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
Cited by
6 articles.
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