Behavioural and psychological symptoms of dementia in Down syndrome: Early indicators of clinical Alzheimer's disease?

Behavioural and Psychological Symptoms of Dementia (BPSD) are a core symptom of dementia and are associated with suffering, earlier institutionalization and accelerated cognitive decline for patients and increased caregiver burden. Despite the extremely high risk for Down syndrome (DS) individuals to develop dementia due to Alzheimer's disease (AD), BPSD have not been comprehensively assessed in the DS population. Due to the great variety of DS cohorts, diagnostic methodologies, sub-optimal scales, covariates and outcome measures, it is questionable whether BPSD have always been accurately assessed. However, accurate recognition of BPSD may increase awareness and understanding of these behavioural aberrations, thus enabling adaptive caregiving and, importantly, allowing for therapeutic interventions. Particular BPSD can be observed (long) before the clinical dementia diagnosis and could therefore serve as early indicators of those at risk, and provide a new, non-invasive way to monitor, or at least give an indication of, the complex progression to dementia in DS. Therefore, this review summarizes and evaluates the rather limited knowledge on BPSD in DS and highlights its importance and potential for daily clinical practice

Competitive tendering and deregulation in the British bus

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How to make ecological models useful for environmental management

Understanding and predicting the ecological consequences of different management alternatives is becoming increasingly important to support environmental management decisions. Ecological models could contribute to such predictions, but in the past this was often not the case. Ecological models are often developed within research projects but are rarely used for practical applications. In this synthesis paper, we discuss how to strengthen the role of ecological modeling in supporting environmental management decisions with a focus on methodological aspects. We address mainly ecological modellers but also potential users of modeling results. Various modeling approaches can be used to predict the response of ecosystems to anthropogenic interventions, including mechanistic models, statistical models, and machine learning approaches. Regardless of the chosen approach, we outline how to better align the modeling to the decision making process, and identify six requirements that we believe are important to increase the usefulness of ecological models for management support, especially if management decisions need to be justified to the public. These cover: (i) a mechanistic understanding regarding causality, (ii) alignment of model input and output with the management decision, (iii) appropriate spatial and temporal resolutions, (iv) uncertainty quantification, (v) sufficient predictive performance, and (vi) transparent communication. We discuss challenges and synthesize suggestions for addressing these points. © 2019 The Author(s)This paper was initialized during a special session on Ecological Modelling at the 10th Symposium for European Freshwater Science 2017 ( http://www.sefs10.cz/ ) and further developed during the AQUACROSS project, funded by European Union's Horizon 2020 research and innovation programme (Grant agreement No. 642317 ). SD, SDL and MF were partly funded by the “GLANCE” project (Global Change Effects in River Ecosystems; 01 LN1320A) through the German Federal Ministry of Education and Research ( BMBF ). SDL has received additional funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 748625 . JML acknowledges the support of the Spanish Government through María de Maeztu excellence accreditation 2018–2021 (Ref. MDM-2017-0714 )

5-HT7 receptors in Alzheimer's disease

Even though the involvement of serotonin (5-hydroxytryptamine; 5-HT) and its receptors in Alzheimer’s disease (AD) is widely accepted, data on the expression and the role of 5-HT7 receptors in AD is relatively limited. Therefore, the objective of the present work was to study the expression of serotonergic 5-HT7 receptors in postmortem samples of AD brains and correlate it with neurotransmitter levels, cognition and behavior. The study population consisted of clinically well-characterized and neuropathologically confirmed AD patients (n = 42) and age-matched control subjects (n = 18). Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and high-performance liquid chromatography were performed on Brodmann area (BA) 7, BA10, BA22, BA24, hippocampus, amygdala, thalamus and cerebellum to measure mRNA levels of 5-HT7 receptors (HTR7), as well as the concentrations of various monoamine neurotransmitters and their metabolites. Decreased levels of HTR7 mRNA were observed in BA10. A significant association was observed between HTR7 levels in BA10 and BEHAVE-AD cluster B (hallucinations) (rs(28) = 0.444, P < 0.05). In addition, a negative correlation was observed between HTR7 levels in BA10 and both MHPG concentrations in this brain region (rs(45) = -0.311; P < 0.05), and DOPAC levels in the amygdala (rs(42) = -0.311; P < 0.05). Quite sur- prisingly, no association was found between HTR7 levels and cognitive status. Altogether, this study supports the notion of the involvement of 5-HT7 receptors in psychotic symptoms in AD, suggesting the interest of testing antagonist acting at this receptor to specifically treat psychotic symptoms in this illness

Impact of wheat aleurone on biomarkers of cardiovascular disease, gut microbiota and metabolites in adults with high body mass index: a double‑blind, placebo‑controlled, randomized clinical trial

Purpose Aleurone is a cereal bran fraction containing a variety of beneficial nutrients including polyphenols, fibers, minerals and vitamins. Animal and human studies support the beneficial role of aleurone consumption in reducing cardiovascular disease (CVD) risk. Gut microbiota fiber fermentation, polyphenol metabolism and betaine/choline metabolism may in part contribute to the physiological effects of aleurone. As primary objective, this study evaluated whether wheat aleurone supplemented foods could modify plasma homocysteine. Secondary objectives included changes in CVD biomarkers, fecal microbiota composition and plasma/urine metabolite profiles. Methods A parallel double-blind, placebo-controlled and randomized trial was carried out in two groups of obese/overweight subjects, matched for age, BMI and gender, consuming foods supplemented with either aleurone (27 g/day) (AL, n = 34) or cellulose (placebo treatment, PL, n = 33) for 4 weeks. Results No significant changes in plasma homocysteine or other clinical markers were observed with either treatment. Dietary fiber intake increased after AL and PL, animal protein intake increased after PL treatment. We observed a significant increase in fecal Bifidobacterium spp with AL and Lactobacillus spp with both AL and PL, but overall fecal microbiota community structure changed little according to 16S rRNA metataxonomics. Metabolomics implicated microbial metabolism of aleurone polyphenols and revealed distinctive biomarkers of AL treatment, including alkylresorcinol, cinnamic, benzoic and ferulic acids, folic acid, fatty acids, benzoxazinoid and roasted aroma related metabolites. Correlation analysis highlighted bacterial genera potentially linked to urinary compounds derived from aleurone metabolism and clinical parameters. Conclusions Aleurone has potential to modulate the gut microbial metabolic output and increase fecal bifidobacterial abundance. However, in this study, aleurone did not impact on plasma homocysteine or other CVD biomarkers. Trial Registration The study was registered at ClinicalTrials.gov (NCT02067026) on the 17th February 2014

