Link Between Statins and Cognition Gets More Complicated

Pauline Anderson

November 14, 2007

November 14, 2007 — New research links statin use to reduced cognitive decline, but it uncovers a curious phenomenon: African American patients who stopped taking statins appeared to reap an even greater cognitive benefit than those who continued taking this cholesterol-lowering medication.

The findings, published in the November 6 issue of the journal Neurology, seem to underline the complex nature of the relationship between statins and dementia prevention, the researchers, with senior author Kathleen S. Hall, PhD, a psychiatric epidemiologist and associate professor of psychiatry at the Indiana University School of Medicine, in Indianapolis, write.

Statins play an important role in the prevention of cardiovascular disease (CVD), and given the apparent link between CVD risk factors and risk factors for cognitive decline, it is possible that statins could also play a role in prevention of dementia, the authors conclude.

"However, given the inconsistency of the results of statin use on cognitive function from observational studies and the complexities involved in interpreting the results of these studies, it is likely that only carefully designed randomized clinical trials of statins will provide definitive answers to their potential role in dementia prevention," they write.

Evaluating the Role of Statins

In 2001 and again in 2004, researchers at Indiana University School of Medicine and Regenstrief Institute, also in Indianapolis, evaluated the cognitive status of 1146 African Americans aged 70 years and older living in Indianapolis, Indiana as part of the Indianapolis-Ibadan Dementia Project. Cognitive assessment included tests of language, attention, calculation, memory, and orientation. Participants provided blood samples for ApoE genotyping and were also assessed for a number of risk factors, including smoking, alcohol use, and social involvement.

The researchers also evaluated statin use. They noted that 25% of the elderly African American sample were using statins in 2001, perhaps not surprising since African Americans have a higher prevalence of coronary risk factors than other populations in the United States.

Adjusting for age at baseline, sex, education, and ApoE status, researchers found less cognitive decline among statin users than among non–statin users.

On the standardized cognitive change scores, statin users had a mean change of -0.14 SD, while non–statin users had a mean change of 0.05 SD, a difference of 0.19 SD after adjustment for age at baseline, sex, education, and ApoE status. Logistic regression showed statin use may also be associated with less incident dementia (OR, 0.32; P = 0.0673).

If statin use reduces cognitive decline, then it is reasonable to assume that continued use of statins would produce a greater reduction. However, that was not the case in this study. Researchers found that 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.

"When the 3 groups of statin users (statin use at both baseline and follow-up; statin use only at baseline; and statin use only at follow-up) are compared separately with the non–statin users at either wave, a significant inverse association for cognitive decline was seen only in the group that was using statins at baseline but had discontinued use at follow-up," the authors write.

Participants who had stopped using statins by the 2004 evaluation had similar health, demographic, clinical, and biochemical characteristics as those who continued using the drug.

Researchers were "surprised" by these findings, they say. Neither the lipid-lowering nor the anti-inflammatory effects of statins could explain the effect of statins on cognitive decline, Dr. Hall told Medscape Psychiatry.

They included measurements of lipids (low-density lipoprotein cholesterol [LDL-C]) and inflammation (C-reactive protein [CRP], an inflammatory marker for CVD) in their predictive models and found no interactions between LDL-C or CRP and statin use. "Statin use remained significantly associated with cognitive decline," the authors write.

Since the study did not collect information on the compliance, duration, or dosage of statin use, "it is possible, if perhaps unlikely, that the statin users who had discontinued use at follow-up had in fact longer exposure to statins than the other statin user groups," the authors write.

It is possible that some other mechanism of statins — for example, their antioxidant effects or protective effect on endothelial dysfunction — is at work, said Dr. Hall. "We intend to explore these possibilities in future studies," she said.

In addition to lowering lipids in plasma, statins also lower the level of a major product of brain cholesterol metabolism. "Statin use plays an important role in the prevention of cardiovascular disease," Dr. Hall said in a press release. "And there may be a link between cardiovascular risk factors and risk factors for cognitive decline and Alzheimer's disease."

The study was funded by the National Institute on Aging. The authors report no conflicts of interest.

Neurology 2007;69:1873-1880. Abstract

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