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abstract & commentary
Synopsis: The study demonstrated that individuals 50 years
of age and older who were prescribed statins had a substantially lower risk of developing dementia independent of the presence or absence of untreated hyperlipidemia or the exposure to nonstatin lipid-lowering agents.
Source: Jick H, et al. Lancet. 2000;356:1627-1631.
Cognitive impairment in elderly people, also known as senile dementia, is a heterogeneous condition that in most cases has pathological and clinical features consistent with Alzheimer’s disease (AD).1 There is evidence to suggest a relationship between lipids and vascular changes involving the brain in patients with dementia, although the precise mechanism is poorly understood at the present time.2-5
Jick and associates from the Framingham Heart Study, Boston University, and the Department of Epidemiology of the Harvard School of Public Health evaluated information obtained from 368 practices which contributed data to the UK-based General Practice Research Database. Patients 50 years of age and older were separated into three groups: group 1 consisted of all individuals with a clinical diagnosis of untreated hyperlipidemia, group 2 included those individuals who received lipid-lowering agents, and group 3 consisted of all cases with a computer-recorded clinical diagnosis of dementia. The study demonstrated that individuals 50 years of age and older who were prescribed statins had a substantially lower risk of developing dementia independent of the presence or absence of untreated hyperlipidemia or the exposure to nonstatin lipid-lowering agents.
Comment by Harold L. Karpman, MD, FACC, FACP
Dementia effects an estimated 10% of the population older than 65 years of age. As many as 90% of the patients diagnosed with either dementia or AD by the database practitioners in the United Kingdom were found on detailed analysis to have progressive dementia.6 The Jick et al study of this data clearly demonstrated that patients in the United Kingdom who were prescribed statin drugs had a risk of clinically diagnosed dementia that was 30-70% lower than those individuals who do not have hyperlipidemia and were not put on lipid-lowering drug therapy. The statin drugs themselves, therefore, appear to reduce the risk of dementia although one cannot exclude the possibility that some of the characteristics of the statin recipients not measured in this study may be associated with a lowered risk of dementia.
Statins are known to competitively inhibit the synthesis of cholesterol thereby preventing the conversion of 3hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) to mevalonate. They also reduce the formation and entry of LDL cholesterol into the circulation, upgrade LDL receptor activity, lower serum LDL cholesterol and triglycerides, and increase HDL cholesterol.7 Statins also apparently have beneficial effects on the microvasculature which may be of major importance since some investigators have suggested that cerebral perfusion is decreased in affected areas of the brain in patients with AD. Statins may improve cerebral perfusion both because of specific beneficial effects of these drugs on the cerebral capillary endothelium as well as other properties of the agents. A second question addressed by the study was whether the positive effects of the statin drugs in the treatment of dementia might also be noted when using statin drugs in the treatment for other dementing disorders. Jick et al, therefore, determined the relative risk of dementia in the group diagnosed as "dementia" compared with those diagnosed as "Alzheimer’s disease" and found no material difference in drug effect suggesting that there may be a common risk factor for dementia which is positively effected by statin drug therapy.
The base population in the study consisted of 24,480 individuals who were users of lipid-lowering agents, 11,421 patients with a diagnosis of hyperlipidemia who did not receive lipid-lowering agents, and 25,000 patients who did not receive lipid-lowering agents and did not have a recorded diagnosis of hyperlipidemia. Despite the significantly large number of patients in the three examined groups, it is important to recognize that Jick et al’s study is a purely observational study, and that its results correlated well with findings of another recently published study on this subject.8 The positive findings of these two studies suggest that the use of statins may significantly reduce the risk of dementia in the elderly either by delaying its onset or by stabilizing (or even reversing) specific or general age-related changes that result in cognitive impairment. It is therefore critically important that additional well designed, double-blind, placebo-controlled studies of an acceptable size be mounted as soon as possible since most clinicians would almost certainly recommend statin therapy to broad segments of their patient population if these studies demonstrated the unequivocal efficacy of the statins in preventing senile dementia.
1. Brayne C, et al. Br J Psychiatry. 1995;167:255-262.
2. Saunders A, et al. Neurology. 1993;43:1467-1472.
3. Hofman A, et al. Lancet. 1997;349:151-154.
4. Snowden D, et al. JAMA. 1997;277:813-817.
5. Hyman B, et al. Arch Neurol. 2000;57:646-650.
6. Seshardi S, et al. Arch Neurol. 2001. In press.
7. Knopp R. N Engl J Med. 1999;341:498-511.
8. Wolozin B, et al. Arch Neurol. 2000;57:1439-1443.