What Characterizes Depression in Old Age? Results from the Bruneck Study.

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.

Extracellular matrix proteomics identifies molecular signature of symptomatic carotid plaques.

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.

Consistency of "Probable RBD" Diagnosis with the RBD Screening Questionnaire: A Follow-up Study.

INTRODUCTION: The 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. METHODS: Probable RBD was assessed by RBDSQ in 2008 and in 2010 in the Bruneck Study Cohort, with participants aged ≥60 years. RESULTS: A 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). CONCLUSIONS: We 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.

Probable RBD and association with neurodegenerative disease markers: A population-based study.

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.

Lipidomics profiling and risk of cardiovascular disease in the prospective population-based Bruneck study.

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.

Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study cohort): a population-based study.

BACKGROUND: There is emerging awareness that movement disorders rank among the most common neurological diseases. However, the overall burden of these disorders in the general community is not well defined. We sought to assess the prevalence of all common categories of movement disorders in a population, accounting for sex differences and age trends. METHODS: As part of an ongoing prospective population-based study of carotid atherosclerosis and stroke risk (the Bruneck Study), a total of 706 men and women aged 50-89 years underwent a thorough neurological assessment. The diagnosis of movement disorders and ratings for disease severity were based on standard criteria and scales. Prevalences were estimated from logistic regression models (regression-smoothed rates) and standardised to the age and sex structure of the general community. FINDINGS: The prevalence of all common categories of movement disorders was 28.0% (95% CI 25.9-30.1). Proportions in men (27.6% [95% CI 24.5-30.7]) and women (28.3% [25.5-31.2]) were closely similar and sharply increased with age (from 18.5% [15.0-22.0] in 50-59-year olds to 51.3% [44.9-57.7] in 80-89-year olds). Almost half of all patients (90/214) had moderate-to-severe disease expression, but only 7.0% (15/214) received standard drug treatment. Prevalence of tremor was 14.5%, followed by restless legs syndrome (10.8%), parkinsonism (7%), primary dystonia and secondary dystonia (1.8%), and chorea and tics (<1% each). A fifth of all movement disorders were diagnosed to be probably drug-induced. INTERPRETATION: There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community.