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

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.

Statins, Risk of Death and Ischemic Stroke in Patients with Dementia: A Registry-Based Observational Cohort Study.

BACKGROUND: Survival in patients with dementia is variable. Statins are a cornerstone of cardiovascular prevention. However, the effect of statins on mortality and risk for stroke in patients with dementia is not clear. OBJECTIVE: The aim of the study was to analyse the association between the use of statins and the risk of all-cause death and first ischemic stroke in patients diagnosed with dementia. METHODS: A longitudinal cohort study of 48 771 patients based on combined Swedish registries was conducted. The association between the incident use of statins one year prior to dementia diagnosis, allcause mortality and first ischemic stroke was examined using propensity score-matched flexible parametric or Cox hazard survival models and is presented with hazard ratios and corresponding 95% confidence intervals. RESULTS: After propensity score matching, incident users of statins (n=1412) had a lower risk of all-cause death (HR 0.82, 95% CI 0.74-0.91) and ischemic stroke (HR 0.62, 95% CI 0.43-0.89) compared to matched non-users (n=4482). In stratified analysis, the protective association between incident statin use and survival was observed in men, patients older than 75 years, with Alzheimer's disease and vascular dementia. Furthermore, we observed a protective association between incident use of statins and first ischemic stroke risk in men, patients older than 75 years and with mixed dementia. There was a graded association between cumulative doses of statins and mortality. CONCLUSION: The use of statins might be beneficial for the survival and ischemic stroke risk in patients with dementia in a dose-dependent manner.