Effect of Statins on Cognitive Decline and Dementia in Older Adults

Quick Takes

  • In this large, prospective cohort study, statin use was not associated with incident dementia, mild cognitive impairment, or cognitive decline.
  • No differences were found in any of the primary outcomes between users of hydrophilic versus lipophilic statins.
  • These results are encouraging, but a randomized trial with dementia and cognitive decline as prespecified outcomes will be required to prove that statins do not worsen cognitive outcomes.

Study Questions:

Is there an association between baseline statin use and incident dementia and cognitive decline?

Methods:

This is a substudy of a larger prospective cohort study of 18,846 participants ≥70 years (≥65 years if US minorities) with no prior cardiovascular events or dementia recruited in Australia (87%) or the United States (13%). Participants were grouped by their baseline statin use (yes/no). Given a possible increased effect of lipophilic (fat soluble) statins on cognition, comparisons were performed between subjects on hydrophilic statins (pravastatin and rosuvastatin) versus lipophilic statins (atorvastatin, simvastatin, fluvastatin, lovastatin, pitavastatin). The primary outcomes were incident dementia, incident mild cognitive impairment (MCI), and change in cognitive function over time (assessed at years 1, 3, 5, and at final visit).

Results:

Of the 18,846 participants, 5,898 (31.3%) were taking statins at baseline. At baseline, statin users were more likely than nonusers to be women, to have <12 years’ education, and to have obesity, chronic kidney disease, diabetes, and hypertension. During follow-up, 566 incident cases of dementia and 380 incident cases of MCI were identified. Statin use was not associated with incident dementia (hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.97-1.40) or MCI (HR, 0.97; 95% CI, 0.77-1.22). At baseline, statin users had worse cognitive scores than nonusers. No association between statin use and decline in cognition over time was identified. No differences were found in any of the primary outcomes between users of hydrophilic versus lipophilic statins.

Conclusions:

In this large prospective cohort study of patients without dementia, baseline statin use was not associated with incident dementia or MCI, nor was statin use associated with decline in cognitive function over time. Results did not differ by statin lipophilicity.

Perspective:

These data are encouraging and support prior work that suggests that statin use is not associated with development of dementia, MCI, or cognitive decline over time. However, given that this study is observational in design, the results do not prove that statins do not worsen cognitive outcomes. A randomized trial with dementia and cognitive decline as prespecified outcomes would be required to eliminate potential confounding factors by indication or comorbidity. Subjects in this trial were free of dementia at baseline, so these data do not speak to the possibility that statins worsen pre-existing cognitive impairment.

Clinical Topics: Cardiovascular Care Team, Dyslipidemia, Geriatric Cardiology, Prevention, Nonstatins, Novel Agents, Statins, Hypertension, Sleep Apnea

Keywords: Cognition, Cognition Disorders, Comorbidity, Dementia, Diabetes Mellitus, Geriatrics, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Obesity, Primary Prevention, Renal Insufficiency, Chronic, Vascular Diseases


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