P=0.031 in the placebo group; P=0.05 in the statin group).

The researchers said that LDL cholesterol may be causally related to cognitive function, where fluctuations in the composition of atherosclerotic plaques increase the risk of subclinical cerebrovascular damage or because of increasing endothelial dysfunction. Alternatively, the findings may reflect the effects of undetected disease, such as undiagnosed cancer or serious infection, which can result in increased lipid variability and cognitive impairment.

Further studies are needed to explore the association, they concluded.


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