Statins May Decrease Dementia Risk
Statins May Decrease Dementia Risk
Source: Jick H, et al. Lancet 2000;356:1627-1631.
Jick and colleagues, studying the records of thousands of patients in Great Britain, found preliminary evidence that lipid-lowering statin medications may decrease the risk of developing dementia. The study was motivated by emerging evidence that the processing of certain lipids may play a role in the pathogenesis of Alzheimer’s Disease (AD), as well as vascular dementia.
The study involved a case-control analysis of dementia cases and matched controls in the UK-based General Practice Research Database. This registry is derived from the medical practices of 368 general physicians who have contributed data for more than 3 million patients since 1987. Jick et al selected 284 cases of newly-diagnosed dementia, and 1080 nondemented controls that were most suitable to the purposes of their study.
Factors found to be associated with an increased risk of dementia in this patient cohort included smoking, history of coronary artery bypass surgery, and a low body mass index. Dementia was documented in only 13 patients currently using statins. Adjusting for age, gender, smoking history, vascular risks, and other possible contributing factors, the relative risk of developing dementia among current statin users was 0.29 (0.13-63%), representing a statistically significant 71% risk reduction. In contrast, the risk of dementia in patients with untreated hypertension and in patients taking other, non-statin lipid-lowering medications was not significantly different from controls. There was no significant difference in the effects of statins on men vs. women, or as a function of age.
Jick et al acknowledge that there are certain limitations to their analyses, including the lack of formal confirmation of the dementia diagnoses and the lack of available information on the nature of the hyperlipidemia or the response to medication. Nevertheless, they state that the data are compelling enough to warrant studies of the possible protective effects of statins against dementia be carried out urgently.
Comment by Norman R. Relkin, MD, PhD
This report of a possible effect of statins (HMGCoA reductase inhibitors) on reducing the risk of dementia is certainly noteworthy. Statins are widely available, generally well-tolerated and effective as lipid-lowering agents, traits that would seem desirable in a potential dementia preventative intervention. However, one must be cautious about drawing far-reaching conclusions from this single observational epidemiological study. Although the case-control design reduces the likelihood of spurious associations, other explanations of the data are conceivable that would not necessarily support a protective effect of statins. For example, similar odds ratios might result if the physicians who prescribe statins happen to be less prone to diagnose dementia, or more prone to take other steps that reduce the risk of dementia. The accuracy of the dementia diagnosis in this study must also be questioned because the data set derives from busy physicians in general medical practice, a context in which dementia has been shown to be under-recognized and inaccurately diagnosed.
Past studies have failed to show a convincing correlation between cholesterol levels and risk of AD, and the present study leaves open the question of whether statins might mediate protective effects through actions on systemic lipids or other biological effects. The use of statins in patients with hyperlipidemia may be justified irrespective of whether there is definitive evidence of dementia protective effects. However, prospective studies must be carried out before statins could be recommended for the specific indication of affording protection against dementia.
Dr. Relkin is Associate Professor of Clinical Neurology and Neuroscience, New York Presbyterian Hospital-Cornell Campus, New York, NY.
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