Background and Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates in a free and lipoprotein-bound form in plasma. This study sought to interrogate the novel relationship between PCSK9 and high-density lipoprotein (HDL).

INTRODUCTION:Depression in old age is associated with functional disabilities, cognitive impairment, lower self-rated quality of life, and increased mortality. The aim of the study was to reveal the prevalence of depression and to investigate the characteristics of patients treated with antidepressants. METHODS:We analyzed data from the Bruneck Study 2010. All participants completed a clinical examination, cognitive screening, the 30-item Geriatric Depression Scale (GDS) (cutoff score of>8 to define relevant depressive symptoms), and the World Health Organization quality of life questionnaire (WHO-QoL). Group differences were calculated using binary logistic regression analysis. RESULTS:Out of 456 participants (mean age of 73.1±8.2 years), 22.1% showed depressive symptoms, and out of these, 30% were taking antidepressants. The depressed group compared to the GDS ≤8 group showed significantly lower WHO-QoL (p<0.001) and Mini Mental State Examination (p=0.015) score. Further, 13% of the latter compared to the GDS>8 group received antidepressants, and these had a lower WHO-QoL score (p<0.033). DISCUSSION:Depressive symptoms are frequent in the elderly population. Our results confirm the negative influence of depressive symptoms on cognition and quality of life. Patients with somatic comorbidities are likely to receive more antidepressant medication.

BACKGROUND. The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the “vulnerable plaque,” necessitating an improved approach for predicting onset of symptoms. METHODS. We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques. Proteomics data were integrated with gene expression profiling of 121 carotid endarterectomies and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. Finally, epidemiological validation of candidate biomarkers was performed in two community-based studies. RESULTS. Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study. CONCLUSION. The identified 4-biomarker signature may improve risk prediction and diagnostics for the management of cardiovascular disease. Further, our study highlights the strength of tissue-based proteomics for biomarker discovery. FUNDING. UK: British Heart Foundation (BHF); King’s BHF Center; and the National Institute for Health Research Biomedical Research Center based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London in partnership with King’s College Hospital. Austria: Federal Ministry for Transport, Innovation and Technology (BMVIT); Federal Ministry of Science, Research and Economy (BMWFW); Wirtschaftsagentur Wien; and Standortagentur Tirol.

1 jci.org Introduction Atherosclerosis is a chronic and progressive disease of the arterial wall and the main underlying cause of stroke, myocardial infarction (MI), and cardiac death (1, 2). The evolution of atherosclerotic plaques involves endothelial dysfunction, accumulation of lipids and inflammatory cells, as well as remodeling of the extracellular matrix (ECM). Previously, atherosclerotic plaques were defined by histological appearance. Plaques with thin fibrous caps and a large lipid pool were classified as “vulnerable lesions.” Lipid-poor plaques rich in ECM with thick fibrous caps were considered “stable.” Recent findings have challenged this “vulnerable plaque” concept (3, 4): First, intravascular imaging revealed that only a small percentage of thin-capped plaques cause clinical events (4, 5). Second, shifts in risk factor profiles (e.g., smoking cessation) and widespread use of statins are associated with a change in histopathological appearance of atherosclerotic lesions: “vulnerable plaques” with large lipid pools are far less common (3). Instead, superficial plaque erosions may trigger more cardiovascular events (3, 4). BACKGROUND. The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histologyand imaging-based definitions of the “vulnerable plaque,” necessitating an improved approach for predicting onset of symptoms.

IntroductionThe aim of this study was to evaluate the consistency of probable RBD diagnosis with the RBD screening questionnaire (RBDSQ) assessed 2 years apart in a population-based study.MethodsProbable RBD was assessed by RBDSQ in 2008 and in 2010 in the Bruneck Study Cohort, with participants aged 60 years.ResultsA total of 437 participants completed the RBDSQ in 2008 and 2010. There were 29 (6.6%) and 23 (5.3%) participants with probable RBD in 2008 and in 2010, respectively. Only eight (1.8%) screened positive on both occasions. RBDSQ values 2 years apart showed low correlation with each other (Spearman rank coefficient r = 0.348, P < 0.001) and low agreement (intraclass correlation coefficient 0.388, P < 0.001).ConclusionsWe found low agreement between the two assessments. Possible explanations are the fluctuation of untreated RBD expression and the poor utility of the RBDSQ to detect RBD in the general population. Until further PSG validation of the RBDSQ in population-based studies, investigators must be aware of the inherent uncertainty of questionnaire-based RBD diagnosis.

