​​Statins and the association with survival, risk of ischemic stroke and cognition in patients with dementiaPetek Martinčič, Bojana (Avtor) Gregorič Kramberger, Milica (Mentor) Garcia Ptacek, Sara (Komentor) Winblad, Bengt (Komentor) dementiaAlzheimer’s diseaseHMG-CoA reductase inhibitorsstatinsischemic strokemortalitycognitive declineBackground: Midlife hypercholesterolemia is linked to an increased risk of Alzheimer’s dementia (AD) and ischemic stroke, and dysregulated brain cholesterol homeostasis may contribute to AD pathogenesis. Statins, used for cardiovascular and cerebrovascular disease prevention, may affect cognitive functions. However, evidence on the effects of statins on mortality and stroke risk in dementia patients remains limited due to underrepresentation in clinical trials. Additionally, studies examining the relationship between statins and cognitive decline have produced inconsistent findings. Objective: To study the prescription patterns of statins in patients, included in the Swedish registries, and evaluate possible differences of statin prescription in patients with dementia. To compare the patients with dementia who received statins to patients with dementia who were not treated with statins and evaluate their risk of (1) death (2) ischemic stroke and (3) the association between the use of statins and cognitive decline after dementia diagnosis. Hypotheses: (1) Statins lower the risk of death in patients with dementia. (2) Statins lower the risk of ischemic stroke in patients with dementia. (3) Statin use is associated with a slower cognitive decline in patients with dementia. Methods: Three cohort studies examined the relationship between statin use, survival, ischemic stroke, and cognitive function in patients with dementia, using Swedish national registries. First study: Propensity score-matched parametric and Cox regression models estimated associations between statin use, all-cause mortality, and first ischemic stroke, presenting hazard ratios (HR) with 95% confidence intervals (CI). Second study: Cognitive trajectories based on Mini-Mental State Examination (MMSE) scores of statin users and non-users were compared through mixed-effect regression models with inverse probability of drop-out weighting, including dose-response analysis and comparisons of different statin groups. Third study: Multivariable and linear regression models explored factors influencing simvastatin and atorvastatin prescriptions, serum cholesterol levels, and baseline MMSE scores. Results: The first study revealed that statin use in dementia patients was associated with lower risks of all-cause mortality and ischemic stroke compared to non-users. Stratified analysis revealed a more pronounced, significant protective association between statin use and mortality in men, patients older than 75 years, and patients with AD and vascular dementia. For stroke, the association was significant in men, patients older than 75 years, patients with mixed dementia. There was also a graded reduction in mortality with higher cumulative statin doses. The second study showed a dose-response effect of statins on cognitive decline in AD or mixed dementia patients, with statin use linked to better cognitive scores (measured by MMSE) over three years, especially among simvastatin users compared to other statins. The third study evaluated factors influencing statin prescriptions in AD patients. Statin prescription was more likely in patients with diabetes, ischemic heart disease, or stroke. Older patients were less likely to be prescribed statins. Simvastatin users showed higher baseline cognitive scores compared to non-users of statins. In non-users, higher LDL cholesterol, total cholesterol, and HDL cholesterol levels correlated with better baseline cognitive scores. Conclusions: The use of statins showed benefit for the survival and ischemic stroke risk in patients with dementia in a dose-dependent manner. Patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment. Younger patients and those with cardiovascular disease were more likely to receive statins. Simvastatin use was linked to higher cognitive scores at diagnosis compared to non-use. Higher cholesterol levels were linked to better cognitive scores in non-users of statins.20262026-05-13 07:15:09Doktorsko delo/naloga182468VisID: 39058sl