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

Author:

Petek Bojana,Häbel Henrike,Xu Hong,Villa-Lopez Marta,Kalar Irena,Hoang Minh Tuan,Maioli Silvia,Pereira Joana B.,Mostafaei Shayan,Winblad Bengt,Gregoric Kramberger Milica,Eriksdotter Maria,Garcia-Ptacek Sara

Abstract

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.

Funder

Stiftelsen Dementia

Margaretha af Ugglas Foundation

Health, Medicine and Technique grants from the Stockholm Region and Kungliga Tekniska Högskolan

Johanniterorden i Sverige/Swedish Order of St John

Medicinska Forskningsrådet

Karolinska Institutet Research Foundation

Karolinska Institutet Foundation for Diseases of Aging

The Erling Persson foundation

New Innovative Research grants

Innovative ways to fight Alzheimer´s disease - Leif Lundblad Family and others

Karolinska Institute

Publisher

Springer Science and Business Media LLC

Subject

Cognitive Neuroscience,Neurology (clinical),Neurology

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