BACKGROUND:The prevalence of rapid eye movement sleep behavior disorder (RBD) and its association with markers of neurodegeneration in the general population are poorly defined.METHODS:We assessed the prevalence of probable RBD defined by two validated questionnaires, the RBD Screening Questionnaire (RBDSQ) and the Innsbruck RBD-Inventory (RBD-I), and studied its associations with clinical and imaging markers for neurodegeneration in the Bruneck Study cohort aged 60 y or older.RESULTS:Of the 456 participants without Parkinson's disease, 4.6% (RBDSQ; 95%CI, 3.0%-7.0%) and 7.7% (RBD-I; 95%CI, 5.6%-10.5%) had probable RBD. Probable RBD diagnosed with either of the questionnaires was associated with hyposmia (trend; P < 0.1), anxiety (P < 0.05), depression (P < 0.05), antidepressant use (P < 0.05), and self-reported non-motor symptoms (P < 0.01), specifically, dribbling saliva, memory problems, apathy, concentration problems, and anxiety.CONCLUSIONS:Our findings may provide a basis for future studies intending to identify cohorts at risk for Lewy body diseases through screening of the general elderly population for RBD.

Background— The bulk of cardiovascular disease risk is not explained by traditional risk factors. Recent advances in mass spectrometry allow the identification and quantification of hundreds of lipid species. Molecular lipid profiling by mass spectrometry may improve cardiovascular risk prediction. Methods and Results— Lipids were extracted from 685 plasma samples of the prospective population-based Bruneck Study (baseline evaluation in 2000). One hundred thirty-five lipid species from 8 different lipid classes were profiled by shotgun lipidomics with the use of a triple-quadrupole mass spectrometer. Levels of individual species of cholesterol esters (CEs), lysophosphatidylcholines, phosphatidylcholines, phosphatidylethanolamines (PEs), sphingomyelins, and triacylglycerols (TAGs) were associated with cardiovascular disease over a 10-year observation period (2000–2010, 90 incident events). Among the lipid species with the strongest predictive value were TAGs and CEs with a low carbon number and double-bond content, including TAG(54:2) and CE(16:1), as well as PE(36:5) ( P =5.1×10 −7 , 2.2×10 −4 , and 2.5×10 −3 , respectively). Consideration of these 3 lipid species on top of traditional risk factors resulted in improved risk discrimination and classification for cardiovascular disease (cross-validated ΔC index, 0.0210 [95% confidence interval, 0.0010-0.0422]; integrated discrimination improvement, 0.0212 [95% confidence interval, 0.0031-0.0406]; and continuous net reclassification index, 0.398 [95% confidence interval, 0.175-0.619]). A similar shift in the plasma fatty acid composition was associated with cardiovascular disease in the UK Twin Registry (n=1453, 45 cases). Conclusions— This study applied mass spectrometry-based lipidomics profiling to population-based cohorts and identified molecular lipid signatures for cardiovascular disease. Molecular lipid species constitute promising new biomarkers that outperform the conventional biochemical measurements of lipid classes currently used in clinics.

Movement DisordersVolume 27, Issue 9 p. 1194-1196 Letters: New Observations Is transcranial sonography useful to distinguish drug-induced parkinsonism from Parkinson's disease?†‡§ Philipp Mahlknecht MD, Philipp Mahlknecht MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorHeike Stockner MD, Heike Stockner MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorStefan Kiechl MD, Stefan Kiechl MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorJohann Willeit MD, Johann Willeit MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorVerena Rastner MD, Verena Rastner MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorArno Gasperi MD, Arno Gasperi MD Department of Neurology, Hospital of Bruneck, Bruneck, ItalySearch for more papers by this authorGregor Rungger MD, Gregor Rungger MD Department of Neurology, Hospital of Bruneck, Bruneck, ItalySearch for more papers by this authorWerner Poewe MD, Werner Poewe MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorKlaus Seppi MD, Corresponding Author Klaus Seppi MD [email protected] Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaDepartment of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this author Philipp Mahlknecht MD, Philipp Mahlknecht MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorHeike Stockner MD, Heike Stockner MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorStefan Kiechl MD, Stefan Kiechl MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorJohann Willeit MD, Johann Willeit MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorVerena Rastner MD, Verena Rastner MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorArno Gasperi MD, Arno Gasperi MD Department of Neurology, Hospital of Bruneck, Bruneck, ItalySearch for more papers by this authorGregor Rungger MD, Gregor Rungger MD Department of Neurology, Hospital of Bruneck, Bruneck, ItalySearch for more papers by this authorWerner Poewe MD, Werner Poewe MD Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this authorKlaus Seppi MD, Corresponding Author Klaus Seppi MD [email protected] Department of Neurology, Medical University Innsbruck, Innsbruck, AustriaDepartment of Neurology, Medical University Innsbruck, Innsbruck, AustriaSearch for more papers by this author First published: 12 June 2012 https://doi.org/10.1002/mds.25071Citations: 15 † Funding agencies: P.M. is sponsored by a research grant from the Medical University of Innsbruck (IFTZ 2007152). The follow-up investigation was supported by the Michael J. Fox Foundation. ‡ Relevant conflicts of interest/financial disclosures: Nothing to report. § Full financial disclosures and author roles may be found in the online version of this article. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume27, Issue9August 2012Pages 1194-1196 RelatedInformation

