Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study

Alzheimers Res Ther. 2023 Dec 20;15(1):220. doi: 10.1186/s13195-023-01360-0.

Abstract

Background: Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer's disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms.

Objective: To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment.

Methods: A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users.

Results: Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent.

Conclusions: Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses.

Keywords: Alzheimer's disease; Cholesterol metabolism; Cognitive impairment; Cohort study; HMG-CoA reductase inhibitors; Statins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / epidemiology
  • Atorvastatin / therapeutic use
  • Cholesterol
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Longitudinal Studies
  • Mixed Dementias*
  • Simvastatin / therapeutic use

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin
  • Simvastatin
  • Cholesterol