Low Cholesterol and Cognitive Problems

dr_duane_graveline_m.d._134By Dr. Duane Graveline, M.D., M.P.H.

"Brain fog" when on statins has been widely reported and is one of the more common side effects. Do not let your doctor tell you it does not happen. Some researchers say the incidence of statin associated cognitive adverse effect is near 100% if sufficiently sensitive testing methods are used.

But it is not only those that take statins to lower their cholesterol that face cognitive impairment issues, people with naturally low levels of cholesterol also demonstrate poorer performance on a variety of cognitive tests. Researcher Penelope K. Elias MD of Boston University reported this in a study published in Psychosomatic Medicine (1).

In this study, data was analyzed from 789 men and 1,105 women to examine the relationship between total cholesterol and cognitive performance. They found that those who had the lowest total cholesterol performed more poorly on tests of word similarities, word fluency and attention and concentration ability than patients with higher cholesterol levels. "It is not entirely surprising that lower cholesterol levels were associated with moderately lower levels of cognitive function given that cholesterol is important in brain function," reported lead study author, Doctor Elias.

"The differences were not small," she reported. Those in the lowest total cholesterol group (a cholesterol level of under 200) were 49 percent more likely to perform poorly and 80 percent more likely to perform very poorly than were participants in the highest total cholesterol group (240 to 380). ( For conversion of cholesterol values, use this link: Cholesterol Converter ).

The study was performed with people who had naturally low levels of cholesterol and were not being treated with anti-cholesterol drugs. "Naturally low levels of cholesterol and lowered levels of cholesterol may have very different ramifications for cognitive function," Elias said.

Others have found that low serum cholesterol as a result of statin drug use is also associated with cognitive dysfunction. On their review of some 25,000 adverse drug reports taken from U.S. Food and Drug Administration's (FDA) Medwatch repository, Wagstaff and others discovered hundreds of reports of statin associated cognitive dysfunction such as extreme forgetfulness, confusion and disorientation in these statin users (2). Their report of 60 cases of statin associated memory loss was published in Pharmacotherapy, July 2003, It was the first significant report of this subject in the medical literature.

In my own review of the Medwatch data for the period 1999 through 2006, I found 662 reports of atorvastatin ( Lipitor® ) associated transient global amnesia and severe memory loss. Like Wagstaff, I did not report on the lesser forms of cognitive loss such as confusion, disorientation and forgetfulness co-existing with the more significant cognitive manifestations (3).

399 of the reports were for amnesia and 263 were for memory impairment. These amnesia and memory impairment reports increased every year from 1997 through 2006 which paralleled the steady increase in dosage of atorvastatin from an average of 15mg/day in 1997-2001 to an average of 22mg/day by 2006.

Matthew Muldoon and others conducted two separate studies on cognitive consequences of induced cholesterol lowering, the first with lovastatin ( Mevacor® ) and the second with simvastatin ( Zocor® ).

In the first of his double blind placebo controlled trials, Muldoon assessed cognitive function and psychological well being in a group of healthy adults (4). Subjects were 24 to 60 years old and had LDL cholesterol levels of 160 mg/dl or higher. Each subject was randomly assigned to receive 20 mg/day of lovastatin or placebo for 6 months.

Serum lipid levels were measured throughout the study. At baseline and at completion of treatment, comprehensive neuropsychological tests were conducted for attention (digit vigilance, letter rotation, digit span, recurring words), psychomotor speed (grooved pegboard, maze, digit symbol), mental flexibility (strobe interference, trail making, digital vigilance, letter rotation), working memory (associated learning, digit span), memory retrieval (controlled word association, and digit symbol recall, verbal recall, complex figure).

Psychological well being was assessed by daily diaries and subject interviews. At 6 month follow up, the placebo group had improved in a statistically significant manner in all five domains of cognitive function.

Three years later Muldoon and his group repeated this study using simvastatin. The results were similar to the lovastatin study ( 5 ).

Failure of many if not most practicing physicians to recognize statin associated cognitive disturbance is clearly evident among the many published, peer reviewed studies involving tens of thousands of patients where significant adverse cognitive effects are consistently denied.

FDA's own pre-release study of Lipitor documented that 4 to 5 cases of significant cognitive impairment such as amnesia or memory loss would be expected per 1,000 users of the drug. This information was obtained during the clinical evaluation phase of Lipitor where 2,504 volunteers were given varying doses of this drug and followed for one year. During this time all lesser forms of cognitive loss such as confusion, disorientation or forgetfulness were disregarded.

Cognitive impairment may not always be apparent in affected statin users. Often these effects are subtle and difficult to pinpoint or measure. Our brains are not precise instruments and substantial decrement can be present without being evident either to the person or observers.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

1. http://www.psychosomaticmedicine.org/content/67/1/24.abstract
2. http://www.ncbi.nlm.nih.gov/pubmed/12885101
3. http://www.spacedoc.com/662_cases_memory_loss
4. http://www.ncbi.nlm.nih.gov/pubmed/10806282
5. http://www.ncbi.nlm.nih.gov/pubmed/15589485

Updated October 2011

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