Assessing the psychometric properties and the perceived usefulness of the BasisRaadsOnderzoek (BARO) as a first-line screening instrument for juvenile offenders

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to investigate the psychometric properties and the perceived usefulness of the BARO (Dutch: BAsisRaadsOnderzoek; Protection Board Preliminary Examination of Juvenile Suspects). The BARO is a first-line screening instrument for the identification of psychiatric disorders, adverse environmental factors, and levels of (dys)function in adolescent offenders (age 12 to 18), to be used by social workers of the Child Protection Board (CPB) following a police arrest.</p> <p>Method</p> <p>CPB workers administered the BARO to 295 juvenile offenders (91% boys, 9% girls). A subgroup of 66 offenders (89% boys, 11% girls) underwent an elaborate diagnostic assessment by forensic psychologists and psychiatrists. Using these assessments the most relevant psychometric properties of the BARO were studied. The perceived usefulness was studied using questionnaires to be filled in by the CPB social workers.</p> <p>Results</p> <p>The internal consistency of the instrument was sufficient to good, the concurrent validity of the CPB social workers applying the BARO and the forensic experts carrying out the comprehensive diagnostic assessment was strong, the discriminatory value of the instrument was moderate to strong, and the perceived usefulness of the instrument was evaluated as good to very good by the majority of the CPB workers.</p> <p>Discussion</p> <p>The BARO has sufficient to good psychometric properties including moderate to strong discriminatory value and is considered a good screening instrument by the CPB social workers. In conclusion, the BARO seems to be a very promising first-line screening instrument to identify psychiatric and psychosocial problems in young offenders.</p

Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early-onset Alzheimer's disease

Introduction: People with Down syndrome (DS) are at high risk for Alzheimer's disease (AD). Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS. Methods: Noradrenaline, adrenaline, and their metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; and serotonin and its metabolite 5-hydroxyindoleacetic acid were quantified in 15 brain regions of DS without AD (DS, n = 4), DS with AD (DS+AD, n = 17), early-onset AD (EOAD, n = 11) patients, and healthy non-DS controls (n = 10) in the general population. Moreover, monoaminergic concentrations were determined in cerebrospinal fluid (CSF)/plasma samples of DS (n = 37/149), DS with prodromal AD (DS+pAD, n = 13/36), and DS+AD (n = 18/40). Results: In brain, noradrenergic and serotonergic compounds were overall reduced in DS+AD versus EOAD, while the dopaminergic system showed a bidirectional change. For DS versus non-DS controls, significantly decreased MHPG levels were noted in various brain regions, though to a lesser extent than for DS+AD versus EOAD. Apart from DOPAC, CSF/plasma concentrations were not altered between groups. Discussion: Monoamine neurotransmitters and metabolites were evidently impacted in DS, DS+AD, and EOAD. DS and DS+AD presented a remarkably similar monoaminergic profile, possibly related to early deposition of amyloid pathology in DS. To confirm whether monoaminergic alterations are indeed due to early amyloid β accumulation, future avenues include positron emission tomography studies of monoaminergic neurotransmission in relation to amyloid deposition, as well as relating monoaminergic concentrations to CSF/plasma levels of amyloid β and tau within individuals

Adolescent suicidal ideation: a comparison of incarcerated and school-based samples

and risk-taking behavior. RESULTS: Suicidal ideations during the past year were reported by 21.5% of detained males, compared to 6.7% in the general population. In females, 58.1% of detained individuals reported suicidal thoughts during the past year, compared to 14.4% of the general population. In girls and boys from the general population, both internalizing and externalizing problems were higher in suicidal ideators than in non-suicidal youth, while in the detention group mainly internalizing problems were higher in suicidal ideators. When comparing detention suicidal ideators with those from the general population, male suicidal ideators scored higher on delinquency, while detained female suicidal ideators also scored higher on posttraumatic stress, but lower on prosocial beliefs. LIMITATIONS: Information used in this study was solely based on self-report measures only and limited to Flemish adolescents. CONCLUSION: Since suicidal ideation is a frequent problem in detained youth, adequate recognition and treatment seems clinically relevant. While both internalizing and externalizing psychopathology may be an indicator of suicidal ideation in the general population, internalizing problems may be the main clinical predictor in detained yout

The Validity of d′ Measures

Subliminal perception occurs when prime stimuli that participants claim not to be aware of nevertheless influence subsequent processing of a target. This claim, however, critically depends on correct methods to assess prime awareness. Typically, d′ (“d prime”) tasks administered after a priming task are used to establish that people are unable to discriminate between different primes. Here, we show that such d′ tasks are influenced by the nature of the target, by attentional factors, and by the delay between stimulus presentation and response. Our results suggest that the standard d′ task is not a straightforward measure of prime visibility. We discuss the implications of our findings for subliminal perception research