Petek B, Sweden; S€ odersjukhuset, Stockholm, Sweden). Connecting the brain cholesterol and reninangiotensin systems: potential role of statins and RAS-modifying medications in dementia (Review). J Intern Med 2018;284: 620-642.Millions of people worldwide receive agents targeting the renin-angiotensin system (RAS) to treat hypertension or statins to lower cholesterol. The RAS and cholesterol metabolic pathways in the brain are autonomous from their systemic counterparts and are interrelated through the cholesterol metabolite 27-hydroxycholesterol (27-OHC). These systems contribute to memory and dementia pathogenesis through interference in the amyloid-beta cascade, vascular mechanisms, glucose metabolism, apoptosis, neuroinflammation and oxidative stress. Previous studies examining the relationship between these treatments and cognition and dementia risk have produced inconsistent results. Defining the blood-brain barrier penetration of these medications has been challenging, and the mechanisms of action on cognition are not clearly established. Potential biases are apparent in epidemiological and clinical studies, such as reverse epidemiology, indication bias, problems defining medication exposure, uncertain and changing doses, and inappropriate grouping of outcomes and medications. This review summarizes current knowledge of the brain cholesterol and RAS metabolism and the mechanisms by which these pathways affect neurodegeneration. The putative mechanisms of action of statins and medications inhibiting the RAS will be examined, together with prior clinical and animal studies on their effects on cognition. We review prior epidemiological studies, analysing their strengths and biases, and identify areas for future research. Understanding the pathophysiology of the brain cholesterol system and RAS and their links to neurodegeneration has enormous potential. In future, well-designed epidemiological studies could identify potential treatments for Alzheimer's disease (AD) amongst medications that are already in use for other indications.2 Promotion of oxidative stress by acting on LRX in astroglia [90,91].Brain cholesterol and RAS in dementia / B. Petek et al.

BackgroundA new project on education in family medicine training was implemented last year in Slovenia by establishing regional coordinators in the specialist training programme. They are responsible for conducting regular small-group meetings with family medicine trainees. This study wanted to explore the attitudes and opinions of regional coordinators and family medicine trainees concerning this new method.MethodsThis was a qualitative study based on focus groups. The participants were regional coordinators and family medicine specialist trainees. The data were analysed based on the principles of thematic content analysis with inductive technique.ResultsThe study revealed five themes which were the same for the analysis of transcripts of both regional coordinators and family medicine trainees: 1) Meetings with trainees; 2) Coordination; 3) Characteristics of regional coordinators; 4) Position of regional coordinators, and 5) Evaluation of regional coordinators.ConclusionParticipants of the study have many expectations for this new programme. They expect progress in trainees’ clinical knowledge through experience-based group learning and with the help of the tutorship role of regional coordinators. The role of regional coordinators represents a new possibility for solving problems in the training programme in their coordinating role. In future, they have the potential to develop into an expert body that supervises the quality of training. A close follow-up is necessary to see if the position of regional coordinators is adequate and if they meet the expectations of the trainees as well as their own goals. Administrative and financial support for the programme is necessary. The project is important also in enabling the adaptation of the training programme’s needs and the regional characteristics of medical care.

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.