Study Of Relationship Between Statins And Cognitive Decline

06 Nov 2007
http://www.medicalnewstoday.com/articles/87841.php

Previous explorations of a link between statins, a cholesterol lowering medication, and cognitive decline have produced inconsistent results. New research reveals that the relationship between statin use and cognitive decline appears even more complex than had been thought.

In a three year epidemiological study, researchers from the Indiana University School of Medicine and the Regenstrief Institute, Inc. have found an association of statin use with less cognitive decline in elderly African Americans and report that, surprisingly, the association is even stronger for those who had discontinued use than for continuous users. Their findings are published in the Nov. 6 issue of Neurology.

In 2001 and again in 2004, the IU School of Medicine researchers evaluated 1146 African Americans aged 70 and older living in Indianapolis testing them in various cognitive areas including language, attention and calculation, memory and orientation. The researchers also compared use of statins and whether, if used, they were taken consistently. While cognitive decline in statin users was less than those who did not take statins, those who continued to take statins from 2001 to 2004 had greater cognitive decline than those who were taking statins in 2001 but were no longer taking them in 2004. Study participants who discontinued statin use did not differ from those who continued to use statins in any other health, demographic, clinical or biochemical characteristics.

If statin use were directly associated with a reduction in cognitive decline, continuously taking statins would presumably produce the greatest effect. The study authors say that in light of their findings that the association between statins and decreased cognitive decline is more complex than previously realized, carefully designed randomized clinical trials of statins are needed to provide definitive answers to their potential role in dementia prevention.

"Statin use plays an important role in the prevention of cardiovascular disease. And there may be a link between cardiovascular risk factors and risk factors for cognitive decline and Alzheimer disease. This is just one area that needs to be explored," said Kathleen S. Hall, Ph.D, senior author of the study. A psychiatric epidemiologist, she is an associate professor of psychiatry at the IU School of Medicine and an affiliated scientist of the Regenstrief Institute.

Dr. Hall is the principal investigator of the Indianapolis -- Ibadan comparative epidemiological project, a study designed to identify potentially modifiable risk factors for Alzheimer disease by comparing the disease in two populations from a developed and developing country--African Americans living in Indianapolis and Yoruba living in Ibadan, Nigeria.

"We know that taking statin medication can protect against cardiovascular events such as heart attacks by lowering blood cholesterol. The question at hand is what effects do these medications have on brain function. Our study along with others shows promising results but larger controlled studies are needed," said Stanley Szwast, M.D., a fourth year psychiatry resident at the Indiana University School of Medicine and first author of the study.

I am more than perplexed with the statement in the last paragraph of the article "Our study along with others shows promising results..." how does one spin non continuous use of a drug resulting in greater benefit than continuous use into a "promising result"?
Predictably, initial use of statins should be of benefit in any disease that includes an inflammatory process--as most of all the neurodegenerative diseases are theorized to include. Statins are powerful anti-inflammatory agents, and initially should decrease this aspect of any disease. With continued use, the other "pleiotrophic" effects become evident: these pleiotrophic effects are mainly the result of depression in isoprenoid biosynthesis leading to impairment of the production of a variety of metabolic substrates such as dolichols, crucial for N-linked glycosylation; geranylgeranyl pyrophosphate, necessary for coenzyme Q10; farnesyl-pyrophosphate, necessary for the maturation of prelamin A and B-type lamins and G-proteins ;and isopentenylpyrophosphate, involved in direct modification of selenocysteinyl-tRNA and thus indirectly related to the synthesis of all selenoproteins (last estimated at 35). (glutathione reductase is depleted by statins--this substance is responsible for recycling glutathione in the brain)
Important to remember: brain cholesterol has a half-life of ~5yrs. Fat soluble statins, Lipitor, zocor, crestor, all cross the blood brain barrier and thus are able to affect the level of brain cholesterol. If a critical level of cholesterol exists for the brain, more time than a 2 to 3 yr period normally used in clinical trials would be necessary to appreciate the effects of lowering cholesterol levels in the brain.