Low cholesterol linked to reduced cognitive function

March 23, 2005

Boston, MA - A new study using Framingham Heart Study data has shown a link between low naturally occurring cholesterol levels and poorer cognitive performance.[1]

The study, published recently in the January-February 2005 issue of Psychosomatic Medicine, was conducted by researchers from Boston University. Their major finding is that naturally occurring total cholesterol levels below 200 mg/dL were associated with modestly but statistically significantly worse mental function in areas such as visual organization, memory, attention, and concentration.

But the authors themselves and several outside commentators all stress that there is no evidence of any causal association at this point and that the observation found in this study should not have any clinical impact on the use of cholesterol-lowering drugs.

The current study involved 789 men and 1105 women from the Framingham original cohort who were free of dementia and stroke, received biennial measurements of total cholesterol over a 16- to 18-year period, underwent cognitive testing at the end of the study. Fewer than 2% of the participants were treated with cholesterol-lowering medication.

Results showed that after controlling for many other variables, there was a significant positive linear association between total cholesterol and measures of verbal fluency, attention/concentration, abstract reasoning, and a composite score measuring multiple cognitive domains.

Odds ratios for poorer performance by low total-cholesterol group (<200 mg/dL) relative to the high total-cholesterol group (>240 mg/dL)

Measure Cognitive performance below 33rd percentile   Cognitive performance below 10th percentile  
  Odds ratio p Odds ratio p
Similarities 1.44 0.06 2.17 0.01
Word fluency 1.76 0.002 1.84 0.02
Attention/concentration 1.45 0.06 2.24 0.004
Total composite 1.49 0.03 1.80 0.03
Odds ratios are adjusted for the following covariates: age, gender, education, occupation, cigarettes/day, alcohol consumption, body-mass index, mean arterial pressure, type 2 diabetes, cardiovascular disease, cardiovascular drugs, psychoactive drugs, other drugs, cholesterol-lowering drugs, and cholesterol-lowering diet.
Conflicting results

Lead author Dr Penelope Elias told heartwire that previous studies have shown conflicting results regarding cholesterol and cognitive function, but one study published last year showed similar results to the current study.[2] In addition, she cited two studies of statins that have shown "fairly minor detrimental cognitive effects" associated with the drugs.[3,4]

Current study coauthor Dr Merrill Elias commented to heartwire : "I don't think we can say that our study has defined anything, but there are other data coming out that support our findings. I'm sorry if the cardiologists are not applauding us, but we've got an obligation to report our data."

Can't generalize to drug treatment

The researchers point out that cholesterol is important for brain development in infants and plays a role in neuronal activity in adults, but they add that these results should not discourage people who have been prescribed statins from taking them.

"The result of lowering cholesterol with current medications may be very different from naturally low cholesterol. We certainly need to evaluate what effect lowering cholesterol with medication will have. We can't yet generalize the results of our study to people treated with cholesterol-lowering drugs," Elias said, adding, "I myself am taking a cholesterol-lowering drug, but I'm not going to stop it because of the proven benefits on heart disease."

He also noted that the current study did not look at individual components of cholesterol. "Researchers must next consider individual elements of total blood cholesterol, such as LDL, HDL, triglycerides, etc, and whether one or more of these elements is responsible for the results."

No evidence for causal link

When asked for a comment on the current results, Dr Chris O'Donnell (associate director of the Framingham Heart Study, National Heart, Lung, and Blood Institute), who was not involved in this analysis, said that no firm conclusions could be drawn from this cross-sectional study. He said he agreed with the statement in the paper by the authors: "We cannot specify a causal relationship between total cholesterol levels and cognitive performance."

O'Donnell commented to heartwire that it was well known that patients with cognitive dysfunction are often frail and have comorbid conditions that may lead to poor nutrition and a lower cholesterol. "Low cholesterol could just be a marker of poor cognition. The observation found in this study deserves further study but by itself is insufficient to change current guidelines about the use of cholesterol-lowering medication in elderly patients," he added.


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