Connecting the brain cholesterol and renin-angiotensin systems: potential role of statins and RAS-modifying medications in dementia.

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.

Clinical and radiological characteristics of tumefactive demyelinating lesions: follow-up study.

BACKGROUND: Demyelinating lesions over 20 mm in size, referred to as tumefactive demyelinating lesions, can be misdiagnosed as being either a tumor or an abscess. Although some radiological characteristics can help make a differential diagnosis easier, a cerebral biopsy may still be necessary. OBJECTIVE: Our objective was to assess the clinical characteristics of tumefactive lesions, with or without a diagnosis of multiple sclerosis (MS), and present follow-up data for 54 patients with tumefactive lesions. METHODS: Demographic, clinical, radiological and laboratory data were gathered and treatment responses were evaluated in a total of 54 patients from five medical centers. RESULT: Twenty-nine patients were diagnosed with tumefactive lesions at the onset, whereas 25 patients were diagnosed with tumefactive lesions after a diagnosis of MS. Median follow-up was 38.12 months. At final examination, 19 of the patients with a tumefactive lesion diagnosis at the onset eventually developed relapsing-remitting MS, while 10 remained with the condition as a clinically isolated syndrome. The tumefactive lesions studied were mostly focal, with closed-ring enhancement. We found that oligoclonal band positivity was less frequent in the patients with tumefactive onset. CONCLUSION: Although our demographic data were similar to formerly collected Turkish MS data, we found that the distribution of the patients' clinical course differed if there was an absence of primary progressive MS and that there was a lower frequency of secondary progressive MS cases in our group of patients. We believe that less frequent oligoclonal band positivity and the difference we witnessed in the clinical course of disease in our study groups suggest that there is a need for further studies to compare all the biological and immunological differences between MS and tumefactive lesion cases, in order to reveal whether there are different pathogenetic mechanisms involved.

[Contrast-enhanced sonography of the liver]. / Kontrastverstärkte Sonographie der Leber.

The detection rate of liver lesions using ultrasonography is 53-77%, rendering this method inferior to CT and MRI. Despite well-known limitations, development of stable second-generation contrast agents in conjunction with new techniques of contrast display has led to increased diagnostic accuracy. Characterization of focal liver lesions with ultrasound contrast agents follows known features of iodine- and gadolinium-containing contrast agents, but compared to CT and MRI sensitive visualization of intratumoral vessels takes place in real time. In addition to very high diagnostic accuracy in differentiating benign from malignant lesions, detectability of tumors of nonhepatocellular origin is increased significantly and direct assessment of treatment success with minimally invasive tumor ablative interventions in the liver is possible. The active principle of ultrasound contrast agents, examination technique as well as distinguishing features and appearance of various, frequently observed focal liver lesions are illustrated by cases from our department.