Background: Previous studies have yielded evidence of an enhanced risk of cardiovascular disease, especially stroke, among patients with migraine. Our understanding of the underlying mechanisms is far from complete. The aims of the present study were to investigate the potential association between migraine and atherosclerosis and to assess the risk of venous thromboembolism as a clinical surrogate for a procoagulant state in patients with migraine.Methods: The examination was part of the population-based Bruneck Study. During the 2005 evaluation, 574 participants aged 55-94 years underwent neurologic and laboratory examinations involving a standardized headache interview and scanning of the carotid and femoral arteries to evaluate presence, severity, and progression (2000-2005) of atherosclerosis.Results: A large number of well-founded and putative cardiovascular risk factors have emerged as being unrelated to migraine status. Prevalence, severity, and 5-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs. In fact, there was even a tendency for atherosclerosis to be less pronounced among patients with migraine, and for the intima-media thickness to be lower (p = 0.029). As a novel finding migraineurs faced a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs, age/sex-adjusted p = 0.031).Conclusion: This study is the first to compare the burden of atherosclerosis as quantified by high-resolution duplex ultrasound between migraineurs and nonmigraineurs in the general community, and provides solid evidence against the view that migraine predisposes to atherosclerosis. The higher risk for venous thromboembolism among migraineurs (prothrombotic state) awaits confirmation and elaboration in future research.

The aim of the current study was to estimate the prevalence of all primary headaches and cranial neuralgias in the general community. As part of the population-based Bruneck Study, 574 men and women aged 55–94 years underwent extensive neurological and laboratory examinations involving a standardized headache interview. In the Bruneck Study population the lifetime prevalence of all primary headaches combined and of cranial neuralgias was 51.7 and 1.6%, respectively. Tension-type headache (40.9%) and migraine (19.3%) emerged as the most common types of headache. In men and women aged 55–94 years the 1-year prevalence of primary headaches was high at 40.5%. In this age range headaches caused significant impairment of health-related quality of life. The Bruneck Study has confirmed the high lifetime prevalence of primary headaches and cranial neuralgias in the general population and provided first valid prevalence data for all primary headaches based on International Classification of Headache Disorders, 2nd edition criteria.

We hypothesized that the formation of foam cells and fatty streaks requires a postsecretory oxidative modification of lipoproteins that targets them for rapid uptake by macrophages. Lipid peroxidation may in part depend on the concentration of tissue iron, one of the major oxidants in vivo. We analyzed the relation between sonographically assessed carotid atherosclerosis and body iron stores in a population sample of 847 men and women aged 40 to 79 years. In a logistic regression analysis adjusting for age, sex, and all major vascular risk markers, ferritin emerged as one of the strongest indicators of carotid artery disease in both sexes (40 to 59 R ecent advances in understanding vascular lipid metabolism have yielded new insights into the mechanisms that determine endothelial injury and plaque development. In particular, the postseCTetory modification of lipoproteins has attracted increasing attention. Oxidative changes in the surface structure of low-density lipoproteins enhance the affinity to macrophage scavenger receptors, giving rise to the formation of foam cells and fatty streaks.Prominent iron stores may promote lipid peroxidation and accelerate atherogenesis and cardiovascular disease. This hypothesis recently received empirical support from a large population study (Kuopio Ischaemic Heart Disease Risk Factor Study) that demonstrated an enhanced risk of myocardial infarction in middle-aged men with elevated concentrations of serum ferritin. These findings, however, do not necessarily imply a causal role of iron in atherogenesis. Enhanced reperfusion injury, direct cardiotoxicity of high myocardial iron deposits, vasospastic events, and increased blood viscosity may also be significant. We designed the current study to investigate the relation between sonographically assessed carotid atherosclerosis and body iron stores as estimated by serum ferritin. We also investigated physiologically normal iron status and addressed sex differences in the amount of body iron and the manifestation of atherosclerotic vascular disease. Received November 30, 1993; revision accepted June 29, 1994. From the Department of Neurology (S.K., F.A., F.G., F.S., J.W.) and Department of Laboratory Medicine (EJ.), University Ginic Innsbruck (Austria), and the Department of Internal Medicine, Hospital of Bruneck (G.E., A.M., G.R., F.O.) (Italy). Correspondence to Dr J. Willeit, Department of Neurology, University of Innsbruck, AnichstraBe 35, A-6020 Innsbruck, Austria. years; odds ratio, 1.54 per 100 /xg/L; P<.001). The predictive significance of ferritin was found to be synergistic with that of hypercholesterolemia. Variations in body iron stores between sexes may partly explain evident sex differences in the expression of carotid atherosclerosis. In the elderly (£60 years) the predictive significance of ferritin was found to decrease parallel to that of apolipoprotein B. The current study suggests a possible role of body iron in early atherogenesis. (ArUriosder Thromb. 1994;14:1625-1630.)