Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people

Arch Neurol. 2002 Feb;59(2):223-7. doi: 10.1001/archneur.59.2.223.


Background: Recent reports suggest a possibly protective effect for statins in patients with Alzheimer disease. This association could be due to indication bias, i.e., people who elect to take lipid-lowering agents (LLAs) may be healthier than those who do not, so that it may be these other health factors that explain their lower risk of dementia.

Objectives: To examine the association between the use of LLAs and dementia, adjusting for other markers of health, and to investigate factors associated with LLA use.

Design: A cohort study of LLA use and a case-control study of dementia in relation to LLA use, in a secondary analysis of the Canadian Study of Health and Aging.

Setting: A nationally representative population-based survey of Canadians 65 years and older.

Participants: To examine features associated with statin use, we evaluated data on 2305 people for whom health information, drug use, and cognitive status were known. To examine the relationship between LLA use and dementia, we selected incident cases of dementia (n = 492, of whom 326 had Alzheimer disease) that occurred between the first and second waves of the study. Control subjects were 823 persons examined during the first and second phases of the Canadian Study of Health and Aging who had no cognitive impairment.

Results: Use of LLAs was significantly (P<.001) more common in younger (65-79 years) than in older (> or = 80 years) people. It was not associated with other factors indicating a healthy lifestyle, but was associated with a history of smoking and hypertension. Use of statins and other LLAs reduced the risk of Alzheimer disease in subjects younger than 80 years, an effect that persisted after adjustment for sex, educational level, and self-rated health (odds ratio, 0.26; 95% confidence interval, 0.08-0.88). There was no significant effect in subjects 80 years and older.

Conclusions: While the possibility of indication bias in the original observations cannot be excluded, it was not demonstrated in LLA use in this study. Lipid-lowering agent use was associated with a lower risk of dementia, and specifically of Alzheimer disease, in those younger than 80 years. Further research is warranted.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / prevention & control
  • Bias
  • Case-Control Studies
  • Cohort Studies
  • Epidemiologic Studies
  • Female
  • Humans
  • Hypolipidemic Agents / adverse effects*
  • Hypolipidemic Agents / therapeutic use
  • Incidence
  • Male
  • Risk Factors


  • Hypolipidemic